The patients who did experience a response following treatment with rucaparib had something in common, however: none had suffered disease progression on earlier platinum-based chemotherapy and one had not received platinum prior to PARP inhibition, suggesting that platinum sensitivity could be linked to PARP inhibition efficacy. If that association holds true in larger studies, it would have important clinical implications.

“This was a very small number of patients, so we only have [a] pattern [and it is] not definitive, but I think the most important thing we saw was that patients who were still sensitive to platinum seemed to be the ones who benefited from PARP inhibition,” Dr Shroff explained.


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That suggests the timing of PARP inhibition could be an important consideration, Dr Shroff said.

Ongoing studies with other PARP inhibitors as a maintenance therapy for patients whose disease responded and who did not progress on standard FOLFIRINOX (a combination regimen of fluorouracil [5-FU], leucovorin, irinotecan, and oxaliplatin) should clarify matters.

“I think [maintenance PARP inhibition after response with FOLFIRINOX without disease progression] is a really smart approach,” Dr Shroff said.

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“The other question is, can you combine PARP inhibitors with chemotherapy — with a platinum, for instance — in up-front settings?” she added. “I think the platinum story is similar to what we saw in ovarian cancer with sensitivity and the utility of PARP inhibition. I don’t think it’s a vastly different story. We use more cisplatin and carboplatin in gynecologic cancers than what we use in pancreatic cancer and I don’t think we really understand yet how [the use of these agents] plays into [sensitivity to PARPs].”

Any patient with a family history that suggests the presence of BRCA1/2 mutations should undergo germline and somatic sequencing, Dr Shroff advised.

“I think we are realizing [mutations in BRCA 1/2 are]  much more common than we initially realized — ‘common’ being perhaps 10% to 15% of patients if you include somatic mutations,” she explained. “But in a disease where we have more than 40,000 people dying each year, that is a sizable population.”

Dr Shroff discusses up-front platinum therapies with any patient whose pancreatic cancer has “a BRCA-like phenotype.”

“That impacts my treatment decision-making,” she said. “I think it’s really important for oncologists to keep that at the front of their minds: BRCA is not as rare in pancreatic cancer as we once thought it was. And if we’re not looking for it, we’re not going to find it.”

References

  1. The National Cancer Institute (NCI). Pancreatic Cancer Treatment (PDQ®)—Health Professional Version. https://www.cancer.gov/types/pancreatic/hp/pancreatic-treatment-pdq. Updated May 24, 2018. Accessed July 20, 2018.
  2. Subramani R, Camacho FA, Levin CI, et al. FOXC1 plays a crucial role in the growth of pancreatic cancer. Oncogenesis. 2018;7(7):52. doi: 10.1038/s41389-018-0061-7
  3. Li J, Byrne KT, Yan F, et al. Tumor cell-intrinsic factors underlie heterogeneity of immune cell infiltration and response to immunotherapy. Immunity. 2018;49(1):178-193.e7.
  4. Shroff RT, Hendifar A, McWilliams RR, et al. Rucaparib monotherapy in patients with pancreatic cancer and a known deleterious BRCA mutation [published online May 16, 2018]. JCO Precis Oncol. doi: 10.1200/PO.17.00316