Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: Postmenopausal patients given first-line ribociclib plus fulvestrant for hormone receptor-positive, HER2-negative advanced breast cancer continue to have a significant overall survival (OS) advantage over those given placebo plus fulvestrant after more than 70 months of follow-up, exploratory analyses show.
The MONALEESA-3 trial update was given to attendees of the ESMO Breast Cancer 2022 in Berlin, Germany, by Patrick Neven, from University Hospitals Leuven in Belgium. He said that the treatment combination had “demonstrated the longest median OS observed for a first-line population in a phase III trial setting in advanced breast cancer as of today.”
The full trial population included postmenopausal women and men who were treatment-naïve – defined as a de novo diagnosis or a treatment interval of at least 12 months for earlier-stage disease – or who had resistance to one line of endocrine therapy.
The investigator reminded delegates that the final protocol-specified analysis of MONALEESA-3 had demonstrated a significant OS benefit with use of the CDK4/6 inhibitor alongside the selective oestrogen receptor degrader at 40 months, as had an exploratory analysis after 56 months, but at these timepoints the median OS had not been reached in the first-line treatment subgroup.
After a median of 70.8 months of follow-up (minimum 67.3 months), the current exploratory analysis showed a 15.8-month gain in median OS for patients given ribociclib plus fulvestrant in the first line compared with placebo plus fulvestrant (67.6 vs 51.8 months), with a hazard ratio (HR) for death of 0.67. At 5 years, 56.5% of the CDK4/6 inhibitor arm were alive compared with 42.1% of controls.
Most patients in both the ribociclib and placebo arms had discontinued their study treatment at the time of analysis (83.5 vs 91.4%), with the majority receiving antineoplastic therapy (81.8 vs 89.7%) consisting of chemotherapy and/or hormone therapy. There were lower rates of subsequent CDK4/6 inhibitor use in the ribociclib than the control arm (16.7 vs 35.0%), noted the presenter.
Patrick Neven also reported that first-line ribociclib plus fulvestrant offered “consistent” and significant improvements over placebo plus fulvestrant for the secondary endpoints of time to second progression or death after beginning subsequent therapy (median 50.7 vs 34.6 months, HR=0.64) and time to the beginning of first chemotherapy or death (49.2 vs 29.0 months, HR=0.62), as well as overall time to first use of chemotherapy (HR=0.57).
The presenter added that there were no new safety signals with the extended follow-up, and rates of adverse events were “generally consistent with prior analyses”. The rates of adverse events of special interest were also “stable” in both the ribociclib and placebo treatment arms, including for any-grade neutropenia (73.8 vs 4.7%), leukopenia (32.5 vs 1.6%) and hepatobiliary toxicity (26.6 vs 17.2%), he continued.
“These results stress the importance of combining these agents with endocrine treatment in advanced breast cancer”, Patrick Neven concluded.
Discussing the presentation at the session, Mafalda Oliveira, from Vall d’Hebron University Hospital in Barcelona, Spain, agreed with the investigator that the MONALEESA-3 findings were “impressive”.
She wondered whether the de novo patients in the study had a better outcome than those who had previously been treated for breast cancer at an earlier stage, and observed that “only 35% of the patients in the placebo group received subsequent CDK4/6 inhibitor [therapy] and perhaps this does not reflect the current treatment landscape in this context.”
The discussant concluded that she now looks forward to seeing the OS results for the phase III PALOMA-2 study of first-line palbociclib plus letrozole later this year, and is awaiting the mature results for the phase III MONARCH-3 trial of first-line abemaciclib plus letrozole.
Reference
Cecala A, Neven P, Fasching PA, et al. Updated overall survival (OS) results from the first-line (1L) population in the phase III MONALEESA-3 trial of postmenopausal patients (pts) with HR+/HER2? Advanced breast cancer (ABC) treated with ribociclib (RIB) + fulvestrant (FUL). Ann Oncol 2022;33(suppl_3):S194–S223. doi:10.1016/annonc/annonc894
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