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CHICAGO-Researchers reported encouraging early results from a phase II trial that matches patients with molecular abnormalities in the tumor to corresponding targeted treatments. Twenty-nine of 129 patients with 12 different types of advanced cancers responded to drugs outside of FDA-approved indications. The promising responses seen in four tumor types with specific molecular alterations has already led to expansion of these tumor cohorts to additional participants.

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"With genomic testing of tumors becoming increasingly available, studies such as ours will help more patients benefit from precision medicine approaches," said lead study author John D. Hainsworth, MD, senior investigator at Sarah Cannon Research Institute in Nashville, Tenn. "Although it is still early to draw conclusions, our findings suggest that, for example, HER2-targeted therapy could be expanded beyond the current indications of HER2-positive breast and gastric cancers. Our study gives strong early signals for activity of HER2-targeted therapy in HER2-amplified colorectal cancers (those with extra copies of HER2 gene), and possibly other HER2-positive cancers."


Finding a Beneficial Treatment

MyPathway is an ongoing non-randomized, open-label trial that evaluates four treatment regimens in patients with advanced cancer for whom no beneficial treatment is available. This is a nationwide study with 39 currently participating sites.


To be eligible for the study, patients must have had previous molecular studies of the cancer showing abnormalities in the HER2, BRAF, Hedgehog or EGFR pathways. Patients were then matched with drugs targeting those abnormalities. Patients received a combination of trastuzumab (Herceptin) and pertuzumab (Perjeta) if they had HER2 abnormalities (amplification, overexpression, or mutation); vemurafenib (Zelboraf) for BRAF mutations; vismodegib (Erivedge) for Hedgehog pathway mutations; and erlotinib (Tarceva) for EGFR mutations. Only tumor types outside of current indications for these treatments were eligible.


Emerging Regimens

Among the first 129 patients enrolled in the study, 82 had alterations in HER2, 33 in BRAF, 8 in Hedgehog and 6 in EGFR. All patients had an advanced solid tumor and had received a mean of three prior therapies. A total of 29 patients with 12 different types of cancer responded to targeted treatment. Fourteen responders have progressed after a median of 6 months of treatment (range 3-14 months); 15 responses are ongoing at 3+ to 11+ months.


The most promising efficacy was seen among patients with HER2 abnormalities-7 of 20 patients with colorectal cancer, 3 of 8 with bladder cancer, and 3 of 6 with biliary cancer experienced objective responses (tumor shrinkage of 30% or more). Based on these results, recruitment to each of these groups has been expanded.


The group of patients with lung cancer and BRAF mutations will also be expanded. Among the first 15 patients in that group, three had objective responses and two had stable disease (cancer neither shrinking nor growing) lasting for at least 4 months.


The study is designed to accrue up to 500 patients. Groups that show low benefit will be stopped early, while groups that demonstrated efficacy will be expanded. The researchers also plan to incorporate emerging new regimens targeting these pathways. For example, cobemetinib, a MEK inhibitor, will soon be added to vemurafenib for patients with BRAF mutations. Incorporation of new agents targeting additional molecular abnormalities is also planned in the future.