Precision Medicine Improves Treatment of Advanced Cancers
Targeted treatment shows strongest efficacy in HER2 abnormalities.
Early results from a phase 2 trial indicate targeted precision medicine offers great promise in the treatment of several types of advanced cancers.
The trial, presented Saturday at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, matched patients with specific tumor molecular abnormalities to corresponding targeted therapies. Of the 129 patients enrolled, 29 patients with 12 different advanced cancer types showed a response to drugs outside of the indications for which they were approved by the FDA.
The researchers have already expanded several treatment arms to add additional participants for the most promising responses in 4 tumor types with specific molecular abnormalities.
“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, in a press release. “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.”
The non-randomized, open-label trial analyzed 4 treatment regimens in advanced cancer types where there are no beneficial treatments currently available.
Eligibility requirements were for patients who had previous molecular studies of their cancer showing abnormalities in the HER2, BRAF, Hedgehog or EGFR pathways. These patients were subsequently matched with drugs that target their specific abnormalities.
Patients with HER2 abnormalities (amplification, overexpression, or mutation) received a combination of trastuzumab (Herceptin) and pertuzumab (Perjeta); patients with Hedgehog pathway mutations received vismodegib (Erivedge); patients with BRAF mutations were administered vemurafenib (Zelboraf); and patients with EGFR mutations received erlotinib (Tarceva).
Tumor types outside of their current indications for these treatments were eligible.
Of the first 129 patients enrolled in the study, 82 had HER2 alterations, 33 had BRAF mutations, 8 had Hedgehog mutations, and 6 had EGFR mutations. All of these patients had an advanced solid tumor and received a mean of 3 prior therapies. Of the 29 patients who responded to targeted treatment, 14 responders progressed after a median of 6 months of treatment at a range of 3 to 14 months, while 15 responses are ongoing at 3 plus to 11 plus months.
The most promising efficacy was observed in patients with HER2 abnormalities, in which 7 of 20 patients with colorectal cancer, 3 of 8 patients with bladder cancer, and 3 of 6 patients with biliary cancer showed objective responses with tumor shrinkage of 30% or more. The results prompted researchers to expand recruitment for each of these groups.
The lung cancer and BRAF mutation groups will also be expanded. Of the first 15 patients enrolled in that arm, 3 showed objective responses and 2 had stable disease for at least 4 months.
“This study speaks to the incredible potential of precision medicine to help us identify new treatments, but it also underscores the need to explore this genomic-based testing and treatment approach in a learning environment, like a clinical trial,” said ASCO expert in developmental therapeutics Sumanta Kumar Pal, MD. “It’s likely there are factors that we are not yet aware of that explain why certain patients benefit from targeted therapies while others don’t, even when their tumors have the same abnormality. We need to find these answers so we can match more patients to potentially beneficial treatments and spare patients from treatment that is unlikely to improve or prolong their lives.”