New recommendations for treating advanced breast cancer, coming from a panel of experts at the Advanced Breast Cancer (ABC) Sixth International Consensus Conference (ABC6), were recently published.1 The report highlights advances that have resulted in robust improvements in overall survival for this malignancy, according to Fatima Cardoso, MD, Chair of the ABC6 conference and the ABC Global Alliance and Director of the Breast Unit of the Champalimaud Cancer Centre, Lisbon.
A key objective of the ABC conferences, delineated in the ABC Global Charter, is to double the survival among patients with advanced breast cancer by 2025.2 This is starting to happen. “We have made a major step toward our goal of doubling average survival times for patients, because we have now achieved this in two of three subtypes of advanced breast cancer,” Dr. Cardoso said.
Fatima Cardoso, MD
Focus on HER2-Positive Advanced Disease
The biggest strides of late have been made in HER2-positive advanced breast cancer. The CLEOPATRA study demonstrated a median overall survival of about 5 years with dual HER2 blockade (trastuzumab and pertuzumab),3 but newer drugs have further boosted these improved outcomes, Dr. Cardoso noted. These agents include trastuzumab emtansine (T-DM1), fam-trastuzumab deruxtecan-nxki (T-DXd), and tucatinib. An overall survival benefit has been shown with T-DM1 and tucatinib and is expected to emerge with T-DXd as well, based on a very strong progression-free survival benefit.
“In our clinical practice, we see that our patients with HER2-positive metastatic disease may live 10 years or longer, with good quality of life,” she continued.
With so many effective agents, oncologists also need guidance on sequencing, and the new guidelines offer recommendations. They emphasize the need to continue HER2 blockade past disease progression, either by switching to a new agent or continuing trastuzumab. This concept breaks with the conventional paradigm in oncology, which is to discontinue the drug on which a patient has experienced disease progression, she pointed out.
The ABC consensus panel is emphasizing this point because not all patients are offered this life-prolonging treatment. “And it’s not just in low-to-middle-income countries,” Dr. Cardoso stated. “We don’t have large randomized controlled trials showing this, but we have a multitude of data making it clear that continued treatment should not be denied to patients—and it is being denied, all over the world,” Dr. Cardoso said in an interview with The ASCO Post. One of the most important missions of the ABC Global Alliance, and one of Dr. Cardoso’s personal passions, is to increase accessibility and affordability of effective treatments.
Hormone Receptor–Positive Disease: CDK4/6 Inhibitors
Improvement in overall survival has also recently been reported for hormone receptor–positive advanced breast cancer treated with a cyclin-dependent kinases 4/6 (CDK4/6) inhibitor. As reported at the European Society for Medical Oncology (ESMO) Congress 2021, first-line treatment with ribociclib plus letrozole led to a median overall survival of 63.9 months, compared with 51.4 months with letrozole alone—a 24% reduction in risk (P = .004) in the MONALEESA-2 trial.4 This is the longest median survival reported to date in any advanced breast cancer phase III clinical trial. In addition, widespread benefit for ribociclib across multiple subgroups of patients with hormone receptor–positive, HER2-negative breast cancer was reported at the 2021 San Antonio Breast Cancer Symposium.5,6
“We now have a median overall survival of 5 years. For the first time, we can speak about hope for these patients, not just wishful thinking,” said Dr. Cardoso.
Triple-Negative Disease
Although the best outcomes for this subtype have still not substantially improved overall survival, new drugs are making a difference, such as the antibody-drug conjugate sacituzumab govitecan-hziy, which was added to the recommendations for treatment. The checkpoint inhibitor pembrolizumab has been in the guidelines for several years.
“Survival has also improved for patients with triple-negative disease, but we need to do more for these patients, especially as it tends to affect younger people who often have young children to care for,” she said. Dr. Cardoso also advocates for overall survival to be the primary endpoint in clinical trials, which she explains is far more meaningful for the patients than progression-free survival.
Patients as Peers
Finally, Dr. Cardoso explained that the ABC conference is unique among guideline-issuing organizations by involving experts from all five continents and by including “patients as peers … giving them the same importance as others.” Patient advocates are expressly positioned to weigh in on issues of quality of life, access, and affordability, she said. In the end, the panel’s recommendations are always “based on science and on what truly matters to patients.”
DISCLOSURE: Dr. Cardoso has served as a consultant for Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Debiopharm, Eisai, GE Oncology, Genentech, Gilead, GlaxoSmithKline, IQVIA, Macrogenics, Medscape, Merck Sharp & Dohme, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, prIME Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva, and Touchime.
REFERENCES
1. Wuerstlein R, Cardoso F, Haidinger R: Expert discussion: Highlights from ABC6: Bridging the gap and insights in this first virtual ABC conference and from 10 years ABC consensus. Breast Care 17:107-112, 2022.
2. ABC Global Alliance: ABC Global Charter. Available at https://www.abcglobalalliance.org/abc-global-charter/. Accessed February 15, 2022.
3. Swain SM, Miles D, Kim SB, et al: Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol 21:519-530, 2020.
4. Hortobagyi GN, Stemmer SM, Burris III HA, et al: Overall survival results from the phase III MONALEESA-2 trial of postmenopausal patients with hormone receptor positive/human epidermal growth factor receptor 2 negative advanced breast cancer treated with endocrine therapy ± ribociclib. ESMO Congress 2021. Abstract LBA17_PR. Presented September 19, 2021.
5. O’Shaughnessy J, Stemmer SM, Burris HA, et al: Overall survival subgroup analysis by metastatic site from the phase 3 MONALEESA-2 study of first-line ribociclib + letrozole in postmenopausal patients with HR+/HER2– advanced breast cancer. 2021 San Antonio Breast Cancer Symposium. Abstract GS2-01. Presented December 8, 2021.
6. Carey LA, Solovieff N, Andre F, et al: Correlative analysis of overall survival by intrinsic subtype across MONALEESA-2, -3, and -7 studies of ribociclib + endocrine therapy in patients with HR+/HER2– advanced breast cancer. 2021 San Antonio Breast Cancer Symposium. Abstract GS2-00. Presented December 8, 2021.
