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Effectiveness of Maintenance Olaparib for Germline BRCA-Mutated Pancreatic Cancer Across Age Groups: Additional Analysis of the POLO Trial


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According to an additional analysis from the POLO trial, safety of maintenance olaparib in patients with a germline BRCA1 and/or BRCA2 mutation and metastatic pancreatic cancer is consistent, irrespective of age. Patients aged ≥ 65 years derived long-term progression-free survival benefit and durable tumor response from the maintenance treatment. Study investigators led by Hedy L. Kindler, MD, FASCO, of the University of Chicago, presented these findings during the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer 2020 Virtual (Abstract SO-3).

Hedy L. Kindler, MD, FASCO

Hedy L. Kindler, MD, FASCO

The authors explained that in the phase III POLO study, maintenance treatment with the poly (ADP-ribose) polymerase (PARP) inhibitor provided a statistically significant and clinically meaningful improvement in progression-free survival vs 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 published by Golan et al in The New England Journal of Medicine 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). To better determine the efficacy and safety of olaparib in patients aged ≥ 65 years, the study team performed additional analyses by age group.

Study Methodology

Following at least 16 weeks of treatment with first-line platinum-based chemotherapy, patients without disease progression were randomly assigned to receive maintenance olaparib or placebo until investigator-assessed disease progression or unacceptable toxicity. Progression-free survival and response were assessed by blinded independent central review using modified Response Evaluation Criteria in Solid Tumors version 1.1.

Of 92 patients in the olaparib arm, 28 patients (30%) were aged ≥ 65 vs 13 of 62 patients (21%) in the placebo arm. Fewer older patients had Easter Cooperative Oncology Group performance status 0: 64% of those aged ≥ 65 years in olaparib arm vs 46% in placebo arm, and 73% of those aged < 65 years vs 65%, respectively. Median time from diagnosis to randomization was shorter in patients aged ≥ 65 years: 6.1 months vs 6.8 months; in those aged < 65 years, it was 7.3 months vs 7.1 months. There was no difference in median baseline EORTC QLQ-C30 physical functioning score between age groups.

Progression-Free Survival and Responses

KEY POINTS

  • At 1 year, 21% of patients in the olaparib arm vs 41% of patients in the placebo arm aged ≥ 65 years were progression-free; at 2 years, 21% of patients in the olaparib arm vs 0% of patients in the placebo arm remained progression-free.
  • At data cut-off, response duration among older patients was between 10.2 and 32.2 months, and three of four responses were ongoing.

At data cutoff in January 2019, 3 of 28 patients (11%) aged ≥ 65 years vs 7 of 64 patients (11%) aged < 65 years had received olaparib for at least 2 years.

At 1 year, 21% of patients in the olaparib arm vs 41% of patients in the placebo arm aged ≥ 65 years were progression-free (< 65 years = 39% vs 9%), and at 2 years, 21% of patients in the olaparib arm vs 0% of patients in the placebo arm remained progression-free (< 65 years = 23% vs 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 or complete response to maintenance olaparib vs 3 of 13 patients (23%) in the placebo arm (< 65 years = 14 of 64 patients [22%] vs 3 of 49 patients [6%]).

Among responders aged ≥ 65 years, duration of first-line chemotherapy was between 3.7 and 5.6 months, and baseline characteristics were consistent with those of younger responders.

At data cutoff, response duration among older patients was between 10.2 and 32.2 months, and three of four responses were ongoing.

Safety

In total, 43% of patients treated with olaparib aged ≥ 65 years experienced a grade ≥ 3 adverse event vs 33% of patients in the 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 age did not impact the 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.

Disclosure: The study was funded by AstraZeneca and Merck Sharp & Dohme.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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