The phase 2 POLAR trial evaluated the combination of two targeted drugs:

Pembrolizumab – an anti-PD1 immunotherapy that helps the immune system recognise and fight cancer.

Olaparib – a PARP inhibitor which targets cancer cells with specific DNA repair problems

as maintenance therapy for metastatic pancreatic cancer, focusing on patients with Homologous Recombination Deficiency (HRD). The HRD means the cell can’t properly fix DNA damage. This often happens because of mutations in DNA repair genes such as BRCA1, BRAC2, PALB2.

This trial enrolled 63 patients with metastatic (already spread) pancreatic cancer that had responded to or had stable disease after platinum-based chemotherapy. They were divided into three groups based on the tumour’s DNA features:

• Cohort A – Tumours with “core” DNA repair defects (mutations in BRCA1, BRCA2 or PALB2) – HRD group
• Cohort B – Tumours with “non‑core” DNA repair gene changes (RAD51B, RAD51C, RAD51D, ATM, CHEK2, BAP1, BARD1, BRIP1).
• Cohort C – Tumours without these DNA repair mutations, but that had clearly responded to platinum chemotherapy (platinum‑sensitive).

This split reflects what is already known: some tumours with DNA repair problems respond especially well to platinum drugs and PARP inhibitors, and a very small group with mismatch repair deficiency (about 1%) can benefit from immunotherapy alone.

The strongest results were seen in patients whose tumours had mutations in DNA repair genes (BRCA1, BRCA2 or PALB2) – the main HRD cohort – cohort A. In this group:

• 35% of patients had their tumours shrink
• Some patients lived substantially longer than expected for metastatic pancreatic cancer, about 28 months on average
• After 6 months, 64% of patients were still free from cancer growth, called progression-free survival

Patients from Cohort C (no genetic changes):

• Only 8% responded
• Cancer controlled for about 5 months
• Survival: about 18 months

Patients from Cohort C (no genetic changes):

• About 14% responded
• Cancer controlled for about 3 months
• Survival: about 10 months

The combination was generally manageable but carried a 36% rate of Grade 3/4 (severe or life-threatening) treatment-related adverse effects.  Common severe side effects included anaemia, colitis, and pancreatitis.

The combination of olaparib and pembrolizumab worked especially well in patients with BRCA1, BRCA2, or PALB2 mutations (HRD group). In these patients, many tumours shrank, the disease stayed under control for a longer time, and survival outcomes were encouraging.

In summary, even though the study did not fully meet its original goals, it showed that using a personalised treatment approach based on a patient’s tumour genetics provided long-lasting benefit for a meaningful group of patients, especially those with particular inherited gene mutations.

References

Park, W., O’Connor, C.A., Chou, J.F. et al. Pembrolizumab and olaparib in homologous-recombination-deficient metastatic pancreatic cancer: the phase 2 POLAR trial. Nat Med (2026). https://doi.org/10.1038/s41591-026-04299-5

Author:

Ana Martins