Preliminary findings from MyPathway, an ongoing phase II basket trial, indicate that matching molecular abnormalities of patients' tumors to relevant targeted therapies—albeit outside a given drug's FDA-approved indication—is both feasible and promising. Notably, patients with HER2-amplified colorectal, bladder, and biliary cancers responded well to the combination of trastuzumab and pertuzumab.

Preliminary findings from MyPathway, an ongoing Genentech-sponsored phase II basket trial, indicate that matching molecular abnormalities of patients' tumors to relevant targeted therapies—albeit outside a given drug's FDA-approved indication—is both feasible and promising. The results were presented by John Hainsworth, MD, a senior investigator at Sarah Cannon Research Institute in Nashville, TN, during the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, IL, June 3–7.

“The same mutations for which targeted agents have been approved for specific cancers can be found in other tumor types—but usually at a lower incidence,” Hainsworth said. “With an increase in comprehensive genomic profiling over the last few years, identifying sufficient patients to test these drugs' potential efficacy in nonindicated tumors has become easier.”

Hainsworth reported data on MyPathway's first 129 patients, who had molecular abnormalities in HER2, BRAF, Hedgehog, or EGFR. They were matched to corresponding Genentech drugs: dual HER2 blockade with trastuzumab (Herceptin) plus pertuzumab (Perjeta); the BRAF inhibitor vemurafenib (Zelboraf); the Hedgehog inhibitor vismodegib (Erivedge); and the EGFR inhibitor erlotinib (Tarceva). All patients had tumor types outside of current indications for these therapies and were refractory to standard treatment options.

Twenty-nine patients with 12 types of advanced cancer achieved an objective response'tumor shrinkage of 30% or more'to their matched therapy, and another 40 saw their disease stabilize. There were responders in each of the four treatment arms, Hainsworth noted, and overall, no new side effects were observed with these therapies.

The most promising results were observed in patients with HER2-amplified tumors'seven of 20 with colorectal cancer, three of eight with bladder cancer, and three of six with biliary cancer had objective responses to trastuzumab plus pertuzumab.

Encouraging data was also seen in patients with BRAF-mutant non–small cell lung cancer (NSCLC): Three of 15 patients responded to vemurafenib, and two more had stable disease.

Based on these findings, the study investigators are enrolling additional patients with HER2-amplified colorectal, bladder, and biliary cancers, as well as patients with BRAF-mutant NSCLC. They'll also add the MEK inhibitor cobimetinib (Cotellic) to vemurafenib'a combination currently approved for advanced or unresectable melanoma'for the study's BRAF-mutant arm. Using ado-trastuzumab emtansine (T-DM1; Kadcyla) in the HER2-amplified arm is another possibility.

Sumanta Kumar Pal, MD, a medical oncologist at City of Hope Comprehensive Cancer Center in Duarte, CA, noted that trials like MyPathway include NCI-MATCH and ASCO's TAPUR study. “It's too early to draw any firm conclusions, but if the results hold, we may see a shift in the long-standing paradigm of treating patients based on their cancer type,” he said. –Alissa Poh

For more news on cancer research, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/content/early/by/section.

©2016 American Association for Cancer Research.
2016
American Association for Cancer Research.