Etienne Brain, MD, PhD, on Breast Cancer: Adjuvant Endocrine Therapy With or Without Chemotherapy in Older Patients
2022 ASCO Annual Meeting
Etienne Brain, MD, PhD, of the Institut Curie, discusses phase III findings from the Unicancer ASTER 70s trial, in which patients aged 70 or older with estrogen receptor–positive, HER2-negative breast cancer and a high genomic grade index received adjuvant endocrine therapy with or without chemotherapy. The data did not find a statistically significant overall survival benefit with this treatment after surgery (Abstract 500).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
ASTER 70s study is a landmark study, which has been conducted in older women with luminal breast cancer in adjuvant setting questioning the addition of chemotherapy to endocrine treatment. The rationale behind is that the literature is very limited in terms of data published for the use of adjuvant chemotherapy in this situation in older ones. Multimorbidity competes with cancer on outcome and therapeutic ratio is also more narrow because there are higher risk of side effects in this population.
This trial screened near 2000 patients with the genomic grade index, the GGI, to assess the aggressivity of the disease and to spare the burden of chemotherapy in those patients with low-GGI tumor, while those with a high-GGI tumor were randomized between endocrine treatment alone as a standard arm versus chemotherapy followed by endocrine treatment. Near 2000 patients enrolled, 1,100 randomized between the two arms.
This trial shows, on the primary endpoint, which was overall survival by intent-to-treat analysis, that chemotherapy doesn't add a significant benefit in addition to endocrine treatment. That's the first message of caution from this study. Second one is that we can look at different subgroups and perform also the analysis according to the per protocol concept. This modifies or brings a nuance in the results, but I would say that the final potential benefit on overall survival in this case remains marginal. And in this population of older women, it is a key point and a double cautious message.
The next step for this study will be to try to improve the discriminative capacity of this kind of signature to identify those who could benefit still from chemotherapy, despite these global message and results on overall survival. This will be certainly possible with the use of the mass and the volume of data which has been collected in the randomized groups in this study, because there was a longitudinal collection of geriatric data, quality of life data, and treatment acceptability socioeconomic data, which will be very helpful to modelize differently, the prognosis of these ladies.
That's in the near future, and I think what brings the most in terms of information ASTER 70s, is that on the provisor that you change a bit of rules for inclusion criteria, because in this study we had very flexible inclusion criteria, we made a focus on quality of life and we use a single informed consent for screening and randomization, on the provisor that you facilitate or you simplify the processes, you can run large studies in a vast population, which is very often not considered for clinical trials left behind.
Ann H. Partridge, MD, MPH, of Dana-Farber Cancer Institute, and Véronique Diéras, MD, of the Centre Eugène Marquis, discuss the many challenges posed by next-generation antibody-drug conjugates (ADCs). They include side effects such as hematotoxicity, gastrointestinal toxicities, and interstitial lung disease; tumor targeting and payload release; drug resistance; and the urgent need to understand ADCs’ mechanisms of action to better sequence and combine drugs.
Stephanie Walker, a former nurse and current activist with the Metastatic Breast Cancer Alliance, discusses findings from the BECOME project (Black Experience of Clinical Trials and Opportunities for Meaningful Engagement). They show that, even though Black patients comprise between 4% and 6% of all clinical trial participants, Black women with metastatic breast cancer are willing to consider taking part if steps were taken to increase their awareness, build trust through clear communication with health-care providers, involve people of shared racial/ethnic identity and health experience, and help patients find and access trials (Abstract 1014).
Maxwell Oluwole Akanbi, MD, PhD, of McLaren Regional Medical Center, discusses the study he conducted, using the SEER database, to evaluate the impact of lung cancer screening recommendations on low-dose CT scanning. The data suggest that guidelines from the U.S. Preventive Services Task Force led to a more rapid decline in the incidence of advanced disease in the United States, especially among minority populations (Abstract 10506).
Jonathan E. Rosenberg, MD, of Memorial Sloan Kettering Cancer Center, and Thomas Powles, MD, PhD, of Barts Health NHS Trust, Queen Mary University of London, discuss phase III findings from the KEYNOTE-426 trial, which appear to support the long-term benefit of pembrolizumab plus axitinib for first-line treatment of patients with advanced clear cell renal cell carcinoma (Abstract 4513).
Ursula A. Matulonis, MD, of Dana-Farber Cancer Institute, and Ignace Vergote, MD, PhD, of Belgium’s University Hospitals Leuven, discuss interim safety and efficacy results from a third dose-expansion cohort evaluating first-line tisotumab vedotin-tftv plus pembrolizumab in patients with recurrent or metastatic cervical cancer. Data on the combination showed durable antitumor activity with a manageable safety profile (Abstract 5507).