In three MONALEESA phase 3 trials, addition of ribociclib to adjuvant endocrine therapy improved overall survival (OS) in post-menopausal patients with locally advanced/metastatic HR-positive/HER2-negative breast cancer. Now, exploratory analyses demonstrate consistent OS benefit in several subgroups of patients.

Addition of the CDK4/6 inhibitor ribociclib to endocrine therapy significantly improves progression-free survival (PFS) and OS in patients with locally advanced/metastatic HR-positive/HER2-negative breast cancer, as was shown in the phase 3 MONALEESA-2, -3, and -7 trials [1-3]. Now, results were presented of 2 retrospective, exploratory analyses of the OS in subgroups of patients based on data from these trials. First, Dr. Lisa Carey (University of North Carolina, NC, USA) presented results of the association of intrinsic subtypes with OS using tumor samples pooled from all 3 trials [4]. The intrinsic subtyping was based on the gene expression profile of the tumor samples. Of 997 tumour samples that were analysed, 54.4% (n=544) appeared to be Luminal A-type, 27.9% (n=276) Luminal B-type, 14.7% (n=147) HER2-enhanced, and 3.0% (n=30) basal-like. OS data were consistent in the intention-to-treat population (n=2,066) and the biomarker population (n=997). Intrinsic subtype was prognostic for OS both with or without palbociclib: Luminal A>Luminal B>HER-enhanced>basal-like. In all subtypes but basal-like, palbociclib improved OS: HR 0.75, HR 0.69, HR 0.60, and HR 1.89, respectively. “These pooled data show that ribociclib has consistent benefit in Luminal A, Luminal B, and HER-enhanced tumor types. Patients with basal-like tumors seem not to benefit from palbociclib; however, due to the small sample size these results should be interpreted with caution,” summarised Dr. Carey. The second exploratory analysis evaluated the association between OS and location of metastases, number of metastatic sites, and prior therapy of patients in the MONALEESA-2 trial (n=668). Dr. Joyce O’Shaughnessy (Texas Oncology-Baylor University Medical Center, TX, USA) presented the results. OS benefit of ribociclib in patients with or without bone-only metastases appeared to be consistent with that in the intention-to-treat population, as presented at ESMO 2021 [1]. At 5 and 6 years of follow-up, OS benefit of ribociclib was seen both in patients with or without liver metastases. Similarly, OS benefit of ribociclib was observed at 5 and 6 years of follow-up with liver or lung metastases. In addition, OSbenefit of ribociclib was independent of the number of metastatic sites and independent of prior (neo)adjuvant chemotherapy or endocrine therapy. “So, this exploratory subgroup analysis demonstrated benefit of ribociclib independent of metastatic side, metastatic number, and/or prior therapy,” concluded Dr. O’Shaughnessy.

  1. Hortobagyi GN, et al. Ann Oncol 2021;32(suppl_5):S1283-S1346
  2. Slamon DJ, et al. N Engl J Med 2020;38:514-524.
  3. Im S-H, et al. N Engl J Med 2019;381:307-316.
  4. Carey LA, et al. Correlative analysis of overall survival by intrinsic subtype across the MONALEESA-2, -3, and -7 studies of ribociclib + endocrine therapy in patients with HR+/HER2− advanced breast cancer. SABCS 2021 Virtual Meeting, abstract GS2-00.
  5. O’Shaughnessy J, 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 advanced HR+/HER2− breast cancer. SABCS 2021 Virtual Meeting, abstract GS2-01.

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