The continuous evolution of therapies for hormone receptor–positive/HER2- negative breast cancer has fueled investigators to evaluate HER2 expression further and data presented at the 2023 San Antonio Breast Cancer Symposium (SABCS) further ignited discussions surrounding CDK4/6 inhibitor use and the possibility of a new treatment for PIK3CA-mutant disease in this patient population. 

Updated data from clinical trials are shedding light on the role of agents such as ribociclib (Kisqali) and datopotamab deruxtecan (Dato-DXd; DS-1062a). The final invasive disease-free survival (iDFS) analysis of the phase 3 multicenter, open label NATALEE trial (NCT03701334), which enrolled patients with hormone receptor-positive/HER2-negative early breast cancer, revealed that ribociclib plus a nonsteroidal aromatase inhibitor continued to a produce a statistically significant improvement in iDFS vs a nonsteroidal aromatase inhibitor alone in key subgroups. Investigators noted that 78.3% of patients of patients (n = 1996/2549) had stopped therapy with ribociclib by the final iDFS analysis. However, overall survival (OS) data are not mature at this time.

“We need additional follow-up to look at the full impact of 3 years of ribociclib because even at the time of study presentation, a number of patients were still within the 3 years of ribociclib [treatment]. But it’s very reassuring to see the updated results, which continued to show that the curves continue to separate and that ribociclib plus endocrine therapy is superior to endocrine therapy alone,” Aditya Bardia, MD, MPH, an attending physician and director of the Breast Cancer Research Program at Massachusetts General Hospital, and associate professor of medicine at Harvard Medical School, both in Boston, said in an interview with OncologyLive. 

Diving into updates in the hormone receptor–positive/ HER2-negative breast cancer space during interviews with OncologyLive, investigators detailed how updates presented at SABCS are informing practice. 

Trial Showcases Findings Extending PFS Outcomes 

Meeting its dual primary progression-free survival (PFS) end point, findings from the phase 3, global, open-label, phase 3 TROPION-Breast01 trial (NCT05104866) revealed that Dato-DXd yielded a statistically significant and clinically meaningful improvement in PFS compared with investigator’s choice of chemotherapy in patients with previously treated unresectable or metastatic hormone receptor–positive/HER2-negative breast cancer. Patients who received Dato-DXd (n = 365) achieved a median PFS of 6.9 months vs 4.9 months in the chemotherapy arm (n = 367) by blinded independent central review (HR, 0.63; 95% CI, 0.52-0.76; P < .0001). The investigator- assessed 12-month PFS rates were 21.7% vs 9.9%, respectively.

The Trop-2 directed antibody- drug conjugate (ADC) also showcased a favorable safety profile vs chemotherapy. “Patients who received Dato-DXd had a lower incidence of grade 3 or higher adverse effects [AEs] compared with standard chemotherapy,” Bardia said. “[With] Dato-DXd, the most common AE [was] mucositis.” 

Bardia noted that the “unique” properties of Dato-DXd may contribute to this safety profile because the agent “has an optimized drug-to-antibody ratio and a stable linker that reduces off-target toxicity [that] is cleavable inside the tumor…. [Additionally], the payload is membrane permeable so it can address tumor heterogeneity.” 

Additionally, those who received Dato-DXd experienced a confirmed median time to deterioration (TTD) in terms of physical functioning of 12.5 months vs 6.2 months for patients in the chemotherapy arm (HR, 0.77; 95% CI, 0.59-1.01). The confirmed median TTD in terms of pain was 9.0 months vs 5.5 months, respectively (HR, 0.72; 95% CI, 0.55-0.94). The confirmed median TTD in terms of global health status/QOL was 9.0 months in the Dato-DXd arm compared with 4.8 months in the chemotherapy arm (HR, 0.76; 95% CI, 0.58-0.98).

“Dato-DXd is being evaluated in [first-line] metastatic triple-negative breast cancer in the phase 3 TROPION-Breast02 study [NCT05374512],” Bardia said, detailing next steps for the agent. “It’s also being evaluated in patients who have residual disease despite standard neoadjuvant therapy in [the phase 3] TROPION-Breast03 study [NCT05629585]. There’s a planned study in the neoadjuvant setting, [the phase 3] TROPIONBreast04 trial [NCT06112379], where patients will receive Dato- DXd as first therapy after diagnosis of localized triple-negative breast cancer,” he said.

Parasifal-Long Study Sheds Light on CDK4/6 Inhibitor Use

“There are now ample data to suggest that the [median] OS after treatment with palbociclib [Ibrance] approaches 5 and a half years. The OS of abemaciclib [Verzenio], even though it was not statistically significant from the phase 3 MONARCH 3 trial [NCT02246621], approached 5 and a half years, and the OS from ribociclib is 5 and a half years. It’s even more than that now that we have other agents like ADCs,” Adam M. Brufsky, MD, PhD, said in an interview with OncologyLive. Brufsky is a professor of medicine at the University of Pittsburgh School of Medicine and associate director of Clinical Investigation, associate chief of the Division of Hematology/ Oncology, and codirector of the Comprehensive Breast Cancer Center at the University of Pittsburgh Cancer Institute in Pennsylvania. 

Data from PARSIFAL-LONG, the 5-year extended follow-up of the phase 2 PARSIFAL trial (NCT02491983), demonstrated that patients with hormone receptor–positive/HER2-negative advanced breast cancer who received fulvestrant and palbociclib (n = 197) experienced a median OS of 68.5 months (95% CI, 54.3-81.6) compared with 61.9 months (95% CI, 55.7-71.3) for those treated with letrozole and palbociclib (n = 192; HR, 0.94; 95% CI, 0.72-1.23; P = .635).

“There was no difference [in OS] between the arms, but it was important to note in a trial designed for OS with endocrine-sensitive patients, the median OS was 65.4 months [in both cohorts combined], which is the same as ribociclib and the same as abemaciclib. To me, that says that all of the CDK4/6 inhibitors in the metastatic setting behave the same. The choice of CDK4/6 inhibitor in the first-line setting should be determined by the patient and the potential toxicities of the drug. Physicians can be comfortable giving any of those 3 [agents] in the first line,” Brufsky said. 

Brufsky noted that efforts are now centered on addressing the unmet need of determining why some patients do very well on CDK4/6 inhibitors in the first line, but others become endocrine resistant and progress within 12 months.

New Data May Inform Treatment of PIK3CA-Mutant Disease

Further, according to findings from the phase 3 INAVO120 study (NCT04191499), patients with PIK3CA-mutant hormone receptor–positive/ HER2-negative advanced breast cancer who experienced recurrence on or within 12 months of adjuvant endocrine therapy, inavolisib plus palbociclib and fulvestrant yielded a statistically significant and clinically meaningful improvement in PFS vs palbociclib and fulvestrant alone.

“These are very interesting data, and we have to wait a bit to see some updates,” Brufsky said. “This may also be a potential treatment up front with a PI3K inhibitor to treat the hard-to-treat, primarily endocrine-resistant [disease group]. That’s an unmet need.” 

The median PFS in the triplet arm (n = 161) was 15.0 months (95% CI, 11.3-20.5) vs 7.3 months (95% CI, 5.6-9.3) in the doublet arm (n = 164; HR, 0.43; 95% CI, 0.32-0.59; P < .0001) at a median follow-up of 21.3 months. The median OS was not estimable (NE; 95% CI, 27.3-NE) compared with 31.1 (95% CI, 22.3-NE), respectively (HR, 0.64; 95% CI, 0.43-0.97; P = .0338). Additionally, patients experienced a median duration of response of 18.4 months (95% CI, 10.4-22.2) in the inavolisib, palbociclib, and fulvestrant arm compared with 9.6 months (95% CI, 7.4-16.6) in the palbociclib and fulvestrant arm (HR, 0.57; 95% CI, 0.33-0.99).

“[The trial showed a doubling of PFS [and a] trend toward improvement in OS as well. The triplet combination was more efficacious [and] also has more toxicity, but there are AEs that we expect from PI3K inhibitors [such as] mucositis, hyperglycemia, [and] rash, [and] with palbociclib, neutropenia,” Bardia said. “It was good to see results of this triplet regimen in this setting, and if it is approved this would be the first approval for inavolisib.” 

Regarding safety, 88.3% of patients in the triplet arm and 82.1% of patients in the doublet arm experienced grade 3 to 4 AEs, and serious AEs occurred in 24.1% and 10.5% of patients, respectively. AEs led to discontinuation of treatment (6.8% vs 0.6%) and dose modification or interruption of treatment (82.7% vs 74.7%) in patients in the triplet vs doublet arms, respectively. Six patients in the investigative arm died due to AEs and 2 patients in the control arm died due to AEs.

The most common any-grade AEs were neutropenia (88.9% vs 90.7%), thrombocytopenia (48.1% vs 45.1%), stomatitis/mucosal inflammation (51.2% vs 26.5%), anemia (37.0% vs 36.4%), hyperglycemia (58.6% vs 8.6%), diarrhea (48.1% vs 16.0%), and nausea (27.8% vs 16.7%).

Evaluating HER2 Expression in Advanced Disease

The retrospective, real-world RELIEVE study collected data from patients with metastatic breast cancer of any HER2 or hormone receptor status who received fam-trastuzumab deruxtecan- nxki (Enhertu) at Dana-Farber Cancer Institute in Boston, Massachusetts, or Duke Cancer Institute in Durham, North Carolina. A total of 191 patients with HER2-positive disease (n = 126; 66%), HER2-low (n = 44; 23%), or HER2-0 (n = 21; 11%) were included. Most had hormone receptor–positive (57%) disease, and patients had received a median of 2 (range, 0-9) prior lines of chemotherapy.

The median time to next treatment (TTNT) was 10.4 months, 7.6 months, and 3.7 months in the HER2-positive, HER2-low, and HER2-0 groups, respectively. Additionally, the novel ctDNA test DNADX predicted the real-world activity of trastuzumab deruxtecan. Fifty-one patients with any HER2 status and a tumor fraction value of greater than 1% were evaluated. The DNADX HER2 signature results showed the median TTNT for patients with HER2 signature-high disease was 10 months, HER2 signature-medium disease was 7 months, and HER2 signature-low was 5 months.

Sara M. Tolaney, MD, MPH, explained in an interview with OncologyLive that HER2-low disease is dynamic. “For example, you can start out with a tumor that’s HER2-0 that becomes HER2-low and then you go on [to give a patient] trastuzumab deruxtecan or [vice versa],” Tolaney said. “Does it matter what the dynamics [are] with relationship to efficacy? We found that if a patient was consistently HER2-low, whether that was HER2-low on primary [diagnosis] and HER2- low in the metastatic setting, for example, PFS was better than if you went from being HER2- low to HER2-0 or [vice versa]. It makes sense that if [patients] are stably HER2-low, [their] disease control will be better.” 

Tolaney is chief of the Division of Breast Oncology, associate director at Susan F. Smith Center for Women’s Cancers, and a senior physician at Dana-Farber Cancer Institute, as well as an associate professor of Medicine at Harvard Medical School. 

The median TTNT was 9.4 months for those with stable HER2-low disease (n = 21) who received trastuzumab deruxtecan, 5.6 months for those with HER2-0 disease at primary diagnosis and HER2-low disease at metastasis (n = 21), and 3 months for those with HER2-low disease at primary diagnosis and HER2-0 disease at metastasis (n = 10).

“We see HER2-low status switching and being quite dynamic, and understanding how that impacts efficacy is useful,” Tolaney said. “As we learn more about trastuzumab deruxtecan, hopefully we’ll be able to figure out who’s going to benefit so that we can tailor therapy more. This is going to get more important as we see more ADCs get into this space. We’re going to need to figure out what is the optimal ADC to use first, and maybe better understanding these biomarker predictors will help us get there.”

Articles

Investigators continue to evaluate HER2 expression as well as CDK4/6 inhibitor use for hormone receptor–positive/HER2-negative breast cancer.


Laying the Foundation for an Improved HR+/ HER2- Breast Cancer Treatment Paradigm

Dr Bartsch on the TUXEDO-1 Trial of T-DXd in HER2+ Breast Cancer With Brain Metastases

Rupert Bartsch, MD, associate professor, Department of Medicine, Division of Oncology, Medical University of Vienna, discusses findings from the final analysis of the phase 2 TUXEDO-1 trial (NCT04752059) of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in patients with HER2-positive breast cancer with active brain metastases, which were presented during the 2023 San Antonio Breast Cancer Symposium.

The single-arm, prospective, single-center TUXEDO-1 trial enrolled adult patients with HER2-positive breast cancer with active brain metastases who had received prior treatment with trastuzumab (Herceptin) and pertuzumab (Perjeta), had an ECOG performance status of 0 or 1, and were not indicated for immediate local therapy. Patients received T-DXd until disease progression, unacceptable toxicity, or trial withdrawal for any other reason.

At a median follow-up of 26.5 months, the median progression-free survival (PFS) with T-DXd was 21 months (95% CI, 13.3-not reached [NR]). This median PFS was similar to that reported in the retrospective exploratory pooled analysis of T-DXd activity in patients with HER2-positive metastatic breast cancer with brain metastases who were enrolled in the phase 2 DESTINY-Breast01 (NCT03248492), phase 3 DESTINY-Breast02 (NCT03523585), and phase 3 DESTINY-Breast03 (NCT03529110) trials. In this analysis, which was presented at the 2023 ESMO Congress, the median central nervous system PFS per blinded independent central review was 18.5 months (95% CI, 13.6-23.3) with T-DXd vs 4.0 months (95% CI, 2.7-5.7) with a comparator (HR, 0.1919; 95% CI, 0.1060-0.3473).

The median overall survival in TUXEDO-1 was NR (95% CI, 22.2-NR). Bartsch notes the potential for phase 2 bias in this finding, as the patient population enrolled in TUXEDO-1 may have had relatively low-risk disease despite the presence of brain metastases. However, these survival data indicate that systemic therapies, including T-DXd, can effectively manage breast cancer brain metastases, Bartsch emphasizes. Tucatinib (Tukysa) is another effective agent for treating patients with brain metastases, as evidenced in the phase 2 HER2CLIMB trial (NCT02614794), Bartsch concludes.

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Rupert Bartsch, MD, discusses findings from the final analysis of the phase 2 TUXEDO-1 trial of trastuzumab deruxtecan in patients with HER2-positive breast cancer with active brain metastases.

Dr Huppert on Sequential Treatment with T-DXd and Sacituzumab Govitecan in HER2-Low Breast Cancer

Laura A. Huppert, MD, breast medical oncologist, assistant professor, University of California, San Francisco School of Medicine, discusses the impact of sequential treatment with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) and sacituzumab govitecan-hziy (Trodelvy) on outcomes in patients with HER2-low metastatic breast cancer, according to findings from a retrospective analysis.

A multicenter cohort study was conducted to assess the efficacy and safety of these antibody-drug conjugates (ADCs) when used in sequence in a real-world setting. Patients with hormone receptor (HR)–positive or HR-negative, HER2-low breast cancer who had received both T-DXd and sacituzumab govitecan as single agents between 2020 and 2023 were enrolled onto the study. Patients may have received the agents in either order, with or without intervening therapies. A total of 84 patients were included in the analysis, 56 of whom had HR-positive, HER2-low disease.

In the HR-positive cohort, 42.9% of patients received sacituzumab govitecan before T-DXd, Huppert states. These patients had a median of 3 prior lines of therapy (range, 0-9), including 2 prior lines of chemotherapy (range, 0-5), Huppert details. The median real-world progression-free survival in this cohort was 8.0 months with sacituzumab govitecan as the first ADC administered in the sequence and 3.7 months with T-DXd as the second ADC, she reports. The median overall survival was 22.8 months with sacituzumab govitecan and 7.8 months with T-DXd, Huppert adds. Notably, the real-world median PFS and OS with T-DXd followed by sacituzumab govitecan were undetermined in patients with HR-negative disease.

Generally, investigators expect that patients will spend a shorter time on treatment with the second ADC compared with the first, especially as patients progress through lines of treatment, Huppert continues. Although most patients in this study responded longer to their first ADC, some experienced a longer duration of response on their second therapy, she notes. This finding underscores the importance of understanding the mechanisms of resistance and predictors of response with these agents, Huppert explains. Accordingly, both ADCs should be utilized in clinic, as patients can have varying responses to different therapies, and predicting individual outcomes with each agent remains a challenge, she emphasizes. Overall, these data emphasize the need for continued research into the factors influencing responses to ADCs in breast cancer and the potential benefits of sequential ADC therapies, Huppert concludes.

Sponsored in part by Daiichi Sankyo. Content independently developed by OncLive®

Laura A. Huppert, MD, discusses the impact of sequential treatment with fam-trastuzumab deruxtecan-nxki and sacituzumab govitecan-hziy on outcomes in patients with HER2-low metastatic breast cancer, according to findings from a retrospective analysis.

T-DXd in Patients With HER2+ Breast Cancer With Brain Metastases and Leptomeningeal Disease

Dr Niikura on T-DXd in Patients With HER2+ Breast Cancer With Brain Metastases and Leptomeningeal Disease

Naoki Niikura, MD, PhD, member, Department of Breast Oncology, Tokai University School of Medicine, discusses the impact of treatment with fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in patients with HER2-positive breast cancer withbrain metastases and/or leptomeningeal disease, as evaluated in the real-world ROSET-BM study (UMIN000044995) in Japan. 

 in October 2023, and investigators found that T-DXd was associated with intracranial efficacy in this high-risk patient population. Furthermore, results indicated that among patients evaluated independently for intracranial response (n = 51), there was a 62.7% intracranial overall response rate (95% CI, 48.1%-75.9%). All responders had partial responses in the brain, with rates of stable disease and progressive disease at 31.4% and 5.9%, respectively. The intracranial clinical benefit rate at 6 months stood at 70.6% (95% CI, 56.2%-82.5%).

Additional data revealed that the entire study population achieved a median progression-free survival (PFS) of 16.1 months (95% CI, 12.0-not reached [NR]), with 6- and 12-month PFS rates of 77.0% (95% CI, 67.4%-84.1%) and 61.9% (95% CI, 50.8%-71.1%), respectively. The median overall survival was NR (95% CI, 16.1%-NR), and the median time to treatment failure was 9.7 months (95% CI, 6.3-13.0).

Niikura goes on to say that the National Comprehensive Cancer Network guidelines for managing HER2-positive breast cancer with brain metastases have been updated and now recommend the phase 2 HER2CLIMB trial (NCT02614794) regimen as the preferred choice. T-DXd is among other recommended regimens for the treatment of this patient population, he says. T-DXd is associated with efficacy in patients with breast cancer brain metastases, regardless of the status of the metastases or the presence of leptomeningeal disease, Niikura explains.

T-DXd is also associated with a manageable adverse effect profile and may provide survival benefits for patients with a poor prognosis, such as those with leptomeningeal disease, he continues. In ROSET-BM, a small number of patients with breast cancer with leptomeningeal disease achieved disease control with T-DXd. These findings indicate that although there is currently no standard treatment for patients with breast cancer with leptomeningeal disease, T-DXd is considered a therapeutic option for patients with this condition, Niikura concludes.

Dr Niikura reports speaker’s bureau participation with AstraZeneca, Chugai, Daiichi-Sankyo, Pfizer, Eli Lilly, and MSD; as well as grant-research support from Chugai, Daiichi-Sankyo, Pfizer, Eisai, Mochida, and Novartis.

Naoki Niikura, MD, PhD, discusses the impact of treatment with trastuzumab deruxtecan in patients with HER2-positive breast cancer with brain metastases and/or leptomeningeal disease, as evaluated in the real-world ROSET-BM study in Japan.  


 Treating Patients With HER2+ Breast Cancer and Leptomeningeal Carcinomatosis 

Dr Vaz Batista on Treating Patients With HER2+ Breast Cancer and Leptomeningeal Carcinomatosis 

Marta Vaz Batista, MD, medical oncologist, Hospital Fernando Fonseca, discusses the efficacy of fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in patients with HER2-positive or HER2-low advanced breast cancer and pathologically confirmed leptomeningeal carcinomatosis, as evaluated in cohort 5 of the phase 2 DEBBRAH study (NCT04420598).

Results from this patient subgroup analysis

the 2023 San Antonio Breast Cancer Symposium

. Forty-one patients across Spain and Portugal were enrolled into the single-arm, open-label, 5-cohort study, 7 of whom were enrolled into cohort 5, where treatment with T-DXd resulted in clinical responses. At the meeting, investigators shared that the median overall survival (OS) with T-DXd in cohort 5 was 13.3 months (95% CI, 2.5-not reached; 

 <.001). Notably, the 16-week OS rate was 86% (95% CI, 33%-98%), and the 24-week OS rate was 71% (95% CI, 26%-92%).

The primary aim of evaluating patients with HER2-positive breast cancer and leptomeningeal carcinomatosis in cohort 5 of DEBBRAH was to assess OS with T-DXd due to the recognized poor prognosis of this patient population, Vaz Batista begins. Quantifying additional treatment options for this patient subgroup, where the current standards of care are associated with limited efficacy, has proven challenging, she notes.

Although leptomeningeal carcinomatosis is a terminal event in patients with breast cancer, in this cohort of 7 patients, 2 patients were still undergoing treatment at the data cutoff, indicating notable progress in progression-free survival for this population, she continues. Patients with leptomeningeal carcinomatosis have unmet needs, as treatment strategies remain uncertain upon the development of this metastasis, Vaz Batista emphasizes. Although retrospective analyses with various drugs have been explored, this trial represents the first prospective phase 2 study demonstrating the efficacy of T-DXd in patients with leptomeningeal carcinomatosis, she states.

This trial, despite its phase 2 nature, stands as a significant contribution to clinical practice, showcasing promising outcomes with T-DXd in this difficult-to-treat patient population, Vaz Batista says. Conducting phase 3 trials in this patient population in the foreseeable future may be impractical due to the infrequency of leptomeningeal carcinomatosis cases, Vaz Batista concludes.

Sponsored in part by Daiichi Sankyo. Content independently developed by OncLive

Marta Vaz Batista, MD, discusses the efficacy of trastuzumab deruxtecan in patients with HER2-positive or HER2-low advanced breast cancer and pathologically confirmed leptomeningeal carcinomatosis, as evaluated in cohort 5 of the phase 2 DEBBRAH study.

Dr Bardia on the Efficacy and Safety of Dato-DXd in HR+/HER2– Breast Cancer

Aditya Bardia, MD, MPH, attending physician, medical oncology, Massachusetts General Hospital; associate professor, medicine, Harvard Medical School, discusses key efficacy results from the phase 3 TROPION-Breast01 trial (NCT05104866) of datopotamab deruxtecan (Dato-DXd) in hormone receptor–positive, HER2-negative breast cancer.

This open-label, global study enrolled patients who had received 1 or 2 prior lines of chemotherapy in the inoperable or metastatic setting. Patients were randomly assigned 1:1 to receive either the Trop-2–directed antibody-drug conjugate or investigator’s choice of chemotherapy.

 show that the trial met its dual primary end point of improved progression-free survival (PFS) vs standard chemotherapy in this population, Bardia reports. At the data cutoff date of July 17, 2023, Dato-DXd produced a median PFS of 6.9 months vs 4.9 months in the chemotherapy arm by blinded independent central review (HR, 0.63; 95% CI, 0.52-0.76; 

 < .0001). In the Dato-DXd arm, the 6-, 9-, and 12-month PFS rates according to investigator assessment in were 55.2%, 34.7%, and 21.7%, respectively. Respective rates were 36.9%, 20.9%, and 9.9% in the chemotherapy arm.

Moreover, Dato-DXd provided a PFS benefit over chemotherapy regardless of the presence of brain metastases or prior treatment with a CDK4/6 inhibitor, Bardia states. In terms of time to treatment failure (TFST), patients in the Dato-DXd arm experienced a median TFST of 8.2 months (95% CI, 7.4-8.9) compared with 5.0 months (95% CI, 4.6-5.7) in the chemotherapy arm (HR, 0.53; 95% CI, 0.45-0.64), he details.

Additionally, Dato-DXd showed advantages in time to deterioration (TTD) in global health status/quality of life over chemotherapy, Bardia continues. The median TTD at first instance favored Dato-DXd in terms of physical functioning (HR, 0.77; 95% CI, 0.61-0.99), and pain (HR, 0.85; 95% CI, 0.68-1.07).

Safety analysis revealed that patients treated with Dato-DXD experienced a lower incidence of grade 3 or higher treatment-related adverse effects (TRAEs; 21%) vs chemotherapy (45%), Bardia says. However, any-grade TRAEs occurred in the Dato-DXd and chemotherapy arms at rates of 94% vs 86%, respectively, he notes, adding that this agent is commonly associated with AEs such as mucositis.

Aditya Bardia, MD, MPH, discusses key efficacy results from the phase 3 TROPION-Breast01 trial of datopotamab deruxtecan in hormone receptor–positive, HER2-negative breast cancer.


Dr Bardia on the Efficacy and Safety of Dato-DXd in HR+/HER2– Breast Cancer  

Dr Tolaney on the Real-World Efficacy of T-DXd in HER2+ or HER2-Low Breast Cancer

Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, Susan F. Smith Center for Women's Cancers, associate director, Susan F. Smith Center for Women's Cancers, senior physician, Dana-Farber Cancer Institute, associate professor of Medicine, Harvard Medical School, discusses the real-world efficacy of fam-trastuzumab deruxtecan (T-DXd; Enhertu) in patients with HER2-positive or HER2-low metastatic breast cancer, including patients who experienced changes in HER2 status during the treatment course.

The RELIEVE study collected data from patients in the United States with advanced breast cancer treated with T-DXd between July 2017 and February 2022 at Dana-Farber Cancer Institute and between March 2020 and April 2022 at Duke Cancer Center, Tolaney begins. Key study end points included time to next treatment (TTNT), progression-free survival (PFS), overall survival (OS), toxicities, and TTNT with post-T-DXd regimens.

 showed that T-DXd significantly prolonged time-to-next treatment in this population, producing the longest TTNT in patients with HER2-positive disease or with stable HER2-low disease in the primary and metastatic setting.

 < .001), the median TTNT after T-DXd was 10.4 months, 7.6 months, and 3.7 months in 191 real-world patients with HER2-positive, HER2-low, and HER2-0 status, respectively, Tolaney reports.

The study also explored whether dynamic HER2 status impacted outcomes with T-DXd. Patients consistently categorized as HER2-low both in the primary and metastatic settings experienced more prolonged outcomes vs those with changing status, Tolaney states. Patients experiencing a change in HER2 expression from HER2-low to HER2-0 had a shorter median TTNT of 3.0 months vs 5.6 months for those transitioning from HER2-0 to HER2-low, and 9.4 months for stable HER2-low expression (

These variations indicate that changing HER2 status did influence patient benefit from T-DXd, with a shift from HER2-low to HER2-0 correlating with a shorter response. Given the dynamic nature of HER2 status, this finding reflects the importance of understanding how such fluctuations impact efficacy, Tolaney concludes.

Sara M. Tolaney, MD, MPH, discusses the real-world efficacy of fam-trastuzumab deruxtecan in patients with HER2-positive or HER2-low metastatic breast cancer, including patients who experienced changes in HER2 status during the treatment course.

Reviewing Key Updates in the Realm of Breast Cancer | Supplements and Featured Publications

Laying the Foundation for an Improved HR+/ HER2- Breast Cancer Treatment Paradigm

Dr Bartsch on the TUXEDO-1 Trial of T-DXd in HER2+ Breast Cancer With Brain Metastases

Dr Huppert on Sequential Treatment with T-DXd and Sacituzumab Govitecan in HER2-Low Breast Cancer

Dr Niikura on T-DXd in Patients With HER2+ Breast Cancer With Brain Metastases and Leptomeningeal Disease

Dr Vaz Batista on Treating Patients With HER2+ Breast Cancer and Leptomeningeal Carcinomatosis

Dr Bardia on the Efficacy and Safety of Dato-DXd in HR+/HER2– Breast Cancer

Dr Tolaney on the Real-World Efficacy of T-DXd in HER2+ or HER2-Low Breast Cancer