Francisco J. Esteva, MD, PhD, interim chief, Division of Hematology/Oncology, chief, Breast Medical Oncology, Lenox Hill Hospital, director, Breast Medical Oncology, Northwell Health, discusses the impact of the phase 2 MAINTAIN study (NCT02632045) of treatment with ribociclib (Kisqali) following progression on CDK4/6 inhibition in patients with hormone receptor (HR)–positive, HER2-negative breast cancer.

In the MAINTAIN trial, it's noteworthy that most patients were initially administered palbociclib (Ibrance), and upon disease progression, patients switched endocrine therapy from the endocrine therapy they used before random assignment in the trial and were randomly assigned to receive either ribociclib or placebo, Esteva begins. There was a statistically significant enhancement in progression-free survival (PFS) for those who continued with the CDK4/6 inhibitor. However, it's essential to highlight that 86.5% of the patients in the study initially received palbociclib and then transitioned to ribociclib, which adds a layer of complexity to the interpretation of these results, Esteva emphasizes. Other studies have explored the continuation of palbociclib upon progression, and in those cases, there was no observed improvement in PFS, he explains.

This discrepancy in findings between MAINTAIN and other trials introduces a degree of uncertainty and potential conflict in the data, Esteva expands. One explanation for these differing outcomes could be the inherent differences between CDK4/6 inhibitors themselves, although the limited size of the studies prevents investigators from drawing definitive conclusions in this regard, he states.

The insights derived from the MAINTAIN study suggest that continuing ribociclib following initial treatment with palbociclib is not an unusual strategy, Esteva notes. However, it's essential to recognize that the reverse scenario, where patients initially receive ribociclib and continue with ribociclib upon progression, lacks a substantial body of supportive data, he continues. The evolving landscape of breast cancer treatment introduces additional therapeutic strategies, such as assessing patients with 

 mutations and exploring alternative treatments such as PI3K inhibitors and AKT inhibitors, Esteva says. As these treatments become more available, the future promises a broader array of therapeutic choices for patients with breast cancer, potentially further complicating the decision-making process in the clinical setting, he concludes.

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Francisco J. Esteva, MD, PhD, discusses the impact of the phase 2 MAINTAIN study of treatment with ribociclib following progression on CDK4/6 inhibition in patients with hormone receptor-positive, HER2-negative breast cancer.


Dr Esteva on the Impact of the MAINTAIN Trial in HR+/HER2– Breast Cancer

Francisco Javier Esteva, MD, PhD, chief, Breast Medical Oncology, Northwell Health Cancer Institute, discusses therapeutic developments for patients with HER2-positive breast cancer.

Historically, patients with HER2-positive breast cancer have poor prognoses, according to Esteva. With the development of drugs such as trastuzumab (Herceptin), pertuzumab (Perjeta), neratinib (Nerlynx), and ado-trastuzumab emtansine (T-DM1; Kadcyla), these patients now have significantly improved outcomes. However, it is important to understand how to sequence and combine these agents to derive the most benefit, Esteva says.

Incorporating neoadjuvant therapy into the treatment plan is important for patients with high-risk, early-stage breast cancer, Esteva explains. Once patients who do not achieve a pathologic complete response to this approach are identified, additional therapies can be used to improve outcomes, Esteva concludes. 

Francisco Javier Esteva, MD, PhD, discusses therapeutic developments for patients with HER2-positive breast cancer.

Francisco Esteva, MD, PhD

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Dr Esteva on the Impact of the MAINTAIN Trial in HR+/HER2– Breast Cancer

Dr. Esteva on Therapeutic Developments in HER2+ Breast Cancer