No benefit of rilotumumab in MET-positive gastric cancer

Last Updated: 2017-10-09

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Patients with MET-expressing gastric or gastroesophageal cancer do not fare better when rilotumumab is added to their medication regimen, new research suggests.

"Ligand-blocking inhibition of the MET pathway with rilotumumab is not effective in improving clinical outcomes in patients with MET-positive gastric or gastro-oesophageal adenocarcinoma," Dr. Daniel V.T. Catenacci of the University of Chicago and his coauthors write in The Lancet Oncology, online September 25.

For the phase 3 RILOMET-1 trial, conducted at 152 centers in 27 countries, the researchers recruited adults who had unresectable locally advanced or metastatic gastric or gastrooesophageal junction adenocarcinoma, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, MET-positive tumors, and evaluable disease - and who had not already received systemic therapy.

They randomly assigned 609 such patients to receive either rilotumumab or placebo - plus open-label chemotherapy with epirubicin, cisplatin, and capecitabine - in 21-day cycles for up to 10 cycles.

After completing chemotherapy, participants continued to receive rilotumumab or placebo monotherapy until their disease progressed, they could not tolerate the treatment, or they withdrew consent.

After an independent data monitoring committee found more deaths in the rilotumumab group, participants in that group discontinued all study treatment. Median follow-up was 7.7 months in the rilotumumab group and 9.4 months in the placebo group.

Median overall survival was 8.8 months with rilotumumab and 10.7 months with placebo (P=0.003).

The most common grade 3-5 adverse events were neutropenia, anemia, and fatigue - with roughly similar percentages in both groups. Serious adverse events occurred in about half of both groups.

Deaths due to adverse events occurred in 14% of the rilotumumab group and 10% of the placebo group. Mortality related to disease progression occurred in 11% and 8%, respectively.

Dr. Davendra Sohal of Cleveland Clinic, in Ohio, told Reuters Health by email that the trial "showed no benefit - in fact, it showed detriment - from rilotumumab. The take-home point," he said, "is that MET did not prove to be a therapeutic target. HER2 remains the only molecular target in esophagogastric cancers."

Dr. Sohal, who was not involved in the study, noted that such findings, though disappointing, are not new. "In fact," he said, "most targeted therapies (except trastuzumab) have failed in this setting."

Dr. Axel Grothey of Mayo Clinic in Rochester, Minnesota, who coauthored an accompanying commentary on the study, told Reuters Health in a phone interview, "This rigorous testing of a new targeted therapy in a randomized study left no doubt that with this approach there was no benefit."

"It is not clear whether this class of agents has a chance to be effective in this malignancy," Dr. Grothey added. "It is very difficult to develop targeted agents in gastric cancer."

"Could the targeted agent have had a better chance to succeed with better patient selection?" he asked. "Unfortunately, we have seen more disappointments in oncology than happy surprises, with the exception of some patients on immunotherapy now," he said.

"Many studies are being conducted now in gastric cancer," Grothey offered. "Moving forward, we are focusing on immunotherapy, including for gastric cancer. But most patients still do not benefit from immunotherapy, so the next step . . . is combining immunotherapy with targeted agents or with chemotherapy."

Dr. Sohal added that the role of immunotherapy is the most exciting news in this area. "Pembrolizumab has FDA approval now for use in microsatellite instability-high (MSI-H) tumors, as well as PD-L1 expressing (combined positive score 1 on IHC) esophagogastric cancers," he noted. "Therefore, for all eligible esophagogastric cancer patients, we now test MSI and PD-L1 status routinely to see if immunotherapy may be an option for second-line management."

Amgen, maker of rilotumumab, funded the study.

SOURCES: http://bit.ly/2y4PcZK and http://bit.ly/2fSiYqS

Lancet Oncol 2017.