Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib

Hammel, P.; Kindler, H. L.; Reni, M.; Van Cutsem, E.; Macarulla, T.; Hall, M. J.; Park, J. O.; Hochhauser, D.; Arnold, D.; D. -Y., Oh; Reinacher-Schick, A.; Tortora, G.; Algul, H.; O'Reilly, E. M.; Mcguinness, D.; Cui, K. Y.; Joo, S.; Yoo, H. K.; Patel, N.; Golan, T.; Chantrill, L.; Goldstein, D.; Joubert, W.; Pavlakis, N.; Tognela, A.; Van Cutsem, E.; Van Fraeyenhove, F.; Van Laethem, J. -L.; Peeters, M.; Dhani, N.; Kavan, P.; Lemay, F.; Adenis, A.; Artru, P.; Baba-Hamed, N.; Belletier, C.; Ben Abdelghani, M.; Blanc, J. -F.; Borg, C.; Coriat, R.; Deplanque, G.; Faroux, R.; Follana, P.; Guimbaud, R.; El Hajbi, F.; Hammel, P.; Hautefeuille, V.; Malka, D.; Metges, J. -P.; Tougeron, D.; Walter, T.; Algul, H.; Ettrich, T.; Hacker, U. T.; Hennes, E.; Jacobasch, L.; Kanzler, S.; Pession, U.; Reinacher-Schick, A.; Scholz, C.; Sinn, M.; Stein, A.; Strassburg, C.; Vogel, A.; Ben-Shahar, M.; Brenner, R.; Epelbaum, R.; Geva, R.; Gluzman, A.; Golan, T.; Idelevich, E.; Kolin, M.; Semenisty, V.; Shai, A.; Stemmer, S.; Yarom, N.; Celio, L.; Conte, P.; Garufi, C.; Gianni, L.; Leonardi, F.; Maiello, E.; Di Marco, M.; Milella, M.; Pinto, C.; Santini, D.; Scartozzi, M.; Tortora, G.; Vaccaro, V.; Vasile, E.; Kim, J. -W.; Kim, J. -W.; D. -Y., Oh; Oh Park, J.; Wilmink, H.; Gallego, R. A.; Ogalla, G. D.; Velasco, A. G.; Cabanas, E. G.; Gomez Martin, C.; Ponce, C. G.; Saez, B. L.; Lopez, R.; Macarulla, T.; Martin, A. M.; Pazo, R.; Pijaume, C. P.; Rodriguez, J.; Yaya-Tur, R.; Arora, A.; Anthoney, D. A.; Jeffrey Evans, T. R.; Harrison, M.; Hochhauser, D.; Palmer, D.; Sarker, D.; Starling, N.; Valle, J.; Wall, L.; Agajanian, R.; Bearden, J.; Bekaii-Saab, T.; Carter, C.; Cohen, D.; Distefano, A.; Dragovich, T.; Ejadi, S.; Ford, J.; Grabelsky, S.; Hall, M.; Hochster, H.; Hosein, P.; Javle, M.; Kindler, H.; Lacy, J.; Laheru, D.; Leong, S.; Lowery, M.; Marsh, R.; Noonan, A.; Oberstein, P.; Ocean, A.; O'Reilly, E.; Ryan, D.; Seery, T.; Subramaniam, S.; Van Echo, D.; Wang-Gillam, A.; Weekes, C.; Welch, S.

doi:10.1093/annonc/mdz406

Background: Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. Patients and methods: Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. Results: Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [-2.47; 95% confidence interval (CI) -7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI -8.75, -0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63). Conclusions: HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. ClincalTrials.gov number: NCT02184195.