Routine genomic testing is feasible, but only a subset of patients benefit

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Published: 3 Jun 2017
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Dr Olivier Trédan - Centre Léon Bérard, Lyon, France

Dr Trédan presents, at a press conference at ASCO 2017 discussing the ProfiLER study; an ongoing clinical trial that uses genomic profiling of tumours to guide treatment decisions for patients with advanced cancer.

To date, 2,676 patients have enrolled in the study, and 1,944 tumours were analysed, including colorectal, gynecologic, breast, brain, and head and neck cancer, as well as sarcoma.

Actionable mutations were found in 1,004 (52%) of tumour samples; 609 patients had only one actionable mutation, and 394 had two or more (up to six), with the most common actionable pathway was the PI3K/mTOR pathway.

Dr Trédan notes throughout that patient access to targeted drugs remains an issue, with only 7% of patients with an actionable mutation receiving it.

Read the news article here.

 

The ProfiLER programme is a multicentric open label prospective trial aiming to implement screening of molecular alterations for a large variety of cancer patients, adult cancer patients as well as children. 2,676 patients with any type of incurable cancer were enrolled between 2013 and May 2017. At the time of the current analysis the genomic profiles were available for almost 2,000 tumours. The primary objective of this trial was to establish the genomic profile of each tumour. DNA extracted from tumours was analysed for point mutation by sequencing and copy number variation by whole array genome CGH. The genomic analysis report provided by molecular biologists was discussed during a molecular tumour board on a weekly basis. This molecular tumour board reviewed the molecular alterations and defined actionable alterations. First, the actionability of a target was defined by the theoretical ability for a drug to target an abnormal protein of the pathway activated by the target.

Here is the [?? 1:24] diagram of the ProfiLER trial. The main reason for molecular screening failure was the inadequate quantity or quality of tumour DNA. Actionable genomic alterations were found in 52% of the tumours. This led to molecular targeted agent recommendations for 676 patients, corresponding to 35% of enrolled patients. Due to the low availability of molecular targeted agents only 7% of patients with genomic profile were accurately treated by the recommended molecular targeted agent at the time of the analysis. I want to point out that this clinical trial is still ongoing. This corresponds to 21% of the patients with treatment recommendations.

The majority of patients were not able to receive the recommended molecular targeted treatment because of the progression of their cancer or because of the lack of treatment slot in dedicated early phase clinical trials.

This is the distribution of all actionable alterations across the most frequent treatment types within the ProfiLER programme. Among the numerous molecular alterations detected the molecular tumour board identified actionable alterations. These alterations are presented here. For the more than 1,000 tumours with at least one actionable molecular alteration 676 patients had a targeted treatment recommendation and this recommendation took into account the medical history of the patient. The targeted agent was mainly targeting the PI3K-MTOR pathway or the angiogenesis related tyrosine kinase receptors.

Of the 676 patients with molecular profiling results 143 patients were subsequently treated with the recommended molecular targeted agent through inclusion into early phase clinical trials or by off label use of the drug. The PI3K-MTOR pathway was the most common pathway targeted by the molecular targeted agent. Of the 143 patients who received the recommended treatment based on the genomic profile the median overall survival from the time of the incurable disease diagnosis was 3.3 years and the five year survival rate for patients treated with the molecular targeted agent was 35%, this is the red curve, compared to 28% for the patients who did not receive the recommended molecular targeted agent. But, again, those patients who did not receive the molecular targeted agent it was due to disease progression or because of the low availability of the molecular targeted agent. So we cannot compare both curves but we have a signal saying that we could treat the patients and if we could treat the patients perhaps the patients who receive the recommended molecular targeted agent may have a benefit in terms of overall survival.

In conclusion, I want just to highlight that more than 50% of the tumours had a molecular alteration that are potentially actionable. However, screening heavily pre-treated advanced cancer patients limits the number of patients who could actually receive the molecular targeted agent. Thank you for your attention.