Patient-Reported Outcomes in OlympiA: A Phase III, Randomized, Placebo-Controlled Trial of Adjuvant Olaparib in g<i>BRCA1/2</i> Mutations and High-Risk Human Epidermal Growth Factor Receptor 2–Negative Early Breast Cancer
Authors: Patricia A. Ganz, Hanna Bandos, Tanja Španić, Sue Friedman, Volkmar Müller, Sherko Kuemmel, Suzette Delaloge, Etienne Brain, Masakazu Toi, Hideko Yamauchi, Eduardo-M. de Dueñas, Anne Armstrong, Seock-Ah Im, Chuan-gui Song, Hong Zheng, Tomasz Sarosiek, Priyanka Sharma, Cuizhi Geng, Peifen Fu, Kerstin Rhiem, Heike Frauchiger-Heuer, Pauline Wimberger, Daphné t'Kint de Roodenbeke, Ning Liao, Annabel Goodwin, Camille Chakiba-Brugère, Michael Friedlander, Keun Seok Lee, Sylvie Giacchetti, Toshimi Takano, Fernando Henao-Carrasco, Shamsuddin Virani, Frances Valdes-Albini, Susan M. Domchek, Charles Bane, Edward C. McCarron, Monica Mita, Giovanna Rossi, Priya Rastogi, Anitra Fielding, Richard D. Gelber, Elsemieke D. Scheepers, David Cameron, Judy Garber, Charles E. Geyer, Andrew N.J. Tutt
Journal: Journal of Clinical Oncology (2024)

PURPOSE The OlympiA randomized phase III trial compared 1 year of olaparib (OL) or placebo (PL) as adjuvant therapy in patients with germline BRCA1/2, high-risk human epidermal growth factor receptor 2–negative early breast cancer after completing (neo)adjuvant chemotherapy ([N]ACT), surgery, and radiotherapy. The patient-reported outcome primary hypothesis was that OL-treated patients may experience greater fatigue during treatment. METHODS Data were collected before random assignment, and at 6, 12, 18, and 24 months. The primary end point was fatigue, measured with the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Secondary end points, assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 item, included nausea and vomiting (NV), diarrhea, and multiple functional domains. Scores were compared between treatment groups using mixed model for repeated measures. Two-sided P values &lt;.05 were statistically significant for the primary end point. All secondary end points were descriptive. RESULTS One thousand five hundred and thirty-eight patients (NACT: 746, ACT: 792) contributed to the analysis. Fatigue severity was statistically significantly greater for OL versus PL, but not clinically meaningfully different by prespecified criteria (≥3 points) at 6 months (diff OL v PL: NACT: –1.3 [95% CI, –2.4 to –0.2]; P = .022; ACT: –1.3 [95% CI, –2.3 to –0.2]; P = .017) and 12 months (NACT: –1.6 [95% CI, –2.8 to –0.3]; P = .017; ACT: –1.3 [95% CI, –2.4 to –0.2]; P = .025). There were no significant differences in fatigue severity between treatment groups at 18 and 24 months. NV severity was worse in patients treated with OL compared with PL at 6 months (NACT: 6.0 [95% CI, 4.1 to 8.0]; ACT: 5.3 [95% CI, 3.4 to 7.2]) and 12 months (NACT: 6.4 [95% CI, 4.4 to 8.3]; ACT: 4.5 [95% CI, 2.8 to 6.1]). During treatment, there were some clinically meaningful differences between groups for other symptoms but not for function subscales or global health status. CONCLUSION Treatment-emergent symptoms from OL were limited, generally resolving after treatment ended. OL- and PL-treated patients had similar functional scores, slowly improving during the 24 months after (N)ACT and there was no clinically meaningful persistence of fatigue severity in OL-treated patients.