The phase 3 MONALEESA-3 trial (NCT02422615) previously demonstrated a statistically significant improvement in progression-free survival (PFS) and OS with ribociclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, plus fulvestrant compared with placebo plus fulvestrant as first-line or second-line treatment in postmenopausal patient with HR-positive, HER2-negative, advanced breast cancer [1,2].

In the trial, patients (n=726) were randomised 2:1 to receive ribociclib plus fulvestrant or placebo plus fulvestrant in first-line and second-line settings. At the cut-off date for the pre-planned, final OS analysis, the median OS in the ribociclib arm was not yet reached versus 40.0 months in de placebo arm (HR 0.72; 95% CI 0.57-0.92; P =0.00455).

Following the unblinding of the study, patients still on study treatment in the placebo arm were allowed to cross over to the ribociclib arm. To further characterise the long-term survival benefits of ribociclib versus placebo, an exploratory analysis was performed after a total median follow-up of 56.3 months. Additional post-progression endpoints such as second PFS, time to chemotherapy, and chemotherapy-free survival were also evaluated. Prof. Dennis Slamon (David Geffen School of Medicine at UCLA, CA, USA) presented the outcomes of this exploratory analysis [3].

At the data cut-off, the median follow-up was 56.3 months and 68 (14.0%) and 21 (8.7%) patients were still on treatment in the ribociclib and placebo arms, respectively. With this extended follow-up, ribociclib plus fulvestrant continued to demonstrate an OS benefit versus placebo plus fulvestrant, although 30% of patients in the placebo arm crossed over to a CDK4/6 inhibitor: median OS was 53.7 months versus 41.5 months, respectively (HR 0.73; 95% CI 0.59-0.90). Ribociclib plus fulvestrant had prolonged OS versus placebo plus fulvestrant both in in the first-line (median not reached vs 51.8 months [HR 0.64; 95% CI 0.46-0.88]) and second-line subgroups (median 39.7 versus 33.7 months [HR 0.78; 95% CI 0.59-1.04]). Second PFS, time to chemotherapy, and chemotherapy-free survival for the ITT population also favoured ribociclib over placebo: HR 0.69 (95% CI 0.57-0.84), HR 0.70 (95% CI 0.57-0.88), and HR 0.69 (95% CI 0.57-0.83), respectively. Safety data was consistent with that previously reported in earlier analyses of MONALEESA-3. No new safety signals were observed.

“The previously demonstrated robust and clinically meaningful OS benefit with ribociclib plus fulvestrant compared with placebo plus fulvestrant was maintained after almost 5 years of follow-up,” concluded Prof. Slamon.

1. Slamon DJ, et al. J Clin Oncol. 2018;36:2465-2472.

2. Slamon DJ, et al. N Engl J Med. 2020;382:514-524.

3. Slamon DJ, et al. Updated overall survival (OS) results from the phase III MONALEESA-3 trial of postmenopausal patients (pts) with HR+/HER2- advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB). ASCO 2021 Virtual Meeting, abstract 1001.

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Fuente: Medicom Medical Publishers