Study: Combination maintenance therapy may benefit some people with metastatic pancreatic cancer

RELEVANCE

Most relevant for: People with metastatic pancreatic cancer whose have an inheiterd or tumor mutation in BRCA1, BRCA2 or PALB2 whose cancer has not worsened after chemotherapy.

Relevance: Medium

Strength of Science: Medium-High

Research Timeline: Human Research

What is this study about?

This study looked at whether combining two cancer treatments could help keep metastatic pancreatic cancer from growing after initial chemotherapy. The treatments were Keytruda (pembrolizumab), an immunotherapy that helps the immune system recognize and attack cancer cells, and Lynparza (olaparib), a PARP inhibitor that targets cancers with certain DNA repair problems.

Why is this study important?

Metastatic pancreatic cancer is difficult to treat, and for most people, the cancer will eventually return after chemotherapy. A small but important group of pancreatic cancers have a mutation in genes involved in repairing DNA damage, such as BRCA1, BRCA2 and PALB2. These cancers may respond better to certain types of chemotherapy and PARP inhibitors. Researchers wanted to learn whether adding immunotherapy to a PARP inhibitor could control cancer growth longer.

Study findings

The POLAR trial enrolled 63 people with metastatic pancreatic cancer whose cancer had not worsened after chemotherapy. Participants were grouped based on genetic changes.

• Group A: 33 people with an inherited or tumor mutation in BRCA1, BRCA2 or PALB2 whose cancer did not worsen after 4 months of chemotherapy.
• Group B*: 15 people with an inherited or tumor mutation in other DNA repair genes whose cancer did not worsen after 4 months of chemotherapy.
• Group C: 15 people without any of these mutations whose cancers did not worsen after 6 months of chemotherapy.

*Genes included ATM, BAP1, BARD1, BLM, BRIP1, CHEK2, FAM175, FANCA, FANCC, NBN, RAD50, RAD51, RTEL1 and MUTYH.

Long-term benefit

The study followed people for a little more than 3 years:

• Group A: Cancers grew just over 8 months later. Overall survival was about 28 months. 
• Group B: Cancers grew about 5 months later. Overall survival was about 18 months.
• Group C: Cancers grew just over 3 months later. Overall survival was about 10 months.

People with a BRCA1, BRCA2 or PALB2 mutation benefited the most from immunotherapy plus a PARP inhibitor. The combination was less effective in people with a mutation in other DNA repair genes or with no mutations in DNA repair genes. This suggests that knowing if there is a mutation—either inherited or in a tumor—may help identify those most likely to benefit from a combination of immunotherapy and a PARP inhibitor after chemotherapy.

What does this mean for me?

The results do not confirm that pembrolizumab plus olaparib should become standard treatment for metastatic pancreatic cancer. However, some people had long-lasting benefits, justifying further research to identify who would most likely benefit from this combination therapy.

• If you have metastatic pancreatic cancer, genetic and tumor testing may help identify treatment options.
• If you have metastatic pancreatic cancer and a BRCA1, BRCA2 or PALB2 mutation, ask your care team whether a PARP inhibitor or a clinical trial may be an option for you.
• If you have not had genetic testing or tumor testing, ask whether testing could help guide your treatment.

Reference

Park W, O’Connor CA, Chou JF, et al. Pembrolizumab and olaparib in homologous-recombination-deficient metastatic pancreatic cancer: the phase 2 POLAR trial. Nature Medicine. 2026;32:1783-1793. doi:10.1038/s41591-026-04299-5.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity. Share your thoughts on this XRAY review by taking our brief survey.

posted 08/27/2026