ASCO 2019: Dr. Shah Covers Potentially Practice-Changing GI Cancer Studies

Manish A. Shah, MD, director of gastrointestinal (GI) oncology and chief of Solid Tumor Service at Weill Cornell Medicine/NewYork-Presbyterian Hospital, discusses potentially practice-changing studies that were presented at the 2019 ASCO Annual Meeting in GI cancers.

In the phase III POLO trial, maintenance olaparib (Lynparza) significantly improved progression-free survival (PFS) compared with placebo in patients with BRCA-mutated metastatic pancreatic cancer. The study showed that the median PFS with the PARP inhibitor was 7.4 months compared with 3.8 months in the placebo arm (HR, 0.53; 95% CI, 0.35-0.82; P = .0038). Moreover, 22.1% of patients treated with olaparib remained free from progression after 2 years.

Patients in the study were previously treated with FOLFIRINOX, and if they had stable disease were randomized to olaparib or best supportive care. Shah calls this study practice-changing for the 5% to 10% of patients with metastatic pancreatic cancer who harbor BRCA1/2 germline mutations. As a result of the POLO trial and similar precision medicine-based studies, ASCO and the National Comprehensive Cancer Network guidelines suggest that all patients be tested for BRCA1/2 mutations and other genetic alterations.

Switching gears to advanced gastroesophageal cancer, Shah calls the GO2 study pivotal because it focuses on a population of unmet need. Elderly, frail patients typically cannot tolerate standard doses of chemotherapy, so GO2 evaluated low-dose oxaliplatin and capecitabine. Efficacy with the low-dose therapy was similar to standard approaches, with a much more favorable toxicity profile, Shah says.

Immunotherapy also appears to be making headway in this space, due in large part to recent findings of the phase III KEYNOTE-062 study. In the trial, frontline pembrolizumab (Keytruda) was shown to be noninferior to standard chemotherapy in patients with PD-L1—positive, HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma.

Notably, the PD-1 inhibitor also showed a clinically meaningful improvement in overall survival among patients with tumors that had high levels of PD-L1 expression. At 2 years, 39% of PD-L1—high patients were alive on pembrolizumab versus 22% of those on standard chemotherapy. In addition, the agent showed an improved safety profile compared with chemotherapy.

Another study compared laparoscopic surgery versus open surgery in patients with colorectal cancer and liver metastases. Although laparoscopic surgery has been promising, the procedure can be challenging. The randomized OSLO-COMET study showed that there was no detriment to doing laparoscopic surgery in this patient population. As such, Shah says it is feasible to use this technique at an experienced center.

Shah concludes that the benefit seen across GI malignancies is due to the thousands of patients that have enrolled in clinical trials in the last several years.