Background

In 3 Phase III trials, RIB (cyclin-dependent kinase 4/6 inhibitor) + various ET partners demonstrated longer progression-free survival (PFS) vs placebo (PBO) + ET in patients (pts) with HR+/HER2– ABC. Using pooled trial data from the MONALEESA–2 (ML-2; all patients), ML-3 (ET-naïve subgroup only), and ML-7 (NSAI subgroup only) trials, we further evaluate efficacy in ET-naive pts here.

Methods

ML-2 and ML-3 enrolled ET-naive postmenopausal pts with ABC to receive PBO or RIB + study-designated ET, letrozole (ML-2) or fulvestrant (ML-3). In ML-7, ET-naive premenopausal pts with ≤1 line of chemotherapy for ABC received RIB or PBO + goserelin + nonsteroidal aromatase inhibitor or tamoxifen. The primary endpoint was locally assessed PFS. Secondary endpoints included clinical benefit rate (CBR) and overall response rate (ORR).

Results

Data were pooled from 1530 pts (including 34% with de novo metastatic disease) treated with RIB + ET (n = 820) or PBO + ET (n = 710). Median follow-up time for PFS was 15.1 (ML-2), 16.5 (ML-3), and 13.0 (ML-7) months. Addition of RIB to ET prolonged PFS vs PBO (median, 25.3 vs 15.6 months; HR, 0.57 [95% CI, 0.49-0.66]). The PFS benefit of RIB + ET over PBO + ET was observed in most pt subgroups, including those defined by age, race, baseline ECOG performance status, presence of visceral or bone metastases, de novo metastatic disease, and prior chemotherapy. ORR and CBR were both improved in the RIB arm vs the PBO arm, and the estimated probabilities of tumor response for RIB vs PBO were 16.0% vs 10.0% at 2 months, 35.2% vs 22.6% at 6 months, and 42.3% vs 28.8% at 12 months (Table).

Conclusions

The addition of RIB to several ET partners consistently demonstrated longer PFS and higher response rates vs PBO + ET in this pooled population. This very large data set (> 1500 pts) supports RIB-based ET as an option for a diverse population of pre- and postmenopausal pts with ET-naive HR+/HER2– ABC.

Editorial acknowledgement

MediTech Media, funded by Novartis.

Clinical trial identification

MONALEESA-2 (NCT01958021), MONALEESA-3 (NCT02422615), MONALEESA-7 (NCT02278120).

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

D. Tripathy: Grants, personal fees: Novartis; Pfizer during the conduct of the study; Personal fees: Nektar Therapeutics, CellMax Life, Sellas Life Sciences, Polyphor Ltd, GlaxoSmithKline, Genomic Health, outside the submitted work. G.N. Hortobagyi: The work under consideration for publication - Novartis: Grant and personal fees; Relevant financial activities outside the submitted work - Consulting: Lilly, Pfizer. S-A. Im: Relevant financial activities outside the submitted work: AstraZeneca - Grant Spectrum, Novartis, Roche/Genetech - Advisory board member. S. Chia: Honorarium for advisory boards: Novartis, Hoffmann LaRoche, Pfizer, AstraZeneca, Genomic Health; My institution has participated in research studies: Novartis, Hoffmann La Roche, Pfizer, AstraZeneca, Genomic Health, Genentech, Merck, BMS. S.A. Hurvitz: Grants: Ambryx, Amgen, Bayer, OBI Pharma, Bimarin, Cascadian, Daiichi Sankyo, Dignitana, Genentech, Gsk, Lilly, Macrogenics, Medivation, Merrimack, Novartis, OBI Pharma, Pfizer, Pieris, Puma, Roche, Seattle Genetics. A. Ridolfi: Employee: Novartis Pharmaceuticals Corporation. All other authors have declared no conflicts of interest.

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