Precision medicine selection with MyPathway for solid tumours

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Published: 4 Jun 2016
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Dr John Hainsworth - Sarah Cannon Research Institute, Nashville, USA

Dr Hainsworth presents at ASCO 2016, encouraging early results from a phase II trial that matches patients with molecular abnormalities in the tumour to corresponding targeted treatments.

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ASCO 2016

Precision medicine selection with MyPathway for solid tumours

Dr John Hainsworth - Sarah Cannon Research Institute, Nashville, USA


It’s my pleasure to present the preliminary results of an ongoing trial, the MyPathway trial, that’s an open label phase II study looking at several molecularly targeted treatments in patients with advanced cancer.

An increasing number of targeted agents for advanced cancer are in use now based on the presence of molecular abnormalities in the cancers. Examples of major successes in this area included HER2 targeted treatment for HER2 positive breast cancer and BRAF targeted treatment for BRAF mutated melanoma. We’ve known, though, that the same mutations that are in those cancers are found in a wide variety of other cancers although at a lower incidence. It’s been difficult to test how effective these same treatments are in the other cancers due to the difficulty in identifying the patient population. With the increase of comprehensive genomic profiling that has gone on in the last few years, we’re now identifying more and more of these unusual mutations in other cancers and that’s what’s this trial is addressing.

There are four targets that are being addressed in this trial, HER2, BRAF, Hedgehog and EGFR. The four corresponding treatments shown in the second line there on the slide are all drugs and treatments that are in use already and are approved for at least one type of cancer. Patients that are eligible for the MyPathway trial have non-indicated cancer types that contain one of these mutations. These are patients also who have had to be refractory to other standard treatment before being considered for this trial.

This is a summary of all the patients that have been accrued and treated so far, 129 patients, and you can see in those patients 29 actually have had a major response, defined as a shrinkage of the cancer by at least 30%. Responses have been seen with all four of the treatments in this trial, no new safety signals were observed and it’s a little early to know how long the responses are but you can there on the slide that they’re going to be in the range north of six months and probably between six and nine months as we get more follow up on this study.

Two-thirds of the patients had HER2 abnormalities and on this slide the largest group, those with HER2 amplification or over-expression, is shown. 61 patients in this group and you can see on the bottom line the overall response rate in this group was 28%, six different tumour types had responses: colorectal, bladder, biliary, non-small cell lung cancer, pancreas and head and neck cancer. Of particular interest are the top three lines, the biggest groups right now. Colon cancer, these are refractory patients with a median of four previous regimens, 7 of 20 or 35% had responses, an additional 3 had stable disease for more than 4 months for a total clinical benefit rate of 50%. I think that’s a very strong signal there. Although smaller the signal is also strong in bladder and biliary cancer, each with three responses in those groups as well.

Targeting BRAF in these patients was also successful. You can see, of 33 patients we had 8 responders or 24%. In this group also there were six different cancer types that responded to treatment: non-small cell lung cancer, ovarian, unknown primary, colorectal, pancreas and head and neck. The only sizeable group here was the non-small cell lung cancer where 3 of 15 patients or 20% had responses and another 2 had stable disease. Of interest in this group, 7 of the 8 responses were in V600E mutations and, as you know, that’s the mutation that has been specifically correlated with high response to BRAF inhibition in melanoma where this treatment is now approved. So looking at only those patients the response rate here was 38% in this group.

So, in conclusion, we’ve shown now that this trial design is feasible where patients are selected on the basis of molecular abnormalities in their cancers rather than on their primary tumour type or primary site and certainly offers opportunities for patients with these molecular abnormalities. We saw responses in twelve different tumour types already in this trial and in four major categories including HER2 amplified colorectal cancer, bladder cancer and biliary cancer as well as BRAF mutated non-small cell lung cancer. All of these groups met the protocol criteria for efficacy and have been expanded. The MyPathway trial is continuing to accrue patients and just this last week went over 200 patients accrued so far. Thank you.