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SABCS 2022 | RIGHT Choice: ribociclib + ET vs combo chemo in aggressive HR+/HER2− advanced breast cancer

Stephanie Graff, MD, Lifespan Cancer Institute and Brown University, Providence, RI, provides an overview of the Phase II RIGHT Choice (NCT03839823) study randomizing patients with high-risk, metastatic HR-posiitve breast cancer to receive either ribociclib plus goserelin acetate with hormonal therapy versus combination chemotherapy. Patient had either visceral crisis, high-burden visceral disease, or rapidly progressive breast cancer. The primary endpoint was progression-free survival (PFS). Median PFS was 24 months with ribociclib plus goserelin acetate with hormonal therapy versus 12 months with chemotherapy. Time to response was slightly faster with chemotherapy. This interview took place at the San Antonio Breast Cancer Symposium (SABCS) 2022 in San Antonio, TX.

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Transcript (edited for clarity)

RIGHT Choice was a study largely done outside of the United States, randomizing patients with high-risk metastatic hormone receptor-positive breast cancer. Specifically, the study was looking at patients who either had visceral crisis, high burden visceral disease, or rapidly progressive breast cancer, and it randomized those patients to either chemotherapy or ribociclib in combination with endocrine therapy...

RIGHT Choice was a study largely done outside of the United States, randomizing patients with high-risk metastatic hormone receptor-positive breast cancer. Specifically, the study was looking at patients who either had visceral crisis, high burden visceral disease, or rapidly progressive breast cancer, and it randomized those patients to either chemotherapy or ribociclib in combination with endocrine therapy. And what’s interesting is that, although definitions like visceral crisis and rapidly progressive disease, we all think as oncologists are clearly defined subsets, are also a little subjective. So, one of my criticisms of the trial is it’s hard to tell, looking at a spreadsheet on a presentation really how sick those patients were. But we know when we compare to the other trials that have been done in the CDK4/6 inhibitor landscape where many of the patients had bone only disease, for example, that this was a much sicker, heavier disease burden population that has previously been studied with CDK4/6 inhibitors.

It also was compared to chemotherapy, which isn’t something that we’ve seen readily in the CDK4/6 inhibitor landscape or environment. The trial median age of accrual was 44, which also tells us that this was a much younger population than we have historically seen participating in the CDK4/6 inhibitor studies. So, the result of the right choice study was that the median progression-free survival for chemotherapy as compared to ribociclib plus chemotherapy, chemotherapy median progression-free survival was 12 months, ribociclib plus endocrine therapy, 24 months. So, these CDK4/6 inhibitors ribociclib can work for patients in visceral crisis, and it can work, and give us a sustained benefit, which I think is important. And patients with these higher disease burdens, younger patients, don’t necessarily need chemotherapy in first-line, we can still use endocrine therapy.

They did look at time-to-response and there was a slightly faster time-to-response with chemotherapy, but in my opinion, the difference in time-to-response wasn’t a dramatic enough difference that it would justify chemotherapy over endocrine therapy given that magnitude of benefit in median progression-free survival. Overall, I think that, that was another win for ribociclib and CDK4/6 inhibitors, and I was excited to see that data presented to strengthen the landscape of CDK4/6 inhibitors in our treatment of hormone receptor-positive metastatic breast cancer.

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Disclosures

Dr Graff reports stock and other ownership interests in HCA Healthcare.

Dr Graff reports honoraria from The Academy for Healthcare Learning, Pfizer, DAVA Oncology, MJH Life Sciences, WebMD/Medscape, IntegrityCE, MedPage Today, MedIQ, Medical Educator Consortium.

Dr Graff reports consulting or advisory role for Novartis, Pfizer, Novartis, AstraZeneca, Genentech, Lilly, Daiichi Sankyo/Astra Zeneca, Gilead Sciences, Seagen.

Dr Graff reports research funding from Boehringer Ingelheim, Lilly, Genentech, Immunomedics, Novartis, Celldex, Dana Farber Cancer Hospital, TapImmune Inc., Merus NV, Odonate Therapeutics, Innocrin Pharma, GRAIL, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eisai, Roche, H3 Biomedicine, Merck, Foundation Medicine, Seattle Genetics, Taiho Pharmaceutical, Sermonix Pharmaceuticals, Polyphor.

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