Consistent overall survival benefit of ribociclib in advanced breast cancer

In 3 trials, addition of ribociclib to endocrine therapy improved overall survival in postmenopausal patients with locally advanced/metastatic hormone receptor (HR)-positive/HER2-negative breast cancer. Exploratory analyses now demonstrated consistent overall survival benefit in several subgroups of patients.

Addition of the CDK4/6 inhibitor ribociclib to endocrine therapy significantly improves progression-free and overall survival 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 (NCT01958021, NCT02422615, NCT02278120) [1–3]. Based on data from these 3 phase 3 trials, 2 retrospective, exploratory analyses of the overall survival were done in subgroups of patients.

Prof. Lisa Carey (University of North Carolina School of Medicine, NC, USA) presented results of the association of intrinsic subtypes with overall survival using tumour samples pooled from all 3 trials [4]. The intrinsic subtyping was based on the gene expression profile of the tumour samples. Of 997 tumour samples that were analysed, 54.4% appeared to be Luminal A-type, 27.9% Luminal B-type, 14.7% HER2-enhanced, and 3.0% basal-like. Overall survival data were consistent in the intent-to-treat population (n=2,066) and the biomarker population (n=997). Intrinsic subtype was prognostic for overall survival, both with or without ribociclib: Luminal A>Luminal B>HER-enhanced>basal-like. In all subtypes but basal-like, ribociclib improved overall survival: HR 0.75 and P=0.021, HR 0.69 and P=0.023, HR 0.60 and P=0.018, and HR 1.89 and P=0.148, respectively.

“These pooled data show that ribociclib has consistent benefit in Luminal A, Luminal B, and HER-enhanced tumour types. Patients with basal-like tumours seem not to benefit from ribociclib. However, due to the small sample size these results should be interpreted with caution,” summarised Prof. Carey.

The second exploratory analysis evaluated the association between overall survival and location of metastases, number of metastatic sites, and prior therapy of patients in the MONALEESA-2 trial (n=668). Dr Joyce O’Shaughnessy (Baylor University Medical Center, TX, USA) presented the results.

Overall survival benefit of ribociclib in patients with or without bone-only metastases appeared to be consistent with that in the intention-to-treat population [5]. At 5- and 6-years follow-up, overall survival benefit of ribociclib was seen both in patients with and without liver metastases. Similarly, overall survival benefit of ribociclib was observed at 5- and 6-years follow-up with liver or lung metastases. In addition, overall survival benefit 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(suppl5):S1283–S1346.
2. Slamon DJ, et al. N Engl J Med 2020;38:514–524.
3. Im S-A, 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. GS2-00, SABCS 2021 Virtual Meeting, 7–10 December.
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. GS2-01, SABCS 2021 Virtual Meeting, 7–10 December.

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Posted on 31 January 2022