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Targeted Therapies Continue to Show Potential for Less Common Drivers in NSCLC

Caroline Seymour
Published: Tuesday, Sep 18, 2018

Josephine L. Feliciano, MD

Josephine L. Feliciano, MD

Clinical familiarity with driver mutations, including BRAF V600 and ROS1, continues to grow as seen with FDA approvals of novel therapies, according to Josephine L. Feliciano, MD, an assistant professor of oncology at Johns Hopkins Medicine. Other molecular targets, including RET, MET, and NTRK, continue to be explored with new agents.

State of the Science Summit™ on Advanced Non–Small Cell Lung Cancer, Feliciano spoke about both established and emerging therapeutic developments for patients with less common driver mutations, also acknowledging the importance of rebiopsying in directing therapy decisions.

OncLive: What therapies are available for some of these uncommon mutations?

Feliciano: BRAF V600 [is a] mutation that is also found in other cancers, such as melanoma and cholangiocarcinoma. The study I focused on [in my presentation] included both a BRAF and MEK inhibitor—dabrafenib and trametinib for patients with BRAF V600–positive NSCLC. Essentially, that combination was approved by the FDA for patients with BRAF V600 mutations based on very high response rates.

Are therapies in melanoma also successful in NSCLC?

Yes. What we are also seeing is that many of these drugs and trials are starting to become less cancer-specific. They’re starting to incorporate broader categories of malignancies, but with the same driver mutation.

What options are available for those with ROS1 fusions?

ROS1 is a mutation similar to an ALK translocation. It has a similar configuration in the receptor. Many of the TKIs that are effective for ALK are similarly effective for ROS1. Crizotinib is approved for patients with ROS1 mutations. It’s effective, has high response rates, and has long durations of response for NSCLC. This mutation occurs in about 1% of NSCLC and tends to be mutually exclusive of ALK translocations.
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