Safety of maintenance olaparib in patients with a germline BRCA1 and/or BRCA2 mutation and metastatic pancreatic cancer is consistent irrespective of age. Furthermore, patients aged ≥65 years can derive long-term progression-free survival (PFS) benefit and durable tumour response from the maintenance treatment according to an additional analysis of the POLO trial. Study investigators led by Dr. Hedy Lee Kindler of the University of Chicago in Chicago, US presented the findings at ESMO World Congress on Gastrointestinal Cancer 2020 Virtual (1-4 July).
The authors explained that in the phase III POLO study, treatment with maintenance olaparib provided a statistically significant and clinically meaningful improvement in PFS in comparison to placebo among patients with a germline BRCA1 and/or BRCA2 mutation and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy.
While a subgroup analysis showed consistency of treatment effect across prespecified groups, the hazard ratio in patients aged ≥65 years was 1.02 (95% confidence interval [CI] 0.45-2.60) according to 2019 publication by Golan et al. in The New England Journal of Medicine. To better determine the efficacy and safety of olaparib in patients aged ≥65 years, the study team performed additional analyses by age group.
Following at least 16 weeks of treatment with first-line platinum-based chemotherapy, patients without progression were randomised to maintenance olaparib or placebo until investigator-assessed disease progression or unacceptable toxicity.
The PFS and response were assessed by blinded independent central review using modified RECIST v1.1.
Of 92 patients in olaparib arm, 28 patients (30%) were aged ≥65, versus 13 of 62 patients (21%) in placebo arm.
Fewer older patients had ECOG performance status 0: of those ≥65 years 64% in olaparib arm versus 46% in placebo arm, while among those <65 years 73% versus 65%, respectively.
Median time from diagnosis to randomisation was shorter in patients ≥65 years 6.1 months versus 6.8 months and in those <65 years 7.3 months versus 7.1 months. All patients aged ≥65 were Caucasian (<65 years 84% versus 94%).
There was no difference in median baseline EORTC QLQ-C30 physical functioning score between age groups (≥65 years 87 versus 80; <65 years 87 versus 87; scale 0-100, higher score represents higher functioning).
At the data cut-off of 15 January 2019, 3 of 28 patients (11%) aged ≥65 years versus 7 of 64 patients (11%) aged <65 years had received olaparib for at least 2 years.
At 1 year, 21% of patients in olaparib arm versus 41% of patients in placebo arm aged ≥65 years were progression-free (<65 years: 39% versus 9%), and at 2 years, 21% of patients in olaparib arm versus 0% of patients in placebo arm remained progression-free (<65 years: 23% versus 9%). However, the study team commented that between-group comparisons may be impacted by small subgroups.
In total 4 of 28 patients (14%) aged ≥65 years had a partial response (PR; n=3) or complete response (CR; n=1) to maintenance olaparib versus 3 of 13 patients (23%, all PR) in the placebo arm (<65 years: 14 of 64 patients [22%, 1 CR] versus 3 of 49 patients [6%, all PR]).
Among responders aged ≥65 years, duration of first-line chemotherapy was 3.7-5.6 months and baseline characteristics were consistent with those of younger responders; the complete responder aged ≥65 years had metastatic lung disease and had received 5.6 months of first-line chemotherapy.
At the data cut-off, response duration among older patients was 10.2-32.2 months, and 3 of 4 were ongoing.
In total, 43% of patients treated with olaparib and aged ≥65 years experienced a grade ≥3 adverse event versus 33% of patients in placebo arm (<65 years: 38% vs 21%). Adverse-event and health-related quality of life profiles were consistent between the two age groups.
Overall patient’s age did not impact efficacy of maintenance olaparib, but subgroups were small. In the overall population, no baseline characteristics were predictive of olaparib efficacy in patients aged ≥65 years.
The study was funded by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Abstract S-O3 – Kindler H, Hammel P, Reni M, et al. Maintenance olaparib in patients aged ≥65 years with a germline BRCA mutation and metastatic pancreatic cancer: phase III POLO Trial. ESMO World Congress on Gastrointestinal Cancer 2020 Virtual (1-4 July).