ASCO Urges Routine dMMR Testing for Second-Line Metastatic Pancreatic Cancer

Jason Harris
Published: Monday, Nov 05, 2018
Davendra Sohal, MD, MPH

Davendra Sohal, MD, MPH

Based on fresh studies in the setting of metastatic pancreatic cancer, the American Society of Clinical Oncology (ASCO) now recommends routine testing for mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H) for candidates for checkpoint inhibitor therapy.

The updates to the guidelines, which were last reviewed in 2016, include a recommendation for the PD-1 immune checkpoint inhibitor pembrolizumab (Keytruda) for patients who test positive for dMMR or MSI-H.1

For patients who received first-line treatment with gemcitabine plus nab-paclitaxel (Abraxane) and meet other criteria, additional updates call for using fluorouracil plus irinotecan when the secondline combination of fluorouracil plus nanoliposomal irinotecan is unavailable. Those additional criteria include an ECOG performance status (PS) of 0-1, a favorable comorbidity profile, patient preference for this treatment, and a support system for aggressive medical therapy. Fluorouracil plus oxaliplatin (Eloxatin) also may be considered as second-line therapy for patients who had first-line treatment with nab-paclitaxel.1

The changes reflect the ASCO expert panel’s attempt to recommend the appropriate therapy for patients with metastatic pancreatic cancer who experience either disease progression or intolerable toxicity with prior regimens.

Table. Updated ASCO Recommendations for Metastatic Pancreatic Cancer in Second Line

Table. Updated ASCO Recommendations for Metastatic Pancreatic Cancer in Second Line
The updates are based in part by findings of 2 studies. One, a phase II study by Le et al, explored the efficacy of PD-1 inhibition in patients with advanced dMMR cancers across 12 solid tumor types, including pancreatic cancer.2 The other, the phase III PANCREOX trial, evaluated survival outcomes for patients with advanced pancreatic cancer assigned to fluorouracil and oxaliplatin administered as modified FOLFOX6 (mFOLFOX6; infusional fluorouracil, leucovorin, and oxaliplatin) versus fluorouracil plus leucovorin.

Testing for MSI

“For second-line treatment of metastatic pancreatic cancer, our first recommendation now is to consider testing for MSI in patients who are candidates for checkpoint inhibitor therapy,” Davendra Sohal, MD, MPH, director of the Clinical Genomics Program at Cleveland Clinic Taussig Cancer in Ohio and cochair of the expert panel that wrote the new guidelines, said in a podcast. “Any standard form of testing is acceptable, whether immunohistochemistry [IHC], polymerase chain reaction [PCR], or next-gen sequencing.”

In the study by Le et al, across the 12 tumor types, 86 patients with previously treated disease were enrolled and received 10 mg/kg of pembrolizumab every 14 days. All patients had evidence of dMMR as assessed by either PCR or IHC. Seventy-eight patients were evaluable for response. The overall objective response rate (ORR) for this cohort was 53% (95% CI, 42%-64%), and the disease control rate was 77% (95% CI, 66%-85%). Eighteen patients (21%) had a complete response (CR).2

Among the 8 patients with pancreatic cancer, 2 (25%) had a CR and 3 (37%) had a partial response (PR), for an ORR of 62% and a disease control rate of 75%. One patient had stable disease, and 2 were not evaluable. Median progression-free survival (PFS) and median overall survival (OS) had not been reached in this ongoing study.

“A small, nonrandomized study such as that of Le at al would generally be considered low quality due to the risk of bias associated with nonrandomized study designs and the indirectness resulting from the small number of patients with pancreatic cancer included in the study,” the panel wrote. “Nonetheless, the magnitude of the effect across disease sites in the population of patients with dMMR tumors is strong, and on this basis, the expert panel rated the study quality as intermediate.”

In PANCREOX, adults were randomly assigned to mFOLFOX6 (n = 54) or infusional fluorouracil/ leucovorin (n = 54) at 12 medical centers in Canada.3 All patients were included in the intent-to-treat (ITT) analysis. After a median follow-up of 8.8 months, PFS was nearly identical in the ITT population for mFOLFOX6 versus the fluorouracil/leucovorin cohort (3.1 vs 2.9 months; HR, 1.00; 95% CI, 0.66-1.53; P = .989). The PR rate was 13.2% in the mFOLFOX6 arm compared with 8.5% in the infusional arm (P = .361). There were no CRs, and the ORR was similar between the study arms.

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Online CME Activities
TitleExpiration DateCME Credits
Medical Crossfire®: Navigating Treatment Decisions in Pancreatic Cancer: Key QuestionsJun 29, 20191.5
Community Practice Connections™: 2nd Annual International Congress on Oncology Pathology™Aug 31, 20191.5
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