357P - Bridging the gap between real-world studies (RWSs) and randomized controlled trials (RCTs) of 1st-line palbociclib+aromatase inhibitors (P+AI) in hormone receptor-positive (HR+)/HER2-negative(-) metastatic breast cancer (mBC)

Background

RCTs remain the gold standard to assess the efficacy of a treatment seeking regulatory approval. However, RWSs provide insights into patients (pts)’ outcomes in routine clinical practice. We assessed the real-world (RW) efficacy of 1^st-line P+AI and compared it to RCTs’ results.

Methods

A systematic review was performed to identify RWSs published from 2019 to 2023 including pts with HR+/HER2- mBC treated with 1^st-line P+AI, with available median progression-free survival (mPFS) and/or overall survival (mOS). A meta-analysis was performed to estimate the pooled mPFS/OS using the median of the medians (MM) and weighted median of medians (WM). The RW estimates were deemed comparable to PALOMA1/2 RCTs' mPFS/OS, if MMPFS/OS or WMPFS/OS were in RCTs' mPFS/OS 95% confidence intervals (CI). Similar criteria applied to pooled hazard ratios (HR) of PFS/OS for P+AI vs. AI in visceral/non-visceral subgroups.

Results

Among 8 included RWSs (n=4624 pts) a MMPFS of 22.5 months (95%CI: 19.5-31.8) and WMPFS of 20.0 (95%CI: 19.3-31.8) were observed with 1^st-line P+AI. The MMPFS was comparable to those of PALOMA1 (20.2, 95%CI: 13.8-27.5) and PALOMA2 (27.6 months, 95%CI: 22.4-30.3). The WMPFS was inferior to that of PALOMA2. A RW MMOS of 51.2 months (95%CI: 49.1-53.3) and WMOS of 49.1 (95%CI: 49.1-53.3) were observed, outperforming the PALOMA1 mOS of 37.5 months (95%CI: 37.5-47.8) and being comparable to PALOMA2 mOS of 53.8 (95%CI: 49.8-59.2). P+AI vs. AI in RW in visceral disease had superior PFS (HR: 0.56, 95%CI: 0.46-0.68) and OS (HR: 0.61, 95%CI: 0.49-0.77), similarly to the PALOMA2 PFS (HR: 0.62, 95%CI: 0.47-0.81) and better than PALOMA1 (HR: 1.13, 95%CI: 0.68-1.88) and PALOMA2 (HR: 0.86, 95%CI: 0.65-1.13) OS. In RW non-visceral disease, P+AI vs. AI had lower PFS benefit (HR: 0.76, 95%CI: 0.65-0.88) than PALOMA2 (HR: 0.50, 95%CI: 0.37-0.67). RW OS (HR: 0.82, 95%CI: 0.69-0.99) was similar than that of PALOMA2 (HR: 0.98, 95%CI: 0.74-1.31).

Conclusions

Our findings add to the understanding of the generalisability of RCTs results to RW and confirm the benefit of palbociclib+AI vs. AI alone.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

F. Schettini: Financial Interests, Personal, Invited Speaker: Novartis, Gilead, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Other, Travel expenses: Novartis, Gilead, Daiichi Sankyo. B. Conte: Financial Interests, Personal, Invited Speaker: Veracyte; Financial Interests, Personal, Other, Educational events: Medsite, Novartis. C. Criscitiello: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Eli-Lilly, Roche, Gilead; Financial Interests, Personal, Advisory Board: MSD, Seagen, AstraZeneca, Daiichi Sankyo. M. Giuliano: Financial Interests, Personal, Speaker, Consultant, Advisor: Lilly, Celgene, Novartis, Pfizer, AstraZeneca, Daiichi Sankyo, MSD; Financial Interests, Personal, Other, honoraria: Lilly, Celgene, Novartis, Pfizer, Istituto Gentili, Eisai Europe Ltd, Roche, AstraZeneca, Daiichi Sankyo, MSD, Gilead; Financial Interests, Personal, Other, Travel expenses: Novartis, Pfizer, Roche. M. Lambertini: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Menarini, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Takeda, Sandoz, Ipsen, Libbs, Knight, Daiichi Sankyo, Lilly, Pfizer, Novartis, Roche, AstraZeneca, Menarini, Gilead; Financial Interests, Personal, Other, Travel grant to attend ASCO 2022: Gilead; Financial Interests, Personal, Other, Travel grant to attend ASCO 2023 and ASCO 2024: Daiichi Sankyo; Financial Interests, Personal, Other, Travel grant to attend SABCS 2023: Roche; Financial Interests, Institutional, Coordinating PI, 2-year research grant paid to my Institution: Gilead; Non-Financial Interests, Leadership Role, Chair of the ESMO Young Oncologists Committee from 01/2023 to 12/2024: ESMO; Non-Financial Interests, Member of Board of Directors, Member of the national council of the Italian Association of Medical Oncology (AIOM): AIOM. R. Sanchez Bayona: Financial Interests, Personal, Invited Speaker: Novartis, AstraZeneca, MSD, Lilly, GSK, Clovis, Seagen, Pfizer, Roche, Gilead ; Financial Interests, Personal, Advisory Board: Novartis, Lilly, GSK, Seagen, Roche; Non-Financial Interests, Personal, Member: ESMO Young Oncologists Committee, Spanish Society of Medical Oncology. T. Pascual: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Veracyte, Argenetics. P. Vigneri: Financial Interests, Personal, Other, Honoraria: AstraZeneca, BMS, Celgene, Ely-Lilly, GSK, Novartis, Pfizer, Teva. G. Arpino: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, AstraZeneca, Novartis, Lilly, MSD, Pfizer; Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca; Financial Interests, Personal, Other, honoraria: Novartis, Lilly, MSD, Pfizer; Financial Interests, Personal, Advisory Board, Travel expenses: Roche, AstraZeneca, Novartis, Lilly, MSD, Pfizer. L. Del Mastro: Financial Interests, Personal, Other, reports grants or contracts: Ely-Lilly, Novartis, Roche, Daiichi Sankyo, Seagen; Financial Interests, Personal, Other, honoraria: Roche, Novartis, Pfizer, Eli-Lilly, AstraZeneca, MSD, Seagen, Gilead, Pierre Fabre, Eisai, Exact Sciences, Ipsen; Financial Interests, Personal, Other, Travel expenses: Roche, Pfizer, Eisai; Financial Interests, Personal, Advisory Board: Novartis, Roche, Eli-Lilly, Pfizer, Daiichi Sankyo, Exact Sciences, Gilead, Pierre Fabre, Eisai, AstraZeneca. M. Cristofanilli: Financial Interests, Personal, Other: Novartis, Menarini, Eli-Lilly, Sermonix, G1 Therapeutics, Foundation Medicine, AstraZeneca, Pfizer, Foundation Medicine, Pfizer; Financial Interests, Personal, Other, Travel Expenses: Foundation Medicine; Financial Interests, Personal, Advisory Board: Merck, AstraZenecaa; Financial Interests, Personal, Research Funding: Pfizer, Menarini, Eli-Lilly, G1 Therapeutics. H.S. Rugo: Financial Interests, Personal, Advisory Board, Consultancy/advisory support: NAPO; Financial Interests, Personal, Invited Speaker, Honoraria: Mylan/Viatris, Chugai; Financial Interests, Personal, Advisory Board, Advisory/Consultancy: PUMA, Sanofi; Financial Interests, Institutional, Local PI: Novartis, Lilly, Pfizer, Daiichi, AstraZeneca, Gilead Sciences, Inc.; Financial Interests, Institutional, Coordinating PI: OBI Pharma, F. Hoffmann-La Roche AG/Genentech, Inc., Merck; Financial Interests, Institutional, Research Grant: Stemline Therapeutics, Ambryx. A. Gennari: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, MSD, Eli-Lilly, Pierre Fabre, Eisai, Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Eisai, Novartis, Eli-Lilly, Roche, Teva, Gentili, Pfizer, AstraZeneca, Celgene, Daiichi Sankyo; Financial Interests, Personal, Research Funding: Eisai, Eli-Lilly, Roche. G. Curigliano: Financial Interests, Personal, Other: Merck; Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, Roche, Pfizer, Novartis, Lilly, AstraZeneca, Daichii Sankyo, Merck, Seagen, Ellipsis, Gilead, Menarini; Financial Interests, Personal, Other, honoraria: Lilly, Pfizer, Relay, Gilead; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Travel expenses: Daichii Sankyo. D. Generali: Financial Interests, Personal, Other, Educational events: Novartis, Lilly, Pfizer, Daiichi Sankyo, Roche; Financial Interests, Personal, Research Funding: AstraZeneca, Novartis, LILT. All other authors have declared no conflicts of interest.