Population-adjusted indirect treatment comparison of the SOLO1 and PAOLA-1/ENGOT-ov25 trials evaluating maintenance olaparib or bevacizumab or the combination of both in newly diagnosed, advanced BRCA-mutated ovarian cancer.

Background: In the absence of randomised head-to-head trials, we conducted a population-adjusted indirect treatment comparison (PA-ITC) of phase III trial data to evaluate the relative efficacy and safety of maintenance olaparib and bevacizumab alone and in combination in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation (BRCAm).
Methods: An unanchored PA-ITC was performed on investigator-assessed progression-free survival (PFS) data. Individual patient data from SOLO1 (olaparib versus placebo) and from BRCA-mutated patients in PAOLA-1/ENGOT-ov25 (olaparib plus bevacizumab versus placebo plus bevacizumab) were pooled. Each arm of PAOLA-1 was weighted so that key baseline patient characteristics were similar to the SOLO1 cohort. Analyses were performed in patients with complete baseline data. Weighted Cox regression analysis was used to estimate the comparative efficacy of different maintenance therapy strategies, supplemented by weighted Kaplan-Meier analyses.
Results: Data from SOLO1 patients (olaparib, n = 254; placebo, n = 126) were compared with data from BRCA-mutated PAOLA-1 patients (olaparib plus bevacizumab, n = 151; placebo plus bevacizumab, n = 71). Adding bevacizumab to olaparib was associated with a numerical improvement in PFS compared with olaparib alone (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.45-1.09). Statistically significant improvements in PFS were seen with olaparib alone versus placebo plus bevacizumab (HR 0.48; 95% CI 0.30-0.75), olaparib plus bevacizumab versus placebo (0.23; 0.14-0.34), and placebo plus bevacizumab versus placebo (0.65; 0.43-0.95).
Conclusions: Results of this hypothesis-generating PA-ITC analysis support the use of maintenance olaparib alone or with bevacizumab in patients with newly diagnosed, advanced ovarian cancer and a BRCAm.
Competing Interests: Conflict of interest statement Ignace Vergote: reports consulting fees, paid to his institution, from Advaxis, Eisai, MSD Belgium, F. Hoffman-La Roche, Millennium Pharmaceuticals, Oncoinvent and Sotio; consulting fees, paid to his institution, and travel support from Roche, Genmab, PharmaMar, Clovis Oncology, AstraZeneca, Tesaro and Immunogen; grant support, paid to his institution, from Amgen, Stichting tegen Kanker and Roche; research support from Oncoinvent and Genmab; and travel support from Takeda Oncology. Isabelle Ray-Coquard: reports consulting fees, grant and travel support from AstraZeneca and Roche, consulting fees and travel support from GlaxoSmithKline, consulting fees from Clovis Oncology, PharmaMar, Mersana Therapeutics, Deciphera Pharmaceutical, Amgen and Chugai Pharmaceutical, grant support from Bristol Myers Squibb, and consulting fees and grant support from Merck Sharp & Dohme. Daniel M. Anderson: reports nothing to disclose. Guilherme Cantuaria: reports nothing to disclose. Nicoletta Colombo: reports personal fees from AstraZeneca, MSD, Roche, Tesaro, GSK, Clovis Oncology, PharmaMar, Pfizer, Amgen, Novartis, Biocad and Immunogen. Claire Garnier-Tixidre: reports personal fees from Roche, AstraZeneca, Pfizer and Lilly and non-financial support from MSD and Pfizer. Lucy Gilbert: reports consulting fees from GSK, Merck, Eisai, Astra Zeneca and Alkermes, and grant support from Alkermes, Immunogen, AstraZeneca, Esperas Pharma Inc, Merck Sharp & Dohme, Marsan Therapeutics, Roche, Tesaro, Pfizer and Karyopharm Therapeutics. Philipp Harter: reports consulting fees and grant support from AstraZeneca, Roche, Tesaro, and GlaxoSmithKline, consulting fees from Sotio, Zai Lab, Merck Sharp & Dohme, Clovis Oncology and Immunogen, and grant support from Boehringer Ingelheim, Medac, Genmab, the European Union, Deutsche Krebshilfe and Deutsche Forschungsgemeinschaft. Robert Hettle: reports full-time employment with AstraZeneca and AstraZeneca stock ownership. Domenica Lorusso: reports consultancy fees from Amgen and PharmaMar; advisory board fees and speaker fees from AstraZeneca; advisory board fees, speaker fees and grant support for academic trials (institutional) from GSK and MSD; speaker fees, grants (institutional) and financial support for trial co-ordination (institutional) from Clovis Oncology; and non-financial support from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Roche and the Gynecological Cancer InterGroup. Johanna Mäenpää: reports consulting fees from AstraZeneca, Clovis, MSD and Orion Pharma; and consulting fees and travel support from Roche and Tesaro/GSK. Christian Marth: reports personal fees from AstraZeneca, MSD, Roche, Tesaro, GSK, Clovis Oncology, PharmaMar, Pfizer, Amgen, Novartis, Seagen and Biocad. Koji Matsumoto: reports institutional fees for clinical trials from AbbVie, AstraZeneca, Chugai, Eisai, Lilly, ICON, MSD and ONO and personal fees from AbbVie, AstraZeneca, Chugai, Kyowa-Kirin, Lilly and Pfizer. Mario Ouwens: reports full-time employment with AstraZeneca and AstraZeneca stock ownership. Andrés Poveda: reports grants and personal fees from AstraZeneca and personal fees from PharmaMar, AstraZeneca, Roche, Clovis Oncology and Tesaro. Francesco Raspagliesi: reports grants and travel support from Astra Zeneca, MSD, Clovis, Pharmamar, Roche and GSK. Kirsty Rhodes: reports full-time employment with AstraZeneca and AstraZeneca stock ownership. María Jesus Rubio Pérez: reports nothing to disclose. Ronnie Shapira-Frommer: reports advisory board fees from MSD, VBL Therapeutics, Eisai and Clovis Oncology, research grant from MSD; and speaker honoraria from MSD, BMS, Novartis, Roche, Medison, Neopharm and AstraZeneca. Ayumi Shikama: reports nothing to disclose. Magdalena Sikorska: reports nothing to disclose. Kathleen Moore: reports personal fees from AstraZeneca, AbbVie, Aravive, Eisai, GSK/Tesaro, Genentech/Roche, Immunogen, Merck, Myriad, Mersana, VBL Therapeutics, Vavotar and Tarveda, outside the submitted work. Paul DiSilvestro: reports personal fees from AstraZeneca.
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