Phase II trial of Pembrolizumab Immunotherapy and Olaparib (POLAR) trial: new data presented at the European Society for Medical Oncology (ESMO) 2024 reveal promising outcomes for patients with metastatic pancreatic cancer (mPC) who have specific genetic mutations or exceptional responses to platinum-based chemotherapy. The trial focuses on patients with homologous recombination deficiency (HRD – when a cell cannot repair damaged DNA properly), non-core HRD (ncHRD – when a cell has some problems with its DNA repair system but not the complete deficiency), and those with an exceptional platinum response, evaluating the efficacy of combining a PD-1 inhibitor (a type of cancer treatment -immunotherapy – that helps the immune system attack cancer cells more effectively) with a PARP inhibitor (which blocks the cancer cell from repairing its damaged DNA, so it cannot divide to make more cancer cells and dies) to enhance progression-free survival (PFS – the length of time during and after the treatment that a patient lives with the disease without it getting worse).

The study enrolled 63 patients divided into three distinct cohorts: (A) patients with HRD mutations including BRCA1/2 or PALB2; (B) patients with non-core HRD mutations such as ATM or CHEK2; and (C) patients without HRD but showing exceptional response to platinum therapy. All patients received pembrolizumab (an immunotherapy drug) and olaparib (a chemotherapy medication) as maintenance therapy following platinum-based treatment.

Cohort A (HRD patients) demonstrated the most promising results, with 64% of patients remaining progression-free at 6 months and an overall response rate (percentage of patients in a clinical trial whose cancer shrinks or disappears after treatment) of 35%. Disease control at six months was achieved in 90% of these patients. In comparison, cohorts B and C showed lower PFS and response rates. In cohort B, 47% of patients were progression-free at 6 months, with a disease control rate of 47%, while cohort C, consisting of platinum responders without HRD mutations, had the lowest outcomes, with only 13% progression-free at 6 months and a 20% disease control rate.

The median overall survival (the length of time from either the diagnosis or the start of treatment that half of the patients in a study are still alive) in cohort A was not reached during the trial, suggesting a potentially sustained benefit for this group. In comparison, cohorts B and C had median overall survival times of 18 months and 10 months, respectively. Most treatment-related adverse events were manageable; however, 36% of patients experienced grade 3/4 events (severe or life-threatening side effects) including anaemia, pancreatitis, and colitis.

Overall, the POLAR trial suggests that pembrolizumab and olaparib may offer substantial benefits, especially for patients with HRD-related mutations, and underlines the need for continued research to optimize treatment strategies for metastatic pancreatic cancer.

References

1. Park, W. et al. Phase II trial of Pembrolizumab and OLApaRib (POLAR) maintenance for select patients (pts) with metastatic pancreatic cancer (mPC) with (A) homologous recombination deficiency (HRD), (B) non-core HRD (ncHRD) and (C) exceptional response to platinum. Annals of Oncology, Volume 35, S922.

Author:
Ana Martins