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With research institutions facing widespread layoffs and hiring freezes following deep cuts to federal funding for health agencies such as the National Institutes of Health (NIH) and National Cancer Institute (NCI), concerns about the long-term consequences for oncology research programs and biomedical progress in the US are escalating. These changes are already being felt across academic centers, clinical trial infrastructure, and cancer research programs.

Since President Donald J. Trump was inaugurated in January 2025, the current administration has taken several steps to reduce workforce and budget allocations for the US Department of Health and Human Services (HHS) through executive orders and restructuring mandates.

 In February, the NIH announced a 15% cap on grants for indirect costs, such as infrastructure and maintenance, which replaces previously negotiated indirect cost rates ranging from 25% to 70% at many universities.

Estimates from the Senate Health, Education, Labor and Pensions Committee suggest that as much as $2.7 billion in research grants was cut from the NIH in the first 3 months of 2025, and findings from recent analyses have shown that NIH grant rejections have more than doubled, with more than 2500 applications denied to date.

 An additional report from the Association of American Medical Colleges stated that the NIH terminated 777 grants as of May 5, 2025, which accounts for more than $1.9 billion in medical research funding.

Sweeping workforce reductions have followed these budgetary decisions. On March 27, HHS Secretary Robert F. Kennedy Jr announced 10,000 termination notices, including 1000 at the NIH—20% of which were later identified as errors.

 Additional layoffs in May affected 250 NIH employees, including approximately 50 staff at the NCI.

Such layoffs coincided with the release of the administration’s fiscal year 2026 budget on May 2, which outlined a nearly 40% reduction to NIH funding and consolidated the agency’s 27 institutes into just 8, though the NCI reportedly will be left intact.

“Health care is extremely complex, and the impact is going to be very different based on the structure of a given health system. If there are major federal cuts or reductions in indirect funds or grants coming in, those can be felt beyond simply just the university and can then affect the health system itself,” Daniel Spratt, MD, chairman and professor of radiation oncology at University Hospitals Seidman Cancer Center and Case Western Reserve University in Cleveland, Ohio, said in an interview with 

. “However, if the health system is functionally more autonomous from the university, they could be shielded potentially to a greater degree.”

Despite assurances from federal officials that the cuts would not compromise operations at the HHS, some emerging reports suggest otherwise. Several scientists at the NCI campus in Bethesda, Maryland, have reported delays in procuring essential supplies due to staffing cuts and policy changes, while others report that the institute is cutting contracts to maintain biological research specimens, according to an article release by KKF Health News in early July.

 The article was informed by interviews with more than 20 current and former NCI employees, academic researchers, scientists, and patients, many of whom chose to remain anonymous. Experts anticipate that such disruptions could have broader ramifications across the cancer research ecosystem, though Spratt does not anticipate an immediate, direct reduction of the oncology workforce.

“I don’t foresee that the federal cuts will have a direct implication on being able to have enough oncologists,” Spratt said. “[They] may have other ramifications, particularly related to research, the types of research questions being asked, and the prioritization of projects. We might [also] see a shift in what kinds of studies get done, or even where they get done.”

However, Spratt revealed that some of his colleagues at the NIH have begun transitioning to industry roles due to the uncertainty. Although these individuals continue to contribute to research, the shift may alter the questions being asked and who benefits from the findings. “There’s anxiety because there’s uncertainty, it’s scary, especially for those with large research portfolios and ongoing research.”

Historically, the US has been a global leader in oncology research, supported by substantial federal investments in biomedical science. With this infrastructure now in flux, experts worry about a slow-down in progress across cancer biology, translational research, and therapeutic development, particularly given the escalating cost of conducting trials domestically.

“There is still funding occurring, but there may need to be some pivots. If we just say, hypothetically, there is a clear reduction in federal funding for cancer research, then there will need to be commensurate increases in foundation support, philanthropy, and industry partnerships,” Spratt said. “Clinical trials, for example, have become exceptionally expensive in the US. [However], these high costs are driven by the high regulations and standards put in place. We may need to be more creative about how we conduct [trials going forward], reducing regulatory burdens without compromising safety and finding more cost-effective solutions that allow limited dollars to go further.”

Equity-focused research is also at risk. Although some researchers have been able to pivot their focus from race-based investigations to deeper analyses of socioeconomic and environmental drivers of disparities, others have faced greater scrutiny and decreased support.

“There are researchers who were focused on race-based health disparities who are now having to pivot. Many are choosing to frame their research around social determinants of health more broadly—economic status, education, and access to care—rather than focusing solely on race,” Spratt said. “Some of those programs continue, but they’re under much more scrutiny. And in other cases, funding just disappeared.” Spratt emphasized the importance of continuing to include diversity, equity, and inclusion in cancer research, but acknowledged that approaches must be adapted to changing regulatory and funding conditions.

Experts advocate for a range of strategic solutions to mitigate the impact of these cuts. These include lowering the cost of research by reducing regulatory burdens without compromising safety, improving clinical trial efficiency, and reallocating funding toward projects with the highest potential patient impact. There is also a call for enhanced collaboration between academia, government, and industry to develop new funding pipelines.

“The system we have for biomedical research in the US has many strengths, but there are opportunities for improvement,” Spratt said. “[We] need to think carefully about how to ensure their programs remain viable. We can’t keep doing research just for the sake of it as there are career researchers whose work does not clearly translate to patient benefit. We must navigate the current climate by aiming for a more cost-effective, robust ability to perform research that helps people, not just to maintain funding or conduct research for its own sake.”

In the near term, experts such as Spratt are optimistic about the imminent stabilization of the federal funding landscape. Given the scale of proposed cuts, however, the research community must remain adaptable.

“We have had, for decades, clear-cut paths for academic researchers to obtain funding. This is an awakening moment,” Spratt emphasized. “Individuals must now think carefully about how to ensure the sustainability of their programs and whether their research is truly designed to translate from bench to bedside.”

He concluded, “If you’re pursuing high-impact science that is focused on benefiting patients, there are still many avenues for success. We have a brilliant scientific community in the US, and this community must keep moving forward with helping humankind as our north star.”

Trump’s 2025 executive orders. Holland & Knight LLP. Accessed June 30, 2025. https://www.hklaw.com/en/general-pages/trumps-2025-executive-orders-chart

Martin S, Merrill R, Bourque D, et al. NIH cuts research funding for indirect costs. Holland & Knight LLP. February 10, 2025. Accessed June 30, 2025. https://www.hklaw.com/en/insights/publications/2025/02/nih-cuts-research-funding-for-indirect-costs#:~:text=The%20indirect%20cost%20rate%20is,security%20and%20biosafety,%20and%20utilities.

Sanders releases report documenting Trump’s war on science. News release. US Senate Committee on Health, Education, Labor and Pensions. May 13, 2025. Accessed June 30, 2025. https://www.help.senate.gov/dem/newsroom/press/news-sanders-releases-report-documenting-trumps-war-on-science

Mallapaty S. Exclusive: NIH grant rejections have more than doubled amid Trump chaos. 

. Published online May 19, 2025. doi:10.1038/d41586-025-01539-5

Impact of NIH grant terminations. Association of American Medical Colleges. May 27, 2025. Accessed June 30, 2025. https://www.aamc.org/about-us/mission-areas/medical-research/publication/impact-nih-grant-terminations

Masson G. 250 more NIH workers laid off, including cuts at the National Cancer Institute. Fierce Biotech. May 6, 2025. Accessed June 30, 2025. https://www.fiercebiotech.com/biotech/250-more-nih-workers-laid-including-cuts-national-cancer-institute

The White House. Major discretionary funding changes. May 2, 2025. Accessed June 30, 2025. https://www.whitehouse.gov/wp-content/uploads/2025/05/Fiscal-Year-2026-Discretionary-Budget-Request.pdf

Choi J, O’Connel-Domenech A, Weixel N. White House asks for steep cuts to HHS budget. The Hill. June 2, 2025. Accessed June 30, 2025. https://thehill.com/newsletters/health-care/5329525-white-house-hhs-budget-nih/

Pradhan R, Allen A. World’s premier cancer institute faces crippling cuts and chaos. July 9, 2025. Accessed July 16, 2025. https://kffhealthnews.org/news/article/national-cancer-institute-nih-cuts-chaos-scientific-biomedical-research/

Articles

Federal funding cuts to health agencies like the NIH and NCI have led to significant layoffs and hiring freezes, raising concerns about the future of oncology research in the US. The current administration's budget reductions have resulted in a 40% cut to NIH funding and consolidation of its institutes. These changes have disrupted research programs, delayed procurement of essential supplies, and forced some researchers to transition to industry roles. Experts emphasize the need for strategic solutions, including reducing regulatory burdens and enhancing collaboration, to mitigate the impact of these cuts on cancer research.

Oncology Business Management 

Following cuts to federal funding for health agencies, concerns about the long-term consequences for research programs in the US are escalating.

Federal Funding Cuts Spark Concern Over Future of Cancer Research and Care in United States

Multiple myeloma treatment has undergone a dramatic transformation in recent years, ushering in a new era of therapeutic possibilities. With the emergence of advanced immunotherapies and targeted agents, we have entered a new therapeutic era—particularly for patients with relapsed/refractory disease. Outcomes are improving, deeper remissions are becoming more common, and there is increasing discussion around the possibility of functional cures for select patient populations. 

A Look at the Novel Therapeutic Landscape

CAR T-cell therapy has redefined the prognosis for many patients with heavily pretreated disease. Idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel; Carvykti) have demonstrated high response rates and durable remissions in patients with triple- or penta-refractory multiple myeloma. The FDA first approved ide-cel in March 2021 for the treatment of patients with relapsed/refractory multiple myeloma after 4 or more prior lines of therapy, which included an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody.

 In February 2022, the FDA approved cilta-cel for the treatment of patients with relapsed/refractory multiple myeloma following 4 or more lines of treatment, including an IMiD, a PI, and an anti-CD38 monoclonal antibody.

 Both CAR T-cell therapies were approved in April 2024, which reflected utilizing ide-cel and cilta-cel in earlier lines of therapy. Ide-cel was specifically approved for the treatment of patients with relapsed/refractory multiple myeloma following 2 or more prior lines of therapy, including an IMiD, a PI, and an anti-CD30 monoclonal antibody.

 In a similar trend, cilta-cel was approved for the treatment of patients with relapsed/refractory multiple myeloma who were previously treated with at least 1 line of therapy, including an IMiD, a PI, and those who were refractory to lenalidomide (Revlimid).

While logistical challenges— such as T-cell harvesting, manufacturing time, and insurance barriers— remain, the clinical impact of these therapies is undeniable. Toxicity, particularly cytokine release syndrome and neurotoxicity, requires vigilance and experienced management. 

Bispecific T-cell engagers represent a compelling alternative, offering off-the-shelf access compared with autologous CAR T cells. Agents such as teclistamab (targeting BCMA; Tecvayli), elranatamab (BCMA; Elrexfio), and talquetamab (GPRC5D; Talvey) are demonstrating strong efficacy, even in patients with refractory disease. These therapies are also being tested in earlier lines, with the potential to replace or augment current standard regimens. 

Belantamab mafodotin (Blenrep), an anti-BCMA antibody-drug conjugate, initially offered a novel option for relapsed/refractory multiple myeloma when it was FDA-approved in August 2020, but was withdrawn from the US market because the phase 3 DREAMM-3 trial (NCT04162210) did not meet its primary end point of progression-free survival.

 However, clinical refinement in dosing and ocular toxicity management may support its return in a revised form. Its unique mechanism could reestablish its place as part of a multimodal strategy. 

Selinexor (Xpovio), an oral selective inhibitor of nuclear export (XPO1), has been incorporated into treatment regimens for relapsed/refractory disease, typically in combination with PIs or IMiDs. Although it is not curative, its inclusion has broadened the armamentarium and provided options for patients whose disease is more difficult to treat. 

These advancements herald a new era in multiple myeloma treatment, characterized by deeper and more durable remissions. Emerging data indicate higher rates of minimal residual disease negativity, particularly with CAR T-cell therapies and bispecific antibodies. Although still rare, the possibility of functional cures is becoming a reality, with some patients experiencing long-term, treatment-free remission after CAR T-cell therapy. The expanding therapeutic arsenal allows for increasingly personalized treatment pathways, tailoring therapies based on prior treatment exposures, individual mutational profiles, and comorbidities. Furthermore, ongoing clinical trials are evaluating the use of novel therapies in earlier treatment lines, potentially reshaping the role of autologous stem cell transplantation (ASCT) and solidifying this new era of improved outcomes in multiple myeloma. 

The pace of discovery in multiple myeloma is accelerating. In the near term, several shifts are anticipated that could further improve patient outcomes, including the following: 

Earlier use of immunotherapies: Clinical trials are exploring CAR T-cell and bispecific therapies earlier in the disease course. If data continue to show high efficacy and manageable toxicity, we may see a paradigm shift toward earlier immunebased interventions. 

Post-transplant immune modulation: Leveraging bispecific antibodies and other immune-targeted therapies in the post-ASCT setting could enhance consolidation and delay relapse. 

Next-generation agents: Improved versions of CAR T cells, including dual-targeting constructs and allogeneic platforms, are on the horizon. Likewise, novel bispecific antibodies with extended half-lives and improved safety profiles are in development. 

Biomarker-guided precision medicine: Genomic and molecular profiling is beginning to guide treatment decisions. As more validated biomarkers emerge, expect a shift toward stratified therapy, especially for high-risk cytogenetics or extramedullary disease. 

Optimized combination regimens: Ongoing studies are refining how novel agents can be best combined with existing standards—such as IMiDs, PIs, and monoclonal antibodies—to increase response depth and duration. 

Enhanced quality of life: A growing focus is being placed on treatment tolerability, minimizing steroid burden, and maximizing time off therapy. Patient-reported outcomes will continue to influence drug development and regulatory decisions. 

Outpatient delivery of complex therapies: Many centers are transitioning select patients to outpatient administration of CAR T-cell and bispecific antibody therapies, improving convenience and resource utilization. 

We are witnessing a renaissance in multiple myeloma therapy, marked by unprecedented options and optimism. While a cure remains elusive for most, the trajectory is unmistakably upward, with longer remissions, fewer complications, and a more nuanced approach to each patient’s disease. 

As this field continues to evolve, staying abreast of trial data, novel approvals, and real-world outcomes will be critical. The future of multiple myeloma management lies in balancing efficacy with safety, access with personalization, and innovation with equity. 

FDA approves idecabtagene vicleucel for multiple myeloma. FDA. March 29, 2021. Accessed June 26, 2025. https://www.fda.gov/drugs/ resources-information-approved-drugs/fda-approves-idecabtagenevicleucel- multiple-myeloma

FDA approves ciltacabtagene autoleucel for relapsed or refractory multiple myeloma. FDA. Updated March 7, 2022. Accessed June 26, 2025. https:// www.fda.gov/drugs/resources-information-approved-drugs/fda-approvesciltacabtagene- autoleucel-relapsed-or-refractory-multiple-myeloma U.S. FDA approves Bristol Myers Squibb and 2seventy bio’s Abecma for triple-class exposed relapsed or refractory multiple myeloma after two prior lines of therapy. News release. Bristol Myers Squibb. April 5, 2024. Accessed June 26, 2025. https://news.bms.com/news/details/2024/ U.S.-FDA-Approves-Bristol-Myers-Squibb-and-2seventy-bios-Abecma-for- Triple-Class-Exposed-Relapsed-or-Refractory-Multiple-Myeloma-After-Two- Prior-Lines-of-Therapy/default.aspx

Carvykti is the first and only BCMA-targeted treatment approved by the U.S. FDA for patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. News release. Johnson & Johnson. April 6, 2024. Accessed June 26, 2025. https://www.jnj.com/ media-center/press-releases/carvykti-is-the-first-and-only-bcma-targetedtreatment- approved-by-the-u-s-fda-for-patients-with-relapsed-or-refractorymultiple- myeloma-who-have-received-at-least-one-prior-line-of-therapy

FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma. FDA. Updated March 7, 2024. Accessed June 26, 2025. https://www.fda.gov/drugs/resources-information-approveddrugs/ fda-granted-accelerated-approval-belantamab-mafodotinblmf- multiple-myeloma

Recent advancements in multiple myeloma treatment have significantly improved patient outcomes, particularly for relapsed/refractory cases. CAR T-cell therapies, such as ide-cel and cilta-cel, have shown high response rates and durable remissions. Bispecific antibodies and antibody-drug conjugates offer promising alternatives, while XPO1 inhibitors expand treatment options. The potential for functional cures is increasing, with personalized treatment pathways becoming more prevalent. Ongoing research aims to optimize combination regimens, enhance quality of life, and explore earlier use of immunotherapies, potentially reshaping the role of autologous stem cell transplantation.

The emergence of immunotherapies and targeted agents has ushered in a new era in relapsed/refractory multiple myeloma.

A New Era In Multiple Myeloma Treatment: Advances and Future Directions

Although conventional CTLA-4 inhibitors such as ipilimumab (Yervoy) and tremelimumab-actl (Imjudo) helped to spark the immunotherapy revolution in cancer care, these agents have generally been most effective in patients with immune-inflamed disease.

 To extend the benefits of this class of therapies to patients with poorly immunogenic solid tumors, such as hepatocellular carcinoma (HCC), colorectal cancer (CRC), and pancreatic cancer, investigators are developing fragment crystallizable (Fc)–enhanced CTLA-4 inhibitors, including botensilimab (AGEN1181) and vilastobart (XTX101).

Fc-enhanced CTLA-4 inhibitors are designed to have affinity for the Fcγ receptor; coengagement with this receptor is believed to play a key role in the activity of CTLA-4 inhibitors.

 These agents leverage Fcγ receptor–dependent mechanisms to increase T-cell responsiveness, decrease intratumoral regulatory T cells (Tregs), and enhance antigen-presenting cell activation.

“Botensilimab is a second-generation CTLA-4 inhibitor,” Bruno B. Bockorny, MD, explained in an interview with 

. “Aside from binding to CTLA-4, it has point mutations in the Fc region of the antibody that [enable] increased binding to the activating Fcγ receptor on both antigen-presenting cells and natural killer cells. This mutation [confers] several unique mechanisms relative to first-generation CTLA-4 inhibitors, [such as] increased priming and memory formation of T cells, [which] increases activation of antigen-presenting cells. [This mechanism] also leads to a further decrease in immunosuppressive Tregs and a decrease in complement and mediated toxicities.”

Bockorny is an assistant professor of medicine at Harvard Medical School and a medical oncologist at Beth Israel Deaconess Medical Center in Boston, Massachusetts.

Fc-Enhanced CTLA-4 Inhibitors Display Efficacy in HCC and CRC

Botensilimab is being evaluated as monotherapy and in combination with the anti–PD-1 antibody balstilimab (AGEN2034) in patients with pretreated solid tumors, including HCC, in the phase 1 C-800-01 study (NCT03860272).

 The HCC cohort of C-800-01 included patients who experienced disease progression on or after treatment with a previous immunotherapy. Patients had received a median of 2 prior lines of therapy (range, 1-7), and 26% had received at least 3 previous lines of treatment.

Findings from C-800-01 presented during the 2025 American Association for Cancer Research Annual Meeting revealed that efficacy-evaluable patients in the HCC cohort who received the combination (n = 18) achieved an overall response rate (ORR) of 17% (95% CI, 4%-41%), which comprised partial responses exclusively. The disease control and clinical benefit rates were 72% (95% CI, 47%-90%) and 50% (95% CI, 26%-74%), respectively. The median duration of response, progression-free survival, and overall survival were not reached (NR; 95% CI, 9.8-NR), 4.4 months (95% CI, 1.4-6.9), and 12.3 months (95% CI, 8.4-21.4), respectively.

No treatment-related deaths were reported in the safety population (n = 19). Any-grade immune-mediated treatment-related adverse effects (TRAEs) occurred at a rate of 68% and included diarrhea/colitis (37%), hepatitis (21%), and adverse skin reactions (21%). Grade 3 immune-mediated TRAEs occurred in 37% of patients, with the most common being diarrhea/colitis (16%) and hepatitis (16%).

Botensilimab plus balstilimab is also being tested as neoadjuvant therapy in patients with resectable mismatch repair–proficient and –deficient CRC in the phase 2 NEST-1 trial (NCT05571293).

 The trial’s protocol included patients who received one 75-mg dose of botensilimab plus two 240-mg doses of balstilimab 2 weeks apart (NEST-1) or botensilimab at the same dose as NEST-1 plus up to 4 doses of balstilimab 2 weeks apart (NEST-2).

Data from NEST presented during the 2025 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) showed that patients with microsatellite stable (MSS) CRC treated with the NEST-1 regimen (n = 7) achieved a pathologic complete response (pCR) rate of 14% (95% CI, 0.4%-58%). The major pathologic response (MPR) rate was 29% (95% CI, 4%-71%). The pCR and MPR rates were 40% (95% CI, 16%-68%) and 47% (95% CI, 21%-73%), respectively, among patients with MSS disease treated with the NEST-2 regimen (n = 15). These respective rates were 75% (95% CI, 19%-99%) and 100% (95% CI, 40%-100%) in patients with microsatellite instability–high tumors who received either regimen (n = 4).

Another Fc-enhanced CTLA-4 inhibitor, vilastobart, is being examined in patients with advanced solid tumors, including metastatic MSS CRC, in a phase 1/2 trial (NCT04896697).

 Vilastobart is a tumor-activated agent with high-affinity binding and significantly higher potency than ipilimumab in a preclinical study. The drug is designed to focus its activity on tumor cells and minimize systemic exposure to reduce potential AEs.

Data from the phase 2 portion of the first-in-human study presented during the 2025 ASCO Annual Meeting showed that patients with MSS CRC without liver metastases (n = 27) who received vilastobart in combination with atezolizumab (Tecentriq) achieved an ORR of 26% per RECIST 1.1 criteria. Six of the patients who achieved a response remained on therapy at the data cutoff. Notably, the overall cohort (n = 44), which included patients with and without liver metastases, was heavily pretreated, having received a median of 4 prior lines of therapy (range, 1-8).

No grade 5 TRAEs were reported in terms of safety. The most common any-grade TRAEs included fatigue (30%), infusion-related reactions (23%), and diarrhea/colitis (20%). Two patients discontinued treatment due to TRAEs.

The study authors concluded that these findings support the further development of vilastobart-based combinations in patients with MSS CRC and other cold tumors.

Botensilimab Set for Evaluation as Combination Component in Pancreatic Cancer

Beyond the HCC and CRC spaces, botensilimab plus balstilimab is now being added to combination chemotherapy for the treatment of patients with previously untreated metastatic pancreatic cancer in an ongoing phase 1 trial (NCT06076837).

 In addition to the doublet, patients will also receive triplet chemotherapy with nab-paclitaxel (Abraxane), gemcitabine, and cisplatin. Then, in part 2, patients will receive the same regimen plus chloroquine phosphate (Aralen) and celecoxib (Celebrex), if 1 or fewer dose-limiting toxicities are reported in the 6 patients treated in part 1.

“In trying to understand how to improve ther- apies for patients with pancreatic cancer, we’ve looked at immunotherapy and the autophagy pathway,” Erkut H. Borazanci, MD, medical director of the Oncology Research Division at HonorHealth Research Institute in Scottsdale, Arizona, said in an interview with 

. “The idea is to do what we can to stress the cancer cells. This concept [involves] the unfolded protein response, where you’re stressing these cancer cells and pushing them into apoptosis. The base of [the regimen] is chemotherapy, [then] we’re adding the autophagy agent chloroquine, combining that with botensilimab and balstilimab, and adding the COX-2 inhibitor celecoxib in a 7-drug combination.”

To be eligible for enrollment, patients with previously untreated, histologically confirmed metastatic pancreatic ductal adenocarcinoma must be at least 18 years old and have an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, measurable disease per RECIST 1.1 criteria, and no history of central nervous system metastasis. The study’s primary objectives are to determine the maximum tolerated dose of botensilimab and evaluate the full combination’s safety and tolerability.

Additionally, in an ongoing phase 2 study (NCT05632328), botensilimab is being evaluated in combination with the TGFβ and CD73-adenosine inhibitor dalutrafusp alfa (AGEN1423) in patients with advanced pancreatic cancer.

 Investigators have hypothesized that the combination can rescue T-cell functional activity, leading to responses in these patients.

The study is enrolling adult patients with metastatic pancreatic cancer who experienced radiographic disease progression after previous systemic therapy, have measurable disease per RECIST 1.1 criteria, and have received no prior anti–CTLA-4 therapy. The primary end point is ORR per RECIST 1.1 criteria.

“We’re very excited that the first cohort [of patients is being treated] with botensilimab and dalutrafusp alfa,” Bockorny said. “[Study] enrollment has been completed, and so far we have not seen any new safety signals. We are waiting for the data to mature so we can [better] understand the efficacy. I believe later [in 2025], we are going to have a good readout for the study and decide whether or not to move forward with cohort 2, where we will combine botensilimab and [dalutrafusp alfa] with standard gemcitabine and nab-paclitaxel.”

Chand D, Savitsky DA, Krishnan S, et al. Botensilimab, an Fc-enhanced anti-CTLA-4 antibody, is effective against tumors poorly responsive to conventional immunotherapy. 

. 2024;14(12):2407-2429. doi:10.1158/2159-8290.CD-24-0190

El-Khoueiry AB, Abou-Alfa GK, Wilky BA, et al. Results from a phase 1 study of botensilimab and balstilimab in treatment refractory hepatocellular carcinoma. 

. 2025;85(8 suppl 2):LB365. doi:10.1158/1538-7445.AM2025-LB365

Hissong E, Jafari MD, Khan S, et al. Neoadjuvant botensilimab (BOT) plus balstilimab (BAL) in resectable mismatch repair proficient (pMMR) and deficient (dMMR) colorectal cancer (CRC): NEST clinical trial update. 

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Fakih M, DeVito NC, Parikh AR, et al. Vilastobart (XTX101), a tumor-activated, Fc-enhanced anti–CTLA-4 monoclonal antibody, in combination with atezolizumab in patients with MSS CRC. 

. 2025;43(suppl 16):3553. doi:10.1200/JCO.2025.43.16_suppl.3553

Borazanci EH, Jameson GS, Carter B, et al. An open-label, phase 1 trial with expansion cohort of botensilimab (AGEN1181) + balstilimab (AGEN2034) + nab-paclitaxel + gemcitabine + cisplatin + chloroquine + celecoxib in adult patients with previously untreated metastatic pancreatic cancer.

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Bockorny B, Berg J, Bullock AJ, et al. A phase 2 study of botensilimab and AGEN1423, an anti-CD73-TGFβ-trap bifunctional antibody, with or without chemotherapy in subjects with advanced pancreatic cancer.

. 2025;43(suppl 16):TPS4231. doi:10.1200/JCO.2025.43.16_suppl.TPS4231

Fc-enhanced CTLA-4 inhibitors, such as botensilimab and vilastobart, are being developed to improve immunotherapy outcomes in poorly immunogenic solid tumors like HCC, CRC, and pancreatic cancer. These agents enhance T-cell responsiveness and reduce immunosuppressive Tregs. Botensilimab, in combination with balstilimab, has shown promising results in HCC and CRC, with ongoing trials in pancreatic cancer. Vilastobart, combined with atezolizumab, demonstrated efficacy in MSS CRC. These findings support further development of Fc-enhanced CTLA-4 inhibitors in various cancer types, aiming to improve patient outcomes.

Pathways

To extend the benefits of CTLA-4 inhibitors to poorly immunogenic tumors such as HCC and CRC, investigators are developing Fc-enhanced CTLA-4 inhibitors.

Fc-Enhanced Agents May Expand Anti–CTLA-4 Approaches in GI Cancers

Methods to accurately predict which patients are the most likely to benefit from therapy can be elusive, according to Joyce O'Shaughnessy, MD. However, updated findings have indicated that the MammaPrint and BluePrint genomic tests could offer a predictive testing approach to elucidate which patients with hormone receptor (HR)–positive, HER2-negative early-stage breast cancer should receive adjuvant and/or neoadjuvant chemotherapy.

MammaPrint is a 70-gene assay that analyzes the most important genes associated with breast cancer recurrence.

 The MammaPrint index classifies patients as being at high risk 2 (H2; range, –1.000 to –0.570), high risk 1 (H1; range, –0.569 to 0.000), low risk (range, 0.001-0.355), or ultralow risk (range, 0.356-1.000) for disease recurrence.1 BluePrint is an 80-gene test that classifies patients into luminal (further stratified using MammaPrint into luminal A-type [low risk] and luminal B-type [high risk]), HER2, or basal subtypes, providing insights into their long-term prognosis and potential response to systemic treatment.

“In patients with HR-positive, HER2-negative early breast cancer, the first question is, ‘Who needs chemotherapy at all?’” O’Shaughnessy said in an interview with OncologyLive. “[Most] patients will receive endocrine therapy, and if they have high enough risk disease, they will receive a CDK4/6 inhibitor. Patients with a low 21-gene recurrence score don’t benefit from chemotherapy. We know that the MammaPrint [test] is prognostic due to data from the [phase 3] MINDACT trial [NCT00433589], but we did not [previously] have data [that] indicated that a high-risk MammaPrint score predicts benefit from chemotherapy or that a low-risk score predicts a lack of benefit.”

O’Shaughnessy is the Celebrating Women Chair in Breast Cancer Research at Baylor University Medical Center and the director of the Breast Cancer Research Program at Texas Oncology, US Oncology, in Dallas.

MammaPrint and BluePrint Show Predictive Value

To further understand the predictive value of the tests on patient outcomes, investigators initiated the prospective, observational FLEX registry study (NCT03053193).

 FLEX enrolled adult patients with stage I to III breast cancer who were eligible to receive chemotherapy and endocrine therapy and MammaPrint, with or without BluePrint testing, in any clinical setting. The study excluded patients with metastatic, recurrent, or stage 0 disease.

During the 2024 San Antonio Breast Cancer Symposium (SABCS), O’Shaughnessy presented data from an analysis of FLEX that demonstrated that MammaPrint and BluePrint were able to predict sensitivity to neoadjuvant chemotherapy in patients with HR-positive, HER2-negative early breast cancer. 

Patients with H2 luminal and basal disease (n = 159) achieved a pathological response rate of 32.7%, with a pathological complete response (pCR) rate of 28.3%. Those with H2 luminal B-type (n = 70) or H2 basal (n = 83) disease experienced pathological response rates of 21.4% and 43.4%, respectively, with respective pCR rates of 15.7% and 39.8%. Comparatively, patients with low-risk luminal A-type disease (n = 44) experienced a pathological response rate of 4.5%, and those with H1 luminal B-type disease (n = 242) experienced a pathological response rate of 9.5%, with a pCR rate of 7.4%. 

Data from a multivariate analysis also revealed that a MammaPrint H2 classification was significantly associated with a pathological response compared with H1 status (OR, 3.33; 95% CI, 1.51-7.61; 

Additional data from FLEX also presented during SABCS showed that patients with a higher-risk MammaPrint score who received adjuvant chemotherapy plus endocrine therapy (n = 501) had a significantly lower risk of 5-year distant recurrence or breast cancer–specific death (DRFI) compared with those who received endocrine therapy alone (n = 501). Patients with an ultralow MammaPrint score who received endocrine therapy experienced a 1.0% (95% CI, 0.6%-2.2%) average 5-year DRFI risk vs 0.4% (95% CI, 0.1%-1.0%) among those who received chemotherapy plus endocrine therapy. Among patients with a low score, these respective rates were 3.2% (95% CI, 2.2%-4.5%) and 1.5% (95% CI, 1.0%-2.1%).

Notably, patients in the H1 group who received endocrine therapy alone experienced an average 5-year DRFI risk of 10.0% (95% CI, 5.6%-14.6%) compared with 4.4% (95% CI, 2.6%-6.4%) among patients who received endocrine therapy plus chemotherapy, for a risk difference of 5.6% (95% CI, 3.0%-8.2%). In the H2 risk group, these rates were 19.1% (95% CI, 14.8%-24.8%) vs 8.2% (95% CI, 6.5%-10.6%), respectively, representing a risk difference of 10.9% (95% CI, 8.3%-14.2%).

“These are the first data using MammaPrint showing that the higher the risk [score], the greater the benefit from chemotherapy,” O’Shaughnessy noted. “We’ve been giving chemotherapy to those women anyway because we know they have a poor prognosis, but this is the first time we’ve seen level 1, prospective, predictive data. The caveat here is that this is not a randomized trial. This [study] has a large database of real-world evidence, but the deci- sion to give chemotherapy or not is made by the physician and patient.”

Findings from FLEX have also shown the capability of MammaPrint and BluePrint to help inform the need for the addition of an anthracycline to chemotherapy. 

During the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, O’Shaughnessy presented data from FLEX that demonstrated that patients with H1 luminal disease who received an anthracycline plus a taxane (n = 184) achieved a 3-year relapse-free survival (RFS) rate of 95.3% (95% CI, 91.8%-98.8%) compared with 97.1% (95%, 95.1%-99.2%) among those who received a taxane plus cyclophosphamide (n = 346). However, patients with luminal H2 tumors who received an anthracycline plus a taxane (n = 44) experienced a 3-year RFS rate of 97.7% (95% CI, 93.4%-100%) vs 86.4% (95% CI, 74.2%-100.0%) among those who received a taxane plus cyclophosphamide (n = 40).

“Both of these tests are endorsed by National Comprehensive Cancer Network and ASCO guidelines, so I don’t believe there are any barriers [to access],” O’Shaughnessy said. “In FLEX, MammaPrint and BluePrint are also being evaluated in [patients with] HER2-positive and triple-negative disease. There could potentially be some limitations on reimbursement there because it is a research trial. However, if we look at [data from] MINDACT, there were patients with triple-negative breast cancer who didn’t benefit from chemotherapy if they had a low-risk MammaPrint score. If they had a high-risk MammaPrint score, they had a worse prognosis and did benefit from chemotherapy.”

She added, “In general, in the HR-positive, HER2-negative context, there are not any barriers to ordering [these tests], getting the results in a timely fashion, or to reimbursement.”

Breast Cancer Experts Gather at SOBO to Discuss the Latest Data

School of Breast Oncology® (SOBO), hosted by Physicians’ Education Resource®, LLC (PER®), expert investigators in the field of breast cancer will gather to further discuss how molecular and genomic testing can be used to optimally select treatment approaches for individual patients. O’Shaughnessy will chair the event, which will also feature sessions on present and emerging imaging modalities, best practices for the locoregional treatment of patients with breast cancer, and the latest clinical trial data that could shape future therapeutic approaches. The program will be held November 6-8, 2025, in Atlanta, Georgia.

“SOBO will be a 3-day deep dive [that will cover] new data based around case discussions [that aim to determine] how we apply these new data to practice,” O’Shaughnessy said. “I always thoroughly enjoy the data presentations but am also [looking forward to] the spirited interactions that occur during a moderated case and panel discussion between the reconstructive surgeons, the plastic surgeons, and the radiation oncologists.”

Updated findings suggest that MammaPrint and BluePrint genomic tests can predict which patients with HR-positive, HER2-negative early-stage breast cancer may benefit from chemotherapy. MammaPrint, a 70-gene assay, and BluePrint, an 80-gene test, provide insights into recurrence risk and treatment response. The FLEX registry study demonstrated their predictive value, showing significant associations between MammaPrint scores and chemotherapy benefits. Data from the study also highlighted the potential role of these tests in guiding anthracycline use. These tests are endorsed by major guidelines and are being evaluated for broader applications.

Joyce O'Shaughnessy, MD, discusses the utility of genomic testing in HR+, HER2– early breast cancer.

Genomic Tests for HR+/HER2– Early Breast Cancer Show Utility Beyond Predicting Prognosis

Five experts gathered for an OncLive Peer Exchange to discuss notable changes in the small cell lung cancer treatment paradigm.

The small cell lung cancer (SCLC) treatment paradigm is experiencing unprecedented progress as emerging data about immunotherapies, maintenance strategies, and antibody-drug conjugates (ADCs) fuel optimism in the field and reinforce the vital role of multidisciplinary collaboration.

“At [the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting], we had 2 practice-changing studies,” Anne Chiang, MD, PhD, said during a recent 

 Peer Exchange. “There [has been] more progress within the past year than there has been in the past 30 to 40 years. This is an exciting time for our patients, for our research teams, and for clinical care.”

During the panel discussion, SCLC experts discussed updates from ASCO 2025. They highlighted current treatment standards for limited-stage SCLC (LS-SCLC) and extensive-stage SCLC (ES-SCLC), practice-changing data in the ES-SCLC first-line maintenance setting, and where the future is headed regarding postprogression management strategies in the second-line setting and beyond. Multidisciplinary collaboration considerations were featured heavily in the discussion, as the panelists emphasized that the growing complexity of SCLC treatment developments necessitates frequent communication with colleagues including radiation oncologists, palliative care teams, pulmonologists, nutritionists, physical therapists, and social workers to ensure the delivery of comprehensive patient care.

Postchemoradiotherapy Duvalumab Retains Its Role in LS-SCLC

In December 2024, the FDA approved durvalumab (Imfinzi) for the treatment of adult patients with LS-SCLC whose disease has not progressed after concurrent platinum-based chemotherapy and radiotherapy.

 This regulatory decision was supported by data from the phase 3 ADRIATIC trial (NCT03703297), in which patients who received durvalumab (n = 264) experienced a statistically significant overall survival (OS) benefit compared with those who received placebo (n = 266), with a median OS of 55.9 months (95% CI, 37.3-not estimable) vs 33.4 months (95% CI, 25.5-39.9), respectively (HR, 0.73; 95% CI, 0.57-0.93; 

 Patients in the durvalumab arm also achieved a statistically significant progression-free survival (PFS) improvement vs those in the placebo arm, with a median PFS of 16.6 months (95% CI, 10.2-28.2) vs 9.2 months (95% CI, 7.4-12.9), respectively (HR, 0.76; 95% CI, 0.61-0.95; 

Although ADRIATIC established durvalumab as a postchemoradiotherapy standard of care (SOC) for patients with LS-SCLC, findings from the phase 2 trial ACHILES (NCT03540420) presented at ASCO 2025 did not show a similar benefit with the use of atezolizumab (Tecentriq) in this setting.

 The median OS from randomization was 43.3 months (95% CI, 25.1-51.2) among patients who received atezolizumab (n = 85) vs 38.8 months (95% CI, 25.8-57.6) among those who underwent observation (n = 85; HR, 1.14; 95% CI, 0.76-1.71; 

 = .53). The median PFS in these respective arms was 21.1 months (95% CI, 9.5-43.4) vs 15.9 months (95% CI, 10.6-24.0; HR, 0.89; 95% CI, 0.61-1.30; 

 = .55). Based on these data, the panelists noted that durvalumab remains the SOC for this population.

“One thing I want to emphasize here is the need for multidisciplinary care for patients with SCLC,” Christine Lovly, MD, PhD, FASCO, noted regarding the use of radiotherapy in the LS-SCLC population. “Conversations about once-a-day [radiation] vs twice-a-day radiation vs prophylactic cranial irradiation are conversations we’re having with the patients, with medical oncology, [and] with radiation oncology. [I] want to underscore the importance of that close communication with the radiation oncologists.”

Atezolizumab and Durvalumab Continue Their Footholds in First-Line ES-SCLC

In March 2019, the FDA granted approval to the PD-L1 inhibitor atezolizumab plus carboplatin and etoposide for the first-line treatment of patients with ES-SCLC based on data from the phase 3 IMpower133 trial (NCT02763579).

 The median OS was 12.3 months in the atezolizumab arm vs 10.3 months in the chemotherapy-alone arm (HR, 0.70; 95% CI, 0.54-0.91; 

The first-line treatment paradigm for this population was further expanded in March 2020 with the FDA approval of durvalumab in combination with etoposide and either carboplatin or cisplatin, which was backed by findings from the phase 3 CASPIAN trial (NCT03043872).

In this trial, the median OS was 13.0 months (95% CI, 11.5-14.8) with durvalumab plus chemotherapy vs 10.3 months (95% CI, 9.3-11.2) with chemotherapy alone (HR, 0.73; 95% CI, 0.59-0.91; 

Based on these regulatory decisions, atezolizumab and durvalumab are established SOC for patients with previously untreated ES-SCLC.

“I think of them in the clinic as interchangeable, but [I acknowledge] that there are some data, if we had to pick, [indicating greater] efficacy [with] durvalumab,” Catherine Meador, MD, PhD, said. “We’re going to see more of these exciting, novel agents in the later line being moved to first-line testing in combination with PD-L1 [inhibitors]. Ultimately, that will start to affect our first-line choice of PD-L1 inhibitor.”

Shifting First-Line Maintenance Strategies Raise Questions in ES-SCLC

Data from the phase 3 IMforte trial (NCT05091567) presented at ASCO 2025 showed that in patients with ES-SCLC whose disease did not progress after first-line induction therapy with carboplatin, etoposide, and atezolizumab, first-line maintenance therapy with the combination of lurbinectedin (Zepzelca) and atezolizumab significantly improved both PFS and OS compared with atezolizumab monotherapy (Table 1).

 The median PFS was 5.4 months (95% CI, 4.2-5.8) with lurbinectedin plus atezolizumab (n = 242) vs 2.1 months (95% CI, 1.6-2.7) with atezolizumab alone (n = 241; stratified HR, 0.54; 95% CI, 0.43-0.67; 2-sided 

 < .0001). The median OS in these respective arms was 13.2 months (95% CI, 11.9-16.4) compared with 10.6 months (95% CI, 9.5-12.2; stratified HR, 0.73; 95% CI, 0.57-0.95; 2-sided

“This immediately was practice changing,” Misty Shields, MD, PhD, emphasized. “This is an area of vulnerability for patients who have extensive- stage [disease], have had a brisk or meaningful response after induction chemoimmunotherapy, and then switched to immunotherapy and relapsed. [Lurbinectedin plus atezolizumab] is a helpful option to add for patients with extensive-stage [disease] in the maintenance setting to help prevent that high risk of relapse we see with immunotherapy alone.”

Cytotoxic Chemotherapy and Targeted Agents Revamp Relapsed SCLC Management

The influx of novel treatment advances for SCLC also signals a shift away from the use of platinum rechallenge—a historical SOC—in the second-line setting. For instance, in a phase 2 basket trial (NCT02454972), data from which supported the FDA approval of lurbinectedin for the treatment of patients with metastatic SCLC, 44% of patients with a chemotherapy-free interval of at least 90 days had a duration of response of at least 6 months; this rate was 10% in patients with a chemotherapy-free interval of less than 90 days.

“Would that have happened with platinum rechallenge?” Jacob Sands, MD, asked. “Probably not better than that. We see improved outcomes with all cytotoxic [agents] in [patients] with platinum sensitivity. Lurbinectedin and some other options are less toxic than platinum rechallenge.”

Furthermore, findings from the phase 3 DeLLphi-304 trial (NCT05740566), which were presented at ASCO 2025, showed that second-line tarlatamab-dlle (Imdelltra) generated statistically significant and clinically meaningful OS benefits vs chemotherapy in patients with relapsed SCLC (Table 2).

 At median follow-ups of 11.2 months in the tarlatamab arm (n = 254) and 11.7 months in the chemotherapy arm (n = 255), patients who received tarlatamab achieved a median OS of 13.6 months vs 8.3 months for those who received chemotherapy (HR, 0.60; 95% CI, 0.47-0.77; 2-sided 

 The 6- and 12-month OS rates with tarlatamab were 76% and 53%, respectively. In the chemotherapy arm, these respective rates were 62% and 37%.

“Tarlatamab is the only therapy that has the potential for a long-term, durable response,” Lovly stated. “Why would I not give a patient tarlatamab, considering the other options that we have for the second line or beyond? Tarlatamab now should be the SOC for second-line SCLC. This requires an even larger team to coordinate the hospital admissions [and] the multiple clinical visits. This will change as we learn how to operationalize the drug better. However, the operational aspect should not prevent us from giving what we believe is the best drug to patients, so we have to make it work as a systems-based team that is not just a physician-based team, but also [includes] social workers, case management, [and] hospital administration to arrange the admissions.”

Now that multiple second-line treatment options are making their way into the SCLC management arena, the panelists emphasized that individual patient characteristics and multidisciplinary collaboration will increasingly factor into decision-making in this setting. For example, in DeLLphi-304, the OS benefit observed with tarlatamab extended to patients across several prespecified subgroups, including those with previous or current brain metastases (HR, 0.45; 95% CI, 0.31-0.65).

Furthermore, although the pivotal basket trial that led to the FDA approval of lurbinectedin for patients with relapsed SCLC did not include patients with brain metastases,

 data from the retrospective LURBICLIN study demonstrated that among a cohort of patients with SCLC who had received lurbinectedin in the second- or later-line setting, investigators observed no significant differences in lurbinectedin-related outcomes based on the presence of brain metastases.

 The median intracranial PFS was 3.1 months (95% CI, 2.6-4.1) in patients with baseline brain metastases and 8.8 months (95% CI, 4.9-not reached) in those without baseline brain metastases.

“It’s important, no matter which agent we choose for patients with or without a history of brain metastases, to be doing regular MRIs every 3 months to make sure if and when we see brain metastases develop, we can loop in our radiation oncology colleagues early to manage those brain metastases before [the patients] develop symptoms and [so we can] keep patients on systemic therapy,” Meador highlighted.

PRISM Trial Seeks to Optimize Durvalumab's Role in SCLC

As more agents enter the SCLC treatment paradigm, future research questions will revolve around optimal ways to combine and sequence these agents, particularly following progression on prior targeted therapies.

The phase 2 PRISM (SWOG S2409) trial (NCT06769126) plans to evaluate durvalumab alone vs in combination with novel biomarker-directed therapies (saruparib [AZD5305], ceralasertib [AZD6738], or monalizumab [formerly IPH2201]) as maintenance therapy in patients with ES-SCLC.

 The trial is enrolling patients 18 years and older who are either treatment naive and planning to receive first-line induction therapy with platinum plus etoposide and durvalumab, or pretreated with first-line induction therapy and have completed between 1 and 3 cycles of platinum and etoposide. Patients must not have prior exposure to immunotherapy other than durvalumab and must have adequate tumor tissue available. Those with untreated brain metastases must be asymptomatic and stable without steroids prior to random assignment.

Following tissue specimen testing to determine individual SCLC subtypes and treatment eligibility, patients will be assigned to 1 of 3 cohorts, then randomly assigned to 1 of 2 arms within their assigned cohort. The primary end points include screening success rate and PFS in all 3 cohorts. Key secondary end points across cohorts include safety, OS, SCLC subtype status, and SLFN11 expression status.

ADC Development Sets the Stage For Future SCLC Treatment Strategies

Moreover, the array of ADCs for SCLC is expanding. For instance, at a median follow-up of 15.3 months (range, 0.8-20.3), treatment with the investigational B7-H3–directed ADC ifinatamab deruxtecan at a dose of 12 mg/kg (n = 42) generated an overall response rate (ORR) of 54.8% (95% CI, 38.7%-70.2%) among heavily pretreated patients with ES-SCLC; all responses were partial.

“For the relapsed setting post tarlatamab or lurbinectedin or [other] FDA-approved agents, now we’re seeing ADCs, this trojan horse with an unassuming antibody chemotherapy payload that is introduced to the surface of the SCLC and brought in as a ticking time bomb to the SCLC to target [it], typically with a topoisomerase inhibitor payload,” Shields explained. “[ADCs are associated with] high ORRs in relapsed, heavily pretreated patients.”

DLL3 is another attractive target for the development of SCLC ADCs, the panelists agreed. The DLL3-targeted ADC ZL-1310 is under investigation in an ongoing, global phase 1 trial (NCT06179069) in patients with ES-SCLC.

 Updated data from the dose-escalation portion of the trial presented at ASCO 2025 showed an ORR of 68% and a disease control rate of 93% among 28 evaluable patients. The best ORRs among patients who had received 1 (n = 33), 2 (n = 26), and 3 or more (n = 15) prior lines of therapy were 49%, 27%, and 27%, respectively. Investigators observed responses across all tested dose levels and DLL3 expression levels. Additionally, among patients with brain metastases (n = 22), the ORR was 46%.

The panelists concluded their discussion by noting questions regarding the potential for and causes of acquired resistance with the serial use of therapies directed at the same target. With the ubiquitous use of the DLL3-targeted agent tarlatamab for all-comers with SCLC, the speakers emphasized that further research is necessary to determine how DLL3 expression changes over the course of the disease and in the presence of each agent. Although the SCLC treatment armamentarium is accumulating an array of novel agents, biomarker biology and target expression remain ripe points for further therapeutic evolution through innovative clinical research.

“There are more drugs in development for SCLC than there ever have been in the past,” Meador summarized. “Please refer your patients for trials, because the only way we’re going to advance the field is by continuing to get patients on trials, enroll on these studies, and learn. We cannot do that unless we’re getting patients onto studies.”

FDA approves durvalumab for limited-stage small cell lung cancer. FDA. December 4, 2024. Accessed June 20, 2025. http://bit.ly/4lfHOPY

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Recent advancements in small cell lung cancer (SCLC) treatment include immunotherapies, maintenance strategies, and antibody-drug conjugates (ADCs), emphasizing the importance of multidisciplinary collaboration. Durvalumab has been established as a standard of care for limited-stage SCLC, while both atezolizumab and durvalumab are key in extensive-stage SCLC. New data suggest lurbinectedin plus atezolizumab improves outcomes in first-line maintenance for extensive-stage SCLC. Novel agents like tarlatamab and ADCs are reshaping second-line treatment, with ongoing research focusing on optimizing combinations and sequencing of therapies.

Five experts gathered for the OncLive Peer Exchange to discuss SCLC data that continues to drive the evolving treatment paradigm.

Vol. 26/No. 8 | Oncology Live®

Federal Funding Cuts Spark Concern Over Future of Cancer Research and Care in United States

A New Era In Multiple Myeloma Treatment: Advances and Future Directions

Fc-Enhanced Agents May Expand Anti–CTLA-4 Approaches in GI Cancers

Genomic Tests for HR+/HER2– Early Breast Cancer Show Utility Beyond Predicting Prognosis

SCLC Data Drive Changes in First-Line Maintenance and Second-Line Care

Is It Time to Revisit How We Measure and Report the Toxicities of Antineoplastic Pharmaceutical Agents?