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

Abstract

BackgroundPatients 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 methodsPatients 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.ResultsOf 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).ConclusionsHRQoL 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 numberNCT02184195.

<p>Cost-Effectiveness Analysis of Maintenance Olaparib in Patients with Metastatic Pancreatic Cancer and a Germline BRCA1/2 Mutation Based on the POLO Trial</p>

“…There is no health utility value of pancreatic cancer for Chinese patients, and the POLO trial did not report health utility values of the PFS and PD states. Maintenance olaparib did not compromise the quality of life compared with placebo in the POLO trial, 11 , 14 so we assumed the utility scores to be similar between the two groups in the same health state and used the health utility value of non-Asian patients from published studies in our model. In addition, the POLO trial did not provide enough detailed information on sequential therapy, and we assumed that the costs for AEs and testing in the PD state were the same and did not include these costs when calculating the cost of the PD state.…”

“…The survival curve simulation results are presented in Figure 2 . We used the formula S(t)=P(T≥t)=exp(-λt γ ) to estimate the survival probability at time t and the formula P(t)=1-exp[(λ(t-1) γ -λt γ ] to estimate the transition probability at a given cycle t. There was no significant difference between the olaparib group and the placebo in terms of health-related quality of life in the POLO trial, 14 and we assumed that the health utility values were the same in both groups. Health utility values were adopted from a recently published study.…”

Adjuvant Pancreatic Cancer Management: Towards New Perspectives in 2021

“…An interim analysis of OS with 46% mature data, showed no difference between the olaparib and placebo groups (median OS: 18.9 months vs. 18.1 months; HR for death: 0.91; 95% CI 0.56–1.46; p = 0.68). Quality of life was not impaired with olaparib [ 81 ]. It would be interesting to test the value of olaparib in patients with tumors containing somatic mutations as there seems to be a possible difference between somatic and germinal BRCA mutation status in relation to response ton parp-inhibitors [ 82 ].…”

BRCA in Gastrointestinal Cancers: Current Treatments and Future Perspectives

“…No difference in terms of median OS was observed between the two groups (18.9 vs. 18.1 months in the olaparib arm and placebo arm, respectively, p = 0.68), but data are still immature for this outcome since they derive from a planned interim analysis at data maturity of 46% [ 38 ]. Health-related quality of life (HRQoL) was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo, an important result for patients particularly when considering the cumulative toxicities of standard-of-care chemotherapies [ 39 ]. Of note, 21.7% of patients in the POLO trial progressed on first-line treatment and were ineligible for randomization, consistent with findings reported by Wattenberg et al [ 40 ] in their retrospective real-world cohort study where over 40% of BRCA -defective PC patients did not respond to platinum-based chemotherapy and up to 20% had disease progression as best response even in the first-line setting.…”