Matching Treatment to Tumor Abnormalities Seems to Pay Off
THIS IS ENORMOUSLY IMPORTANT . THIS IS PRECISION MEDICINE .MATCHING YOUR TUMOR’S UNIQUENESS AND HITTING IT IN ITS A INDIVIDUAL ACHILLES HEEL A BIT THINK TO READ BUT JUST FOLLOW THE HIGHLIGHTS
A strategy of matching molecular abnormalities in patients’ tumors to therapies targeted to those abnormalities is gaining ground, according to preliminary results of the phase IIb MyPathway study presented at the 2016 ASCO Annual Meeting.1 These are still early days for this “matching” strategy, which is currently being explored in several studies of advanced cancers with few treatment options, but experts believe it holds promise for earlier-stage solid tumors.
Durable responses were observed in four major tumor cohorts: HER2-positive colorectal, bladder, and biliary cancers (treated with trastuzumab [Herceptin] and pertuzumab [Perjeta]) as well as BRAF-mutated non–small cell lung cancer (NSCLC, treated with vemurafenib [Zelboraf]), in particular, patients with the BRAF V600E mutation.
John D. Hainsworth, MD
“Our preliminary results show that treating patients according to tumor alterations independent of tumor type is feasible and important for benefiting unmet medical needs,” stated presenting author John D. Hainsworth, MD, of Sarah Cannon Research Institute, and Tennessee Oncology, PLLC, Nashville. “This approach offers new opportunities to patients with solid tumors that have molecular abnormalities that can be targeted with existing therapies. Activity was observed in patients with 12 different tumor types outside of current indications for these targeted agents.”
MyPathway is evaluating agents that target HER2, BRAF, Hedgehog (Hh), or EGFR pathways in nonindicated tumors with relevant genetic abnormalities. “There are approved treatments that target these pathways for at least one other indication,” stated Dr. Hainsworth.
The MyPathway study, an open-label trial designed to accrue 500 patients, had recruited 129 patients with nonindicated tumor types at the time of this report. All patients had abnormalities in one of the four targeted pathways and were refractory to other treatments.
Overall, 29 of 129 patients (22%) had a major response. Of the 29 patients, 14 progressed after a median of 6 months, whereas 15 patients had ongoing responses at the time of the ASCO meeting, ranging from 3+ months to 11+ months.
Targeted Therapy Based on Molecular Profiles
- Matching treatment to the tumor abnormality rather than the primary site of cancer may achieve responses in patients with refractory cancers.
- This strategy may prove to have a bigger payoff if used earlier in the course of care, especially for patients with incurable cancers and few treatment options.
- Further study is needed to define the optimal role of this approach.
The largest group comprised 61 patients with HER2-positive tumors: colorectal, bladder, biliary, NSCLC, pancreatic, head and neck, and other sites. In this group, overall response rate was 28%, and stable disease for more than 120 days was seen in 15%—for a total clinical benefit rate of 43%.
Patients with HER2-positive colorectal cancer had a median of four previous therapies, Dr. Hainsworth said. In this group, the clinical benefit rate was 50% (overall response rate 35%, stable disease, 15%). “This is a strong signal in HER2-positive colorectal cancer, and there also were strong signals in biliary and bladder cancer,” he said, although the numbers of patients were smaller.
In addition, targeting the BRAF mutation with vemurafenib showed promise. In the 33 patients treated, the overall response rate was 24%, and the stable disease rate was 12%—for a clinical benefit rate of 36%. Six different tumor types responded, including NSCLC, ovarian, unknown primary, colorectal, pancreatic, and head and neck cancers.
Of the 33 BRAF-mutated patients, 19 had the BRAF V600E mutation, and 14 had other BRAF mutations. Among the eight responders, seven had the V600E mutation, whereas one had a different BRAF mutation. ■