Long-Term Results with Everolimus in Advanced Hormone Receptor Positive Breast Cancer in a Multicenter National Real-World Observational Study

Hélène François-Martin, Audrey Lardy-Cléaud, Barbara Pistilli, Christelle Levy, Véronique Diéras, Jean-Sébastien Frenel, Séverine Guiu, Marie-Ange Mouret-Reynier, Audrey Mailliez, Jean-Christophe Eymard, Thierry Petit, Mony Ung, Isabelle Desmoulins, Paule Augereau, Thomas Bachelot, Lionel Uwer, Marc Debled, Jean-Marc Ferrero, Florian Clatot, Anthony Goncalves, Michael Chevrot, Sylvie Chabaud, Paul Cottu, Hélène François-Martin, Audrey Lardy-Cléaud, Barbara Pistilli, Christelle Levy, Véronique Diéras, Jean-Sébastien Frenel, Séverine Guiu, Marie-Ange Mouret-Reynier, Audrey Mailliez, Jean-Christophe Eymard, Thierry Petit, Mony Ung, Isabelle Desmoulins, Paule Augereau, Thomas Bachelot, Lionel Uwer, Marc Debled, Jean-Marc Ferrero, Florian Clatot, Anthony Goncalves, Michael Chevrot, Sylvie Chabaud, Paul Cottu

Abstract

Everolimus is the first oral targeted therapy widely used in advanced HR+/HER2- breast cancer. We sought to evaluate the impact of everolimus-based therapy on overall survival in the ESME-MBC database, a national metastatic breast cancer cohort that collects retrospective data using clinical trial-like methodology including quality assessments. We compared 1693 patients having received everolimus to 5928 patients not exposed to everolimus in the same period. Overall survival was evaluated according to treatment line, and a propensity score with the inverse probability of treatment weighting method was built to adjust for differences between groups. Crude and landmark overall survival analyses were all compatible with a benefit from everolimus-based therapy. Adjusted hazard ratios for overall survival were 0.34 (95% CI: 0.16-0.72, p = 0.0054), 0.34 (95% CI: 0.22-0.52, p < 0.0001), and 0.23 (95% CI: 0.14-0.36, p < 0.0001) for patients treated with everolimus in line 1, 2, and 3 and beyond, respectively. No clinically relevant benefit on progression-free survival was observed. Causes for everolimus discontinuation were progressive disease (56.2%), adverse events (27.7%), and other miscellaneous reasons. Despite the limitations inherent to such retrospective studies, these results suggest that adding everolimus-based therapy to the therapeutic sequences in patients with advanced HR+/HER2- breast cancer may favorably affect overall survival.

Keywords: advanced luminal breast cancer; everolimus; overall survival; real-world data.

Conflict of interest statement

JSF declares consulting fees from Pfizer, Lilly, Novartis, AstraZeneca, Clovis Oncology, GSK, Gilead, Daiichi Sankyo, Seagen, Exact Science; honoraria for lectures from Lilly, Novartis, Gilead, Daiichi Sankyo, Seagen; travel support and meeting attendance from Pfizer, Milly, Novartis, AstraZeneca, Clovis Oncology, GSK, Gilead, Daiichi Sankyo, Seagen. AG declares Institutional research funding from MSD, BMS, Novartis, Boehringer Ingelheim, Roche Genentech, AstraZeneca, Sanofi, and Daiichi Sankyo. PC declares consulting fees and honoraria from Pfizer, Roche, Lilly; Institutional research funding from Novartis, Pfizer; travel support and meeting attendance from Roche, Pfizer, and Daiichi Sankyo. All other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Patient disposition. Patient characteristics at metastatic diagnosis and at the start of each therapeutic line are detailed in Table 1 and in Table 2, Table 3 and Table 4.
Figure 2
Figure 2
Overall survival in the entire population, according to everolimus exposure.
Figure 3
Figure 3
Landmark analysis of overall survival in the entire population, according to minimal follow-up. (A) 6-month landmark OS. (B) 12-month landmark OS.
Figure 4
Figure 4
IPTW-adjusted overall survival, according to line of treatment with everolimus. (A) first line; (B) second line; (C) third line and beyond.

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