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Although the remote collection of patient-reported outcomes (PROs) has been proven to be feasible and effective in breast cancer in several studies, barriers to the wide adoption of the practice in the US persist, according to Gabrielle Rocque, MD.

“To me, we’ve answered the question as to whether remote symptom monitoring works; that is a definitive yes,” Rocque said in an interview with 

. “The real questions are about how we implement this at large scale. How do we make sure we do this in a way that is patient and provider friendly? How do we tailor and customize [these interventions] to have them fit into the local context and fit for that patient and provider? There’s a lot of ongoing implementation work in this space.”

Rocque is an associate professor of medicine in the divisions of hematology

and oncology and gerontology, geriatrics, and palliative care at the University of Alabama at Birmingham.

During the 2024 San Antonio Breast Cancer Symposium, Rocque was a panel discussant for a presentation by Maria M. Karsten, MD, a managing senior physician at the Breast Center of the Charité-Universitätsmedizin Berlin in Germany, on PRO B, an alert-based PRO monitoring system.

 The PRO B system combined a weekly survey sent to patients’ smartphones, including questions from The European Organization for Research and Treatment of Cancer Computerized Adaptive Test Core item banks with an automated system, which alerted the treating center in the event of deteriorating PRO values, which then connected with the patient within 48 hours to address the reported symptoms. Patients in the control arm received PRO questionnaires sent to their smartphone every 3 months and were not connected to the alert monitoring system.

The PRO B trial included patients from 52 centers in Germany treated between May 2021 and June 2023. Patients were randomly assigned 1:1 to the PRO B intervention arm (n = 456) or the control arm (n = 453). The primary end point was patient-reported fatigue at 6 months after random assignment; secondary end points included physical functioning, quality of life, and overall survival (OS).

At baseline, the mean fatigue T-scores in the intervention and control arms were 57.6 and 60.2, respectively. The mean 6-month fatigue T-score in the intervention group was 53.2 compared with 58.7 in the control group. The respective scores at 12 months were 53.9 and 59.2.

Patients in the intervention group achieved a 12-month OS rate of 87.6% compared with 84.7% among patients in the control group (adjusted HR, 0.71; 95% CI, 0.51-0.99; P = .043). Patients with visceral metastases in the intervention (n = 66) and control (n = 68) arms experienced 12-month OS rates of 88.5% and 82.7%, respectively (adjusted HR, 0.51; 95% CI, 0.13-2.00; P = .331). The respective rates among patients with triple-negative breast cancer in the interventional (n = 36) and control (n = 49) arms were 88.5% and 82.7%, respectively (adjusted HR, 0.61; 95% CI, 0.24-1.53; P = .289). Patients with estrogen receptor–positive disease experienced a 12-month OS rate of 88.5% in the interventional arm (n = 287) vs 82.7% in the control arm (n = 269; adjusted HR, 0.71; 95% CI, 0.48-1.04; P = .076).

“This presentation was exciting because it was breast cancer focused, and it brought to a breast cancer audience some of the knowledge of [this type of] intervention,” Rocque said. “Most of us in the health care delivery and health services space are very familiar with this body of work, but the breast cancer world and [those involved] in breast cancer trials are not necessarily as familiar with this. This is a place where we have a win-win. If you’re a clinical trialist, you should watch your patients via remote symptom monitoring because they’re going to have fewer symptoms potentially [fewer] adverse effects, and be on the drug longer.”

Rocque noted that the value of remote PRO monitoring in various tumor types has been demonstrated across multiple other studies. In a 2017 study, Basch et al demonstrated that patients who received PRO monitoring via an automated email system experienced a significant OS benefit compared with those who received usual care; the median OS was 31.2 months (95% CI, 24.5-39.6) vs 26.0 months (95% CI, 22.1-30.9), respectively (HR, 0.83; 95% CI, 0.70-0.99; P = .04).

Additionally, data from the phase 3 CAPRI trial (NCT02828462) showed that patients with metastatic disease who were being treated with oral anticancer agents who participated in a nurse navigator–led symptom follow-up system with a smartphone-based symptom monitoring system received a higher treatment dose intensity compared with those who received usual care.

 Those who received the intervention also reported an improved patient experience, reduced hospitalization times, and fewer grade 3 or higher toxicities compared with those who did not.

Tackling Roadblocks to Widespread Implementation

Despite the proven ability of remote symptom monitoring to improve patient outcomes, widespread uptake of the technology in the US has lagged, Rocque said. She noted that the current payment models are not equipped to support widespread remote symptom monitoring due to a historic lack of billing codes for the technology. Additionally, hospital staffing and support staff are often not set up to address the increased call volumes that result from this type of symptom monitoring. There are also outdated electronic health record systems that need to be addressed, administrative level buy-in challenges, and patient comfortability issues with the technology, she said.

“A big piece [to address these barriers] is changing the payment models to include remote symptom monitoring,” Rocque said. “Sharing information on best practices is also helpful. Pressure from patients that this is something they want is a differentiator. We want to be able to show that this is important and [leads to] better outcomes. More research on implementation is needed to move the field forward. My ideal scenario is that someday we get to a point where we have a more nuanced idea of who exactly needs what based on their symptoms and treatment.”

Rocque is collaborating with Ethan Basch, MD, MSc, of UNC Health in Chapel Hill, North Carolina, on a Patient-Centered Outcomes Research Institute (PCORI)–funded project that is aiming to make the use of electronic PROs a routine aspect of care in the US.

 The project is adding software to the electronic health record that collects PROs and alerts health care staff when patients experience worsening symptoms. It will also educate patients on the use of electronic PROs, train clinical staff on the use of electronic PROs, and provide resources to help clinics implement the technology.

The study will include more than 34,000 patients and 7800 clinical staff members. The PCORI project was initiated in November 2023 and is slated to end in February 2030.

“[Future research should examine] how we can start tailoring these surveys to individual, personalized patient needs,” Rocque said.

Karsten MM, Gebert P, Pross T, et al. Evaluating the effect of an alert-based patient-reported outcome monitoring compared with usual care in metastatic breast cancer patients. Presented at: San Antonio Breast Cancer Symposium; December 10-13, 2024; San Antonio, TX. Abstract GS1-06.

Basch E, Deal AM, Dueck AC, et al. Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. JAMA. 2017;318(2):197-198. doi:10.1001/jama.2017.7156

Mir O, Ferrua M, Fourcade A, et al. Digital remote monitoring plus usual care versus usual care in patients treated with oral anticancer agents: the randomized phase 3 CAPRI trial. Nat Med. 2022;28(6):1224-1231. doi:10.1038/s41591-022-01788-1

Using electronic patient-reported outcomes (ePROs) to monitor symptoms during cancer treatment. Patient-Centered Outcomes Research Institute. Accessed March 24, 2025. bit.ly/41SBTZ6

Articles

Remote collection of patient-reported outcomes (PROs) in breast cancer is effective but faces adoption barriers in the US. Implementation challenges include payment models, staffing, and outdated systems. The PRO B trial demonstrated improved fatigue scores and overall survival with alert-based PRO monitoring. Despite proven benefits, widespread uptake is hindered by lack of billing codes and administrative challenges. Efforts to integrate electronic PROs into routine care are underway, with projects aiming to enhance patient and provider engagement, and tailor interventions to individual needs.

Oncology Business Management 

Barriers in utilizing remote collection of patient-reported outcomes persist, although it has been proven to be effective in breast cancer.

Researchers Address the Barriers to Remote Breast Cancer Symptom Monitoring in the US

Breast cancer remains the most prevalent cancer among women in the US. In 2024, approximately 310,720 new cases of invasive breast cancer and 56,500 cases of ductal carcinoma in situ were diagnosed among women across the country. Additionally, approximately 42,250 women died from this disease.

Metastatic breast cancer poses significant treatment challenges. Approximately 15% to 20% of cases of metastatic disease are HER2 positive, which promotes cancer cell growth.

The treatment paradigm for metastatic HER2-positive breast cancer typically involves targeted therapies such as trastuzumab (Herceptin) and pertuzumab (Perjeta), often in combination with chemotherapy, to inhibit the HER2 protein and slow disease progression.

 The antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) displayed a high response rate of 79.7% (95% CI, 74.3%-84.4%) and a median investigator-assessed progression-free survival of 25.1 months (95% CI, 22.1-not estimable) in patients with HER2-positive metastatic breast cancer in the second-line setting (n = 261), according to data from the phase 3 DESTINY-Breast03 trial (NCT03529110).

Small-molecule HER2 inhibitors, such as tucatinib (Tukysa), neratinib (Nerlynx), and lapatinib (Tykerb), have also shown positive results and intracranial responses when combined with chemotherapy (with/without trastuzumab) or endocrine therapy.

 Despite these advances, the response to treatment tends to be limited, and disease progression is inevitable. In addition, both the response rates and duration of response decrease as patients cycle through the lines of therapy. There remains a significant unmet need for better treatments that not only prolong life but also preserve the quality of life in women with metastatic disease.

Developing a Potential New Treatment Option for Patients With Breast Cancer

At the Barbara Ann Karmanos Cancer Institute, a National Cancer Institute–Designated Comprehensive Cancer Center in Detroit, Michigan, the Bone Marrow and Stem Cell Transplant, Hematologic Oncology, and Multiple Myeloma and Amyloidosis Multidisciplinary Teams (MDTs) have helped drive many treatment advancements in cellular immune therapies for cancers. This includes chimeric antigen receptor (CAR) T-cell therapy, which has revolutionized the treatment of certain hematologic malignancies, including specific types of leukemia and lymphoma, and has significantly improved response rates for these diseases.

 This personalized immunotherapy involves modifying a patient’s T cells, which are an integral part of the immune system, to recognize and attack cancer cells.

Karmanos Cancer Institute offers all approved CAR T-cell therapies for non-Hodgkin lymphoma, acute lymphoblastic leukemia, and multiple myeloma. The institute also supports research into new treatment indications for which CAR T-cell therapy could be used. I, along with other principal investigators at Karmanos, am now exploring the application of CAR T-cell therapy for solid tumors, including breast cancer, which presents a set of new challenges due to tumor microenvironment and antigen heterogeneity.

One such clinical study open at Karmanos is investigating the safety and efficacy of cellular immunotherapy in combination with targeted therapy for the treatment of solid tumors. In a phase 1 trial (NCT06241456), we are evaluating FT825/ONO-8250, an induced pluripotent stem cell–derived off-the-shelf CAR T-cell product targeting HER2-positive and other advanced solid tumors in combination with trastuzumab or cetuximab (Erbitux). Early data from this trial indicate no dose-limiting toxicities and no significant adverse effects, such as cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, or graft-vs-host disease. These findings suggest a promising avenue for developing effective cellular therapies for solid tumors, including HER2-positive breast cancer. The ongoing study enrolls participants with advanced HER2- and EGFR-expressing solid tumors such as breast, gastrointestinal, gynecologic, and head and neck cancers.

Karmanos specialists have experience in providing commercially approved and investigational cellular therapies. We work closely with investigators, developing novel strategies to make this therapy safer, developing pathways toward new indications, and ensuring more accessibility to CAR T-cell therapy. With our robust clinical trials program and experienced team, we are committed to further improving outcomes for patients who are candidates for these therapies and overcoming associated challenges. We look forward to witnessing how this therapy can transform the standard of care for many of our patients in the future.

Hadeel Assad, MD, is a medical oncologist specializing in breast cancer. She is the co-leader of the Breast Cancer Multidisciplinary Team (MDT), a member of the Phase I Clinical Trials MDT, and a scientific member of the Population Studies and Disparities and the Molecular Therapeutics Research Programs at Karmanos Cancer Institute in Detroit, Michigan.

Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. 

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Giaquinto AN, Sung H, Newman LA, et al. Breast cancer statistics 2024. 

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Swain SM, Miles D, Kim SB, et al; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. 

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Cortés J, Kim SB, Chung WP, et al; DESTINY-Breast03 Trial Investigators. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. 

. 2022;386(12):1143- 1154. doi:10.1056/NEJMoa2115022

Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. 

. 2020;382(7):597-609. doi:10.1056/NEJMoa1914609

Saura C, Oliveira M, Feng YH, et al; NALA Investigators. Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2- positive metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: phase III NALA Trial. 

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Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. 

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Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. 

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Schuster SJ, Bishop MR, Tam CS, et al; JULIET Investigators. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. 

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Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. 

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Fate Therapeutics highlights cancer-selective, HER2-targeting profile of FT825 / ONO-8250 CAR T-cell product candidate for treatment of advanced solid tumors at 2024 SITC Annual Meeting. News release. Fate Therapeutics. November 9, 2024. Accessed March 28, 2025. https://ir.fatetherapeutics.com/news-releases/news-release-details/fate-therapeutics-highlights-cancer-selective-her2-targeting

There remains a significant unmet need for better treatments that prolong life and preserve the quality of life in women with metastatic breast cancer.

The Move From Blood to Solid: Open Opportunities for CAR T-Cell Therapy in Solid Tumors

The mTOR inhibitors everolimus (Afinitor) and temsirolimus (Torisel) were both evaluated as part of combination regimens for patients with recurrent endometrial cancer with the goal of targeting the PI3K/ AKT/mTOR and RAS/RAF/MEK/ERK pathways, which are integral in endometrial tumorigenesis.1 However, although many doublet or triplet therapies have been examined in this setting, including regimens encompassing the aforementioned drugs, they have shown limited efficacy.

“At least 50% of patients with endometrial cancer have some abnormality in the PTEN/AKT pathway, [and] one of the ways we’ve tried to treat endometrial cancer is by targeting some of the steps along the [pathway],” Pamela T. Soliman, MD, MPH, said in an interview with OncologyLive. “The future [will revolve around a couple of questions]. How do we identify patients who would benefit from this strategy of targeted therapy? And what is the right combination to give them the maximum benefit but also make it with manageable toxicity?” 

The PI3K/AKT and RAS/RAF/MEK/ERK pathways involve mTOR as an important downstream player, making mTOR inhibitors a rational component of regimens for this patient population. Additionally, metformin induces metabolic changes and activates AMPK, which in turn inhibits the mTOR pathway, providing the baseline for Soliman and coinvestigators to examine the antidiabetic agent in combination with temsirolimus.

 Soliman added that because patients with endometrial cancer often have insulin resistance, addressing that and increasing the uptake of insulin in the peripheral circulation may inhibit the cancer.

Building on Findings with mTOR Inhibition Plus an Antidiabetic Agent

In a phase 1 study (NCT01529593), treatment with the combination of temsirolimus and metformin yielded an objective response rate (ORR) of 6% of patients with endometrial cancer (n = 2 of 33). Stable disease (SD) occurred in 39% of patients (n = 13 of 33), and 11 patients experienced SD for at least 4 months; these data translated to a clinical benefit rate (CBR) of 39%.

“When we’re looking at a population with recurrent disease [after] a number of different prior therapies, what I often tell patients is even if we can get the cancer control—even if it doesn’t shrink, but the cancer is able to be stabilized over time and they’re able to tolerate therapy—that still benefits them in the long run,” Soliman said. “If you combine the few responses and the higher percentage of SD, there were some patients who got benefit from this combination.”

Additionally, no grade 4 or 5 treatment-related adverse effects (TRAEs) occurred in patients treated with temsirolimus plus metformin. Grade 3 TRAEs included anemia and thrombocytopenia, which each occurred twice, and mucositis, fatigue, hypokalemia, weight loss, hypophosphatemia, increased aspartate aminotransferase levels, and increased alanine aminotransferase levels, which all occurred once. The most common any-grade TRAEs among the 32 patients who experienced toxicities in the phase 1 study were hypertriglyceridemia (44%), mucositis (41%), diarrhea (41%), anorexia (38%), anemia (31%), and nausea (25%).

“Although we were hoping for better responses…patients didn’t experience much toxicity,” Soliman said. “It was a tolerable [regimen], and some patients experienced benefit. With future studies, we’re trying to get more cancer control or higher response rates, but it’s important to also look at toxicity and tolerability because helping people live longer [and] making sure that they have a good quality of life is equally as important.”

A previous study also examined metformin in combination with the mTOR inhibitor everolimus and the hormone therapy letrozole (Femara).2 Data showed the triplet elicited a CBR of 50% in patients with recurrent endometrial cancer (n = 54) and a partial response (PR) rate of 28%, with 22% of patients experiencing SD. Additionally, the median progression-free survival was 5.7 months (95% CI, 3.0-8.1), and the median overall survival was 19.6 months (95% CI, 14.2-26.3). 

No patients experienced grade 5 AEs, and hypertriglyceridemia occurred at grade 4 in 1 patient. “With a lot of mTOR inhibitors, one of the AEs is hyperglycemia,” Soliman said. “We’ve seen in different studies of metformin that you can add the drug to other [agents] and it doesn’t increase toxicity very much; it’s a well-tolerated and safe drug. These studies were ongoing [at the time we started the phase 1 trial], but we had already added metformin in a different trial that was published a couple of years ago to the combination of everolimus and letrozole…. There seems to be some role in adding metformin, [but] I don’t think we’ve figured out perfectly where we can get the biggest benefit, or which patients would benefit the most.”

Additional Combinations Under the Microscope

As investigators believe metformin inhibits the mTOR pathway through upstream activation of 5’-AMPK, they combined it with the potent, selective adenosine triphosphate–competitive mTORC1/2 inhibitor sapanisertib in a phase 1 dose-escalation study (NCT03017833).3 Among 30 evaluable patients with solid tumors, 4 patients experienced a PR, which included 1 patient with endometrial cancer; 1 other patient with endometrial cancer was enrolled in the trial and experienced progressive disease. 

Furthermore, the AKT/mTOR inhibitor ibrilatazar (ABTL0812) was also examined in patients with advanced/recurrent endometrial cancer and stage III and IV squamous non–small cell lung cancer not amenable to radiation in the phase 1/2 ENDOLUNG trial (NCT03366480).4 The combined patient population (n = 38) achieved an ORR of 65.8% (95% CI, 52.0%-78.9%), which included a complete response rate of 13.2% and a PR rate of 52.6%. Notably, the SD rate was 34.2%, and no patients experienced progressive disease, translating to a 100% disease control rate. Investigators of the trial noted that the data warranted further confirmation in prospective, randomized trials.

Further Homing In on Rational Combinations

When asked where research should go next with mTOR inhibitors, Soliman noted, “We’re still trying to figure it out, and one [element] is patient identification. More and more with endometrial cancer, we’re using patients’ molecular subtypes or molecular classifications to guide cancer therapy. Which patients truly benefit from these medications? Since [conducting] this [phase 1] trial, newer-generation mTOR inhibitors, AKT inhibitors, [and] a lot of agents [have emerged] in ongoing trials. We’re also looking at [potential] combinations with other drugs. 

In addition to antiestrogen therapy, is there a role for [cyclin-dependent kinase] 4/6 inhibitors that also potentiate the same pathway?” Regarding molecular classification, a subgroup of patients with PI3K/ PTEN and RAS alterations who received temsirolimus plus metformin in the phase 1 study experienced SD.1 Investigators highlighted this as significant because approximately 22% of those with endometrial cancer have PIKC3A hyperactivity, approximately 42% to 54% of patients have PTEN mutations or repression, and 10% to 30% of patients have KRAS mutations. “In this patient population where we’re trying to give patients [with endometrial cancer] the best option, offering patients a clinical trial allows us to get a better idea of response rates and tolerability for a lot of these newer drugs,” Soliman said. “Here, it’s a priority for us to put patients on trials. It’s important wherever you’re practicing to consider clinical trials for these patients because there is an unmet need for women with endometrial cancer [who experience] recurrence.”

mTOR inhibitors, everolimus and temsirolimus, have been evaluated in combination regimens for recurrent endometrial cancer, targeting the PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways. Despite limited efficacy, these combinations, including metformin, show potential in stabilizing disease with manageable toxicity. A phase 1 study of temsirolimus and metformin reported a clinical benefit rate of 39% with no severe adverse effects. Further research is needed to identify patient subgroups that benefit most from these therapies and to explore additional combinations, including newer-generation mTOR and AKT inhibitors.

Combinations targeting PI3K/AKT/mTOR and MAPK/ERK pathways are under investigation to improve outcomes in patients with endometrial cancer.

Combinations Targeting PI3K/AKT/mTOR and MAPK/ERK Pathways Are Under Study in Endometrial Cancer

Guided approaches with circulating tumor DNA (ctDNA) have just begun to scratch the surface of showing prognostic and predictive abilities in colorectal cancer (CRC), and new data have further shed light on ctDNA’s role. Clinical trials demonstrated that ctDNA-guided approaches can reduce the use of chemotherapy without compromising outcomes in those with minimal residual disease (MRD)–positive disease, and that celecoxib (Celebrex) benefited these patients.

“The results continue to be consistent across [the board] whether it’s the CIRCULATE-Japan GALAXY trial [UMIN000039205], [the observational] BESPOKE study [NCT04264702] from the US, or other smaller studies—they all suggest that patients who have MRD assessment may benefit at least from a discussion about whether to [move forward with] or forgo treatment,” Tanios S. Bekaii-Saab, MD, said in an interview with 

. “Assessment of MRD has made its way into CRC, specifically in the earlier stages of the disease, but also more into oligometastatic disease. Now, the role continues to be explored further. Most of the data we’ve had so far, except [for from] a couple of studies, were from large observational studies.”

The final analysis of the BESPOKE CRC study subcohort was published in 2025 as the largest multicenter ctDNA study reported in the US to date. It revealed that ctDNA testing following surgery led to a change in adjuvant treatment for 1 out of 6 patients with stage II/III CRC.

 Additionally, the adjuvant plan was validated for most patients, and a benefit with adjuvant chemotherapy was solely observed in those with MRD-positive disease.

Furthermore, the phase 2/3, prospective NRG-G1008 (CIRCULATE-North America) study (NCT05174169) is currently ongoing to evaluate the role of ctDNA in risk stratification for escalation or de-escalation of adjuvant therapy in patients with resected colon cancer.

 Aggregate data are planned to be combined with those from CIRCULATE-JAPAN.

Examining New Readouts of Data that Further Explore ctDNA's Role

According to an updated analysis of the phase 3 CALGB/SWOG 80702 study (NCT01150045), ctDNA was highly prognostic for disease-free survival (DFS) and overall survival (OS) in patients with stage III colon cancer, and ctDNA positivity appeared to be predictive of the benefit of adjuvant therapy with celecoxib for DFS and OS.

 Primary findings showed that patients in the study who received the anti-inflammatory drug plus FOLFOX (fluorouracil, leucovorin, and oxaliplatin) vs FOLFOX and placebo did not experience a statistically significant difference in DFS (HR, 0.89; 95% CI, 0.76-1.03; stratified log-rank 

“[Although] this study was negative for celecoxib’s effect vs placebo following adjuvant therapy, there were hints that there was a small subgroup of patients who may benefit,” Bekaii-Saab explained. “In the follow-up [data], approximately less than half of the patients had enough material that they could assess their MRD [with], and those who had MRD-positive disease appeared to benefit from the addition of celecoxib vs those who did not.”

Patients in the ctDNA-positive group experienced an estimated 5-year OS rate of 61.6% (95% CI, 52.4%-72.4%) when given celecoxib (n = 99) compared with 39.9% (95% CI, 29.6%-53.8%) when given placebo (n = 74; HR, 0.58; 95% CI, 0.38-0.90; 

 = .0135). Additionally, those who were ctDNA negative and received celecoxib (n = 375) achieved an estimated 5-year OS rate of 91.8% (95% CI, 88.9%-94.7%) vs 91.3% (95% CI, 88.4%-94.3%) in the placebo arm (n = 392; HR, 0.86; 95% CI, 0.55-1.35; 

“The question is [whether that] would change our standard today,” Bekaii-Saab said. “Does it mean that patients who are MRD positive should be put on celecoxib? Celecoxib does come with its own toxicities. This study was a post hoc analysis, it was also a retrospective look, and less than half of the patients had materials [available to examine for MRD]. All these limitations have to be taken into account before making a decision, but I believe it’s worth discussing with patients. I’m finding myself at least having some level of discussion with patients about this [therapy], given the pros and the cons, and the fact that the data are still [developing] and further study [is needed].”

Another study that was reported as negative has posed important questions about the role of ctDNA in guiding decisions. The phase 3 ALTAIR study (NCT04457297) revealed that there was not a statistically significant DFS benefit when patients who were ctDNA positive following curative resection in the CIRCULATE-Japan study were given trifluridine/ tipiracil vs placebo.2 A numerical benefit was seen, as the median DFS was 9.30 months (95% CI, 7.92- 10.84) vs 5.55 months (95% CI, 4.17-7.33), respectively (HR, 0.79; 95% CI, 0.60-1.05; 

 = .107). Additionally, investigators found that the DFS benefit was clinically meaningful in patients who had resected stage IV disease.

“That [study] was a bit disappointing,” BekaiiSaab noted. “However, on the other side, one would ask the question: Is trifluridine/tipiracil the right agent? It is a fluoropyrimidine, and patients were already exposed to capecitabine. Does that make sense? Should we go more toward targeted approaches? [For example], if a patient has a BRAF V600E mutation, do we go to BRAF-targeted strategies, rather than just switch to another chemotherapy? That study, unfortunately, tells us that another chemotherapy may not cut it.”

Trying to Determine the Necessity of Adjuvant Chemotherapy

The phase 2 DYNAMIC study (ACTRN12615000381583) randomly assigned patients with resected stage II colon cancer to either standard management, which included adjuvant treatment decisions based on conventional clinicopathologic criteria, or ctDNA-guided management, which encompassed observation for those who were ctDNA negative and adjuvant chemotherapy for those who were ctDNA positive.

The 5-year relapse-free survival rate was 88.3% in the ctDNA arm (n = 294) vs 87.2% in the standard of care (SOC) arm (n = 147), confirming initial findings from the study that these patients could benefit from a ctDNA-guided approach, as the use of chemotherapy was reduced and survival outcomes were maintained.

Additional data from DYNAMIC showed the 5-year OS rates were 93.8% in the ctDNA arm vs 93.3% in the SOC arm (HR, 1.05; 95% CI, 0.47- 2.37; 

 = .887). Patients in the ctDNA arm who had ctDNA-negative disease (n = 246) experienced a 5-year OS rate of 95.3% compared with 85.6% in the ctDNA-positive group (n = 45; HR, 3.30; 95% CI, 1.20-9.05; 

 = .014). Investigators noted that most patients who are ctDNA positive following surgery can achieve ctDNA clearance with adjuvant chemotherapy and this is associated with positive outcomes. They added that although validation of these findings is needed, there could be potential to improve the precision of the ctDNA-informed approach by increasing variant number and incorporating ctDNA molecular burden.

Bekaii-Saab will discuss the use of ctDNA in the clinic and more at the 2025 International Symposium of Gastrointestinal Oncology conference, which he is cochairing.

 Slated for September 12 to 13, 2025, in Austin, Texas, the multidisciplinary meeting will comprehensively review the gastrointestinal cancer landscape and focus on examining the complex array of recent studies that are informing clinical practice. As the role of ctDNA continues to be examined, the conference will cover that aspect of care and more.

“Attendees [of] the conference will come out of it with what I hope is a clear understanding of the shifting landscape on a yearly basis. What they want to take home with them is one, what do I do for my patients after this conference? How can I change my practice in a way that’s positively affecting outcomes?” Bekaii-Saab noted. “The second is a clear understanding of what’s coming. What should I need? What should I continue to pay attention to and what may be a practice-changing element next year or the year after?”

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Bando H, Watanabe J, Kotaka M, et al. A randomized, doubleblind, phase III study comparing trifluridine/tipiracil (FTD/ TPI) versus placebo in patients with molecular residual disease following curative resection of colorectal cancer (CRC): the ALTAIR study. J Clin Oncol. 2025;43(suppl 4):LBA22. doi:10.1200/JCO.2025.43.4_suppl.LBA22

Shah PK, Aushev VN, Ensor J, et al. Circulating tumor DNA for detection of molecular residual disease (MRD) in patients (pts) with stage II/III colorectal cancer (CRC): final analysis of the BESPOKE CRC sub-cohort. J Clin Oncol. 2025;43(suppl 4):15. doi:10.1200/JCO.2025.43.4_suppl.15

Lieu CH, Yu G, Kopetz S, et al. NRG-GI008: colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-North America). J Clin Oncol. 2025;43(suppl 4):TPS310. doi:10.1200/JCO.2025.43.4_suppl.TPS310

Nowak JA, Shi Q, Twombly T, et al. Prognostic and predictive role of circulating tumor DNA (ctDNA) in stage III colon cancer treated with celecoxib: findings from CALGB (Alliance)/SWOG 80702. J Clin Oncol. 2025;43(suppl 4):LBA14. doi:10.1200/ JCO.2025.43.4_suppl.LBA14

In the colorectal cancer space, the role of ctDNA can help reduce the use of certain therapies. 

ctDNA Aids in Elucidating the Role of Select Therapies for CRC

Clinical trial updates presented during the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), including from the phase 3 CheckMate 9ER (NCT03141177) and COSMIC-313 (NCT03937219) studies, have further validated combination regimens as the first-line treatment for patients with advanced renal cell carcinoma (RCC). Because of the numerous options, investigators must carefully consider factors such as sarcomatoid features, disease risk status, and patient fitness when selecting from the current regimens.

“We have several clear ‘right answers’ when it comes to first-line [treatment] for patients with advanced RCC,” Elizabeth M. Wulff-Burchfield, MD, said. “My perspective is that not every efficacy outcome matters for every patient. [For example], in the beginning, if [a patient] is in visceral crisis, then the only outcome that matters is objective response rate [ORR]. It’s OK to let that guide us, but if we have more indolent disease, among other [factors], the possibility of a treatment-free interval can rise in our prioritization. It is [acceptable] to, in addition to knowing the data, prioritize some of the outcomes differently for different patients.”

 filmed during ASCO GU, expert investigators discussed significant updates in the RCC space from the meeting and beyond. They highlighted data from final analyses of CheckMate 9ER and COSMIC-313, discussed treatment selection considerations for patients with treatment-naive disease, and looked forward to results from clinical trials of the investigational agents HC-7366 and CBM588 in the frontline, second line, and beyond.

Nivolumab Forms Basis of Frontline IO Combinations

In first-line RCC, the FDA has approved nivolumab (Opdivo) as a component in 2 combination regimens.

 The first was in April 2018, when frontline nivolumab plus ipilimumab (Yervoy) was approved for patients with intermediate- or poor-risk advanced RCC. In January 2021, nivolumab plus cabozantinib (Cabometyx) was approved in the first line. The approvals were supported by findings from the phase 3 CheckMate 214 (NCT02231749) and CheckMate 9ER trials, respectively.

“We have all of these immunotherapy [IO]–based combinations approved in frontline RCC, but the one that revolutionized the field was [investigated in] CheckMate 214 because [that study] led to the approval of the first IO-based combination and, to date, the only IO/IO regimen in treatment-naive metastatic RCC,” 

At a median follow-up of 99.1 months (range, 91.0-107.3), longterm follow-up data from CheckMate 214 showed that patients who received nivolumab plus ipilimumab (n = 550) achieved a median overall survival (OS) of 52.7 months (95% CI, 45.8-64.5) vs 37.8 months (95% CI, 31.9-43.8) among 546 patients who received sunitinib (Sutent; HR, 0.72; 95% CI, 0.62-0.83).3 The 90-month OS rates were 35.1% vs 24.9%, respectively. The median progression-free survival (PFS) was 12.4 months (95% CI, 9.9-16.8) vs 12.3 months (95% CI, 9.8-15.2), respectively (HR, 0.88; 95% CI, 0.75-1.03).

“Perhaps the most interesting of the updates with this 8-year follow-up is in the favorable-risk population,” Ornstein added. “Originally, the [FDA] approval was for [patients at] intermediate and poor risk, and in the National Comprehensive Cancer Network [NCCN] guidelines, it was a preferred regimen in intermediate- and poor-risk [disease]. But with additional follow-up, we noticed the curves split at approximately 48 months in favor of nivolumab plus ipilimumab, with a median OS in the favorable-risk population of approximately 78 months for the patients who received nivolumab plus ipilimumab vs [approximately] 67 months for [patients at favorable risk who received sunitinib]. The HR was 0.82, although the CI crossed 1. However, it is now one of the preferred regimens in the NCCN guidelines, even in favorable-risk [disease].”

During ASCO GU, investigators presented findings from a post hoc analysis of CheckMate 214, which evaluated kidney injury molecule-1 (KIM1) as a prognostic and predictive biomarker in advanced RCC.

 Patients in both the investigational and control arms with high baseline KIM-1 levels experienced worse OS outcomes than those with low (HR, 2.74; 95% CI, 2.14-3.52) or medium (HR, 2.05; 95% CI, 1.62-2.59) baseline levels. Additionally, patients with high baseline KIM-1 in both arms also had worse PFS than patients with KIM-1 low (HR, 1.53; 95% CI, 1.18-1.97) or KIM-1 medium (HR, 1.57; 95% CI, 1.21-2.03) levels.

The panelists then discussed the final follow-up results of CheckMate 9ER presented during ASCO GU.

 At a median follow-up of 67.6 months (range, 60.2-80.2) in the intention-to-treat population, the median PFS in the nivolumab plus cabozantinib (n = 323) and sunitinib (n = 328) arms was 16.4 months (95% CI, 12.5-19.3) and 8.3 months (95% CI, 7.0-9.7), respectively (HR, 0.58; 95% CI, 0.49-0.70). The 60-month PFS rates were 13.6% and 3.6%, respectively. The median OS was 46.5 months (95% CI, 40.6-53.8) and 35.5 months (95% CI, 29.2-42.8), respectively (HR, 0.79; 95% CI, 0.65-0.96); the 60-month OS rates were 40.9% and 35.4%, respectively.

“Cabozantinib is one of the preferred TKIs [tyrosine kinase inhibitors], and in the refractory setting, we see a lot of combinations using it as a backbone,” 

Wulff-Burchfield added, “My overall impression [of the CheckMate 9ER update] was that it was very affirming to the data we have seen previously. This regimen is clearly superior to sunitinib [in terms of PFS]. One thing that stands out to me is how the hazard ratio is evolving in a different direction for patients with favorable-risk disease[compared with what we saw in] CheckMate 214. [These data] affirm that these are VEGF-driven tumors. Sunitinib is VEGF targeted, as is cabozantinib, even though cabozantinib has a broader mechanism of action. [These data] do not give us an obvious solution of a one-size-fits-all approach for our favorable-risk patients, but they certainly cement [this regimen] in the canon for first-line [therapy] in the overall population.”

In COSMIC-313, investigators added cabozantinib to ipilimumab and nivolumab in the frontline RCC setting.

 Patients were randomly assigned 1:1 to receive the triplet (n = 428) or placebo plus nivolumab and ipilimumab (n = 427). The primary end point was PFS per RECIST 1.1 and OS is the secondary end point.

Data from the final analysis presented during ASCO GU demonstrated that patients who received the triplet achieved a median PFS of 16.6 months (95% CI, 14.0-22.6) vs 11.2 months (95% CI, 9.3-14.0) for those in the placebo arm (HR, 0.82; 95% CI, 0.69-0.98). The 24-month PFS rates were 44% and 37%, respectively. The median OS was 41.9 months (95% CI, 34.8-47.9) with the triplet vs 42.0 months (95% CI, 34.9-53.1) with placebo (HR, 1.02; 95% CI, 0.85-1.23; P = .08366). The 36-month OS rate in both arms was 54%.

Following encouraging data from the phase 2 LITESPARK-003 (NCT03634540) and phase 1/2 LITESPARK-024 (NCT05468697) studies, which examined the HIF-2α inhibitor belzutifan (Welireg) in combination with cabozantinib or palbociclib (Ibrance), respectively, investigators have initiated the phase 3 LITESPARK-012 study (NCT04736706) to evaluate belzutifan as a triplet component.

 The trial is examining pembrolizumab (Keytruda) plus lenvatinib (Lenvima) with or without belzutifan or quavonlimab for the frontline treatment of patients with advanced clear cell RCC (ccRCC).

LITESPARK-012 is an open-label, multicenter study that will enroll approximately 1653 adults with advanced or metastatic ccRCC with measurable disease per RECIST 1.1 and a Karnofsky performance score of at least 70%. Eligible patients will be randomly assigned 1:1:1 to receive belzutifan plus pembrolizumab and lenvatinib (arm A); coformulated pembrolizumab and quavonlimab plus lenvatinib (arm B); or pembrolizumab plus lenvatinib (arm C). The coprimary end points are PFS and OS per RECIST 1.1 in arms A vs C and B vs C.

“We have learned a lot about how to manage adverse effects in a triplet arm,” 

, said. “We might see better exposure to the TKI and get better benefits. I’m excited to see [LITESPARK-012] read out. All of us want to see more cures in the frontline. There are a couple of [other] ongoing frontline trials that are about to start [enrolling] looking at triplet combinations of various immunotherapy regimens. I am looking forward to seeing those open and start enrolling.”

When selecting a treatment regimen in the frontline, Ornstein noted that patients with a visceral crisis who need an immediate response should usually be treated with an IO/TKI combination. He added that PD-L1 testing is largely not appropriate when selecting a frontline regimen; he often chooses the CheckMate 214 regimen for patients with sarcomatoid features because of poor historical outcomes with TKI therapy in this population.

“[In patients without] clear sarcomatoid histology, I’m not convinced that any of these IO/TKI regimens are better for any specific site of disease,” Ornstein explained. “Lenvatinib plus pembrolizumab has good data in [metastases of the] liver and bone, [as does] cabozantinib. We’re trying to tease out these subgroup analyses to see if we can determine which specific regimen can target which specific disease [type]. In summary, in sarcomatoid disease, I’m leaning toward an IO/IO combination. If patients need an [immediate] response, I’m giving an IO/TKI, focusing on [which] TKI [is appropriate for] a specific patient and for the favorable-risk population, I’m comfortable using all of them. I appreciate that ipilimumab plus nivolumab is now in the NCCN guidelines [in the favorable-risk group] because it makes it more available from an insurance perspective.”

Novel Agents Attract Attention in Multiple Disease Settings

Following their discussion of the frontline treatment landscape, the panelists shifted their conversation to highlight ongoing clinical trials of the investigational agents HC-7366 and CBM588. HC-7366 is a first-in-class GCN2 serine/threonine kinase activator, which investigators hypothesize can be combined with belzutifan to treat patients with ccRCC who experience disease progression.

 CBM588 is a live bacterial agent containing a strain of Clostridium butyricum, which has shown the potential to boost clinical outcomes in combination with immune checkpoint inhibition.

HC-7366 is being evaluated as monotherapy and in combination with belzutifan in patients with advanced or metastatic ccRCC in a phase 1b study (NCT06234605).8 To be eligible for the monotherapy arm, patients must have received 1 to 4 prior lines of therapy, including belzutifan or another HIF-2α inhibitor. In the combination arm, patients need to have received 1 to 3 prior lines of therapy for metastatic disease, including at least 1 anti–PD-1/anti– PD-L1 agent and a VEGF TKI. The primary end points are establishing the maximum tolerated and recommended phase 2 doses, and safety and tolerability. At the time of ASCO GU, enrollment was ongoing into 2 combination cohorts and a monotherapy cohort.

In another phase 1 trial (NCT06399419), CBM588 is being examined in combination with nivolumab and ipilimumab in adult patients with metastatic RCC with a clear cell or sarcomatoid component who have received no prior systemic therapy for RCC beyond 1 prior adjuvant/neoadjuvant therapy for resectable RCC.9 The primary objective is to determine the regimen’s safety and tolerability, and efficacy will be secondarily assessed.

CBM588 is also under evaluation in combination with cabozantinib and nivolumab in another phase 1 trial (NCT05122546); the study is enrolling patients with treatment-naive RCC with a clear cell, papillary, and/or sarcomatoid component.10 Patients were randomly assigned 2:1 to receive the triplet (n = 20) or cabozantinib plus nivolumab (n = 10).

Updated study data presented at ASCO GU showed that patients in the investigational arm achieved a median PFS of 19.7 months compared with 13.4 months in the control arm (HR, 0.74; 95% CI, 0.25-2.23; P = .59). Moreover, the ORRs were 84% and 20%, respectively. The study authors added that there were no additional toxicity signals and that the further development of CBM588 should be prioritized.

“We’ve seen data regarding antibiotic use for patients with RCC and how that impacts not only their gut microbiome but their efficacy outcomes as well,” Wulff-Burchfield said. “I’m looking forward to hearing more from [these studies of CBM588].”

FDA approves nivolumab plus ipilimumab combination for intermediate or poor-risk advanced renal cell carcinoma. FDA. April 16, 2018. Accessed March 13, 2025. https://www. fda.gov/drugs/resources-information-approved-drugs/fdaapproves-nivolumab-plus-ipilimumab-combination-intermediateor-poor-risk-advanced-renal-cell

FDA approves nivolumab plus cabozantinib for advanced renal cell carcinoma. FDA. January 22, 2021. Accessed March 13, 2025. https://www.fda.gov/drugs/resources-informationapproved-drugs/fda-approves-nivolumab-plus-cabozantinibadvanced-renal-cell-carcinoma

Tannir NM, Albigès L, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 8-year follow-up results of efficacy and safety from the phase III CheckMate 214 trial. Ann Oncol. 2024;35(11):1026-1038. doi:10.1016/j. annonc.2024.07.727

Xu W, Vemula SV, Motzer R, et al. Evaluation of circulating kidney injury marker-1 (KIM-1) as a prognostic and predictive biomarker in advanced renal cell carcinoma (aRCC): post-hoc analysis of CheckMate 214. J Clin Oncol. 2025;43(suppl 5):437. doi:10.1200/JCO.2025.43.5_suppl.437

Motzer R, Escudier B, Burotto M, et al. Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): final follow-up results from the CheckMate 9ER trial. J Clin Oncol. 2025;43(suppl 5):439. doi:10.1200/JCO.2025.43.5_suppl.439

Albiges L, Motzer R, Trevino S, et al. Cabozantinib (C) in combination with nivolumab (N) and ipilimumab (I) in previously untreated advanced renal cell carcinoma (aRCC): final results of COSMIC-313. J Clin Oncol. 2025;43(suppl 5):438. doi:10.1200/ JCO.2025.43.5_suppl.438

Choueiri TK, Powles T, Voss MH, et al. LITESPARK-012: pembrolizumab plus lenvatinib with or without belzutifan or quavonlimab for advanced renal cell carcinoma. Future Oncol. 2023;19(40):2631-2640. doi:10.2217/fon-2023-0283

Shah N, Bupathi M, Garmezy B, et al. A phase 1b, open-label, safety, tolerability, and efficacy study of HC-7366 in combination with belzutifan in patients with advanced or metastatic renal cell carcinoma (NCT06234605). J Clin Oncol. 2025;43(suppl 5):TPS609. doi:10.1200/JCO.2025.43.5_suppl.TPS609

Agarwal R, Ebrahimi H, Zengin ZB, et al. Dose finding study of CBM588 in combination with nivolumab and ipilimumab in patients with metastatic renal cell carcinoma: a phase I study. J Clin Oncol. 2025;43(suppl 5):TPS611. doi:10.1200/ JCO.2025.43.5_suppl.TPS611

Ebrahimi H, Meza LA, Dizman N, et al. Cabozantinib (cabo) and nivolumab (nivo) with or without CBM588 in patients with metastatic renal cell carcinoma: updated clinical outcomes of a phase I study. J Clin Oncol. 2025;43(suppl 5):543. doi:10.1200/ JCO.2025.43.5_suppl.543

Recent clinical trial updates from the 2025 ASCO GU Symposium have reinforced the efficacy of combination regimens as first-line treatments for advanced renal cell carcinoma (RCC). Key studies, including CheckMate 9ER and COSMIC-313, highlight the importance of considering patient-specific factors such as sarcomatoid features and disease risk status when selecting treatment. Nivolumab-based combinations remain pivotal, with long-term data supporting their use across various risk groups. Emerging trials are exploring novel agents like HC-7366 and CBM588, aiming to enhance treatment outcomes and address unmet needs in RCC management.

Peer Exchange

During an OncLive Peer Exchange filmed during ASCO GU, expert investigators discussed significant updates in the RCC space.

Combination Regimens Offer Options in Frontline RCC as Novel Agents Advance Through Pipeline

 his commentator could think of no better way to begin a brief discussion addressing the current unreality of cancer care finances in the US than to invoke the theme of Hans Christian Andersen’s famous childhood tale “The Emperor’s New Clothes.”

“Oh, how beautiful are our Emperor’s new clothes.... In fact, no one would admit that he could not see these clothes, which everyone seemed to think so beautiful, for fear he would be called a simpleton or unfit for his office.... ‘But the emperor has nothing on at all!’ said a little child.... ‘The child tells the truth,’ said the father. And so it was that what the child said was whispered from one to another until all knew, and they cried out altogether, ‘But he has nothing on at all!’ The Emperor felt very silly, for he knew that the people were right, but he thought, ‘The procession has started, and it must go on now!’ So, the Lords of the Bedchamber held their heads higher than ever and took greater trouble to pretend to hold up the train, which wasn’t there at all. THE END.”

Here we are in 2025, living in an era of remarkable scientific discovery. We are witnessing the preclinical development and subsequent clinical evaluation of
an ever-expanding array of novel antineoplastic strategies, seeing newly approved drugs or added clinical indications, and observing many advanced cancers being converted from illnesses with predicted short survivals (< 1-2 years) to more chronic disease processes with patients reasonably likely to live for several, if not many, years following diagnosis.

All good. Objective progress abounds. One might suggest only a true curmudgeon would even consider raising a serious complaint about the positive effect of measurable clinical outcomes being observed in well-designed trials in multiple cancer types.

But wait, the child asks, can someone provide a rational explanation for how the existing multiple uncoordinated, highly complex financial payment models in the US are supposed to work to optimize the welfare of patients with cancer at diagnosis during and following the treatment experience; enhance reasonable/nonwasteful clinical productivity while preventing physician burn- out; support innovation; develop and regularly update effective, low-cost decision-support tools; examine and potentially subsequently thoughtfully implement cost-effective therapeutic strategies; educate the next generation of clinicians; and also faithfully permit reasonable indi- vidual patient choice regarding the therapeutic journey?

Of course, as any objective external observer and likely the large majority of current participants (patients and their families, providers, health care administrators, regulators, payers, pharmaceutical companies, etc) involved in the process of the delivery of cancer care will appreciate, answers to the child’s questions are certain to be most unsatisfactory. Yet, as the Emperor declared, “the system is what we have, and the procession must go on.”

Speaking directly to the cancer care question, the US patent system, the employer-based insurance model, federal government payment strategy, individual state-based insurance regulations, and many other cancer care components were designed when cancer management was strikingly different from today.

For example, not that long ago, when cancers were either cured following surgery (possibly with added “adjuvant” local radiation therapy) or if the disease was advanced at diagnosis or later recurred following initial treatment, anticipated survival was quite short. Patented antineoplastic drug therapy might have been considered relatively expensive, but even the most expensive agents (consider the $1000-per-dose drug paclitaxel) were generally administered for a maximum of 4 to 6 cycles. This was due to both observed toxicity and likely relatively quick disease progression in most clinical settings.

Further, for most solid tumor types, there were few available, even marginally clinically effective second-line drugs. If they existed, disease progression was observed even faster than following the primary treatment program. 

Fast-forward to today: It is not uncommon for novel patented antineoplastic agents to cost more than $20,000 per course, with combination regimens and multiple supportive care medications included in the treatment cocktail. And of critical relevance to the issue of cost, with improved efficacy and decreased toxicity (both very good outcomes), treatment may reasonably and appropriately be continued for prolonged periods (“maintenance”), not infrequently exceeding 1 to 2 years.

Consider the following quite sobering facts: In 2023, total health care spending in the US was estimated to be $4.9 trillion. The rate of growth over the year (7.5%) had substantially accelerated compared with the preceding 2 years (4.2% and 4.6% in 2021 and 2022, respectively).

Viewed in an even more direct manner, this spending translates to $14,570 per person in the US. Multiple factors are responsible for this rate of increase, including the aging population with well-recognized greater medical care needs for older adults, rising expenditures for health care personel (impacted by labor shortages and high turnover), and the cost of drugs, including novel products taken chronically. These staggering increases in health care expenses and insurance premiums surely affect multiple aspects of society, including, as noted in a recent lay article, workers’ pay.

Of course, the provision of cancer care is at the forefront of the larger sobering issues facing health care systems and society. Multiple publications in the oncology and general medical literature have documented the financial impact associated with disease management, including worrying delays in seeking treatment with negative effect on clinical outcomes,

 and the widespread recognition of the role of financial hardship on the risk to a patient’s emotional wellbeing.

Although there are surely no simple solutions to the issues briefly highlighted above, is it finally time to fully appreciate their magnitude and begin to strategize how we might deal with the fiscal reality of “The Emperor’s New Clothes” in cancer management?

Hopefully, such efforts will rather quickly extend beyond existing academic energies focused on describing various forms of “financial toxicity,” as disturbing as the situations have clearly been shown to be, and actively move to explore (even if only as limited “pilots”) specific approaches developed to favorably influence the current trajectory. For example, thoughtful suggestions for impacting escalating drug costs and revamping the clinical trials process have recently been reported.5-7

A daunting task? Surely. But in situations like this, it is perhaps appropriate to note the oft-quoted words of Margaret Mead: “Never doubt that a small group of thoughtful, committed citizens can change the world. Indeed, it’s the only thing that ever has.” 

The current state of cancer care financing in the US is likened to "The Emperor's New Clothes," highlighting the disconnect between scientific advancements and outdated financial models. Despite significant progress in cancer treatment, the financial systems remain complex and uncoordinated, failing to optimize patient welfare, support innovation, or manage costs effectively. The rising costs of novel therapies and healthcare spending exacerbate financial toxicity, impacting patients' emotional well-being and access to care. Addressing these challenges requires innovative strategies and collaborative efforts to reshape the fiscal landscape of cancer management.

Maurie Markman, MD, discusses the complexities of cancer care financing in the US, highlighting the need for innovative solutions amidst rising costs.

Vol. 26 No. 5 | Oncology Live®

Researchers Address the Barriers to Remote Breast Cancer Symptom Monitoring in the US

The Move From Blood to Solid: Open Opportunities for CAR T-Cell Therapy in Solid Tumors

Combinations Targeting PI3K/AKT/mTOR and MAPK/ERK Pathways Are Under Study in Endometrial Cancer

ctDNA Aids in Elucidating the Role of Select Therapies for CRC

Combination Regimens Offer Options in Frontline RCC as Novel Agents Advance Through Pipeline

On the Unreality of Cancer Care Finances in the US: An Example of the Emperor's New Clothes Syndrome?