Entrectinib in NTRK fusion-positive non-small cell lung cancer

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Published: 18 Apr 2019
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Dr Luis Paz-Ares - Hospital Universitario Doce de Octubre, Madrid, Spain

Dr Luis Paz-Ares speaks to ecancer at the European Lung Cancer Congress 2019 about an integrated analysis of the STARTRK-2, STARTRK-1 and ALKA-372-001 trials.

Dr Paz-Ares outlines the mechanism of entrectinib in a genetically specific set of patients, and also the benefits specifically to those with CNS metastases.

He finalises by explaining the toxicity profile, but also that this drug should be given to more patients over a wider range of cancer types to provide more data.

Entrectinib in NTRK fusion-positive non-small cell lung cancer

Dr Luis Paz-Ares - Hospital Universitario Doce de Octubre, Madrid, Spain

This presentation is about the role of entrectinib, an NTRK inhibitor, specifically in patients with lung cancer. We know that the drug is active in patients whose tumours get fusions in this protein which activate the signalling of NTRK. Those tumours typically respond pretty well to NTRK inhibitors such as entrectinib. In a trial that we are presenting here, a collection of three trials, the response rate in 54 patients is 57% and out of them some ten patients were actually lung cancer patients of non-squamous or squamous histology. In this population the response rate was 70%, a bit higher than in the overall population, and, importantly, the response rate on the CNS metastases was 67%. So that means the response rate, the efficacy, has been confirmed not only in patients with lung cancer but among the lung cancer patients among those with CNS metastases which is a frequent issue in this population.

How might this affect the clinical landscape?

This approach, because NTRK aberrations are not frequent in lung cancer but for the small proportion of patients that do have this genomic abnormality we’ve got drugs which are active and we know larotrectinib is active in this population. Specifically we’ve got enough patients in this population to say the data is confirmed on lung cancer with this specific genomic aberration. Once the drug is approved physicians and patients can benefit from it.

Where will this research be in three years?

We have to increase the number of patients treated, not only with lung cancer but with other solid tumours, particularly sarcomas, some salivary gland tumours but also breast cancers and so on.

How is the toxicity?

Importantly as well the safety profile is pretty favourable and the side effects are typically class side effects.