Progress in Targeted Therapy for Lung Cancer: New Data From ASCO 2020

Mark G. Kris, MD


June 30, 2020

This transcript has been edited for clarity.

I'm Mark Kris from Memorial Sloan Kettering Cancer Center, reporting on the results of targeted therapies for lung cancer from abstracts presented at the 2020 virtual American Society of Clinical Oncology (ASCO) meeting.

To me, the data from the ADAURA trial with osimertinib in the adjuvant setting are important and practice-changing. The potential for this drug to improve outcomes has been there for a long time. This phase 3, randomized trial, presented at the plenary session of ASCO, showed a more than doubling of disease-free survival at 2 years. It shows that we can use therapies in the earlier stages of disease. My continued hope is that, as part of a multimodality program, it can enhance the chance of cure, and this paper goes along to support that hope.

The other important data that came out of this meeting include the proliferation of targets and the proliferation of drugs for those targets. I'm very encouraged that, in just the last many months, we have approved therapies in the United States for NTRK, RET, and MET exon 14, virtually all of which were presented at the meeting.

For RET, at least two abstracts were presented, including one by Gainor and one by Subbiah, for pralsetinib and selpercatinib, which are now approved by the US Food and Drug Administration (FDA). Please note that in the selpercatinib approval, it is available for any line of therapy and should be considered as a first therapy. Looking for RET is important, and we have good drugs.

We had no drugs officially tested and approved for MET exon 14, but that changed with the recent approval of capmatinib. We also saw data presented at ASCO for savolitinib and tepotinib. So, one agent is approved, and two more agents are in the pipeline for MET exon 14. MET exon 14 is an important target. At Memorial Sloan Kettering Cancer Center, we find almost as many MET aberrations as we do ALK aberrations, so it's common in lung cancers.

One particularly recalcitrant target is EGFR exon 20. We saw intriguing data with poziotinib. Unfortunately, it doesn't appear to be crossing the finish line.

Data were also presented for amivantamab. I like this drug not only because it goes after a recalcitrant target but also because it does so in a new way. It is a bispecific antibody targeting MET and EGFR together. I think there is more to see on this and will be important moving forward.

Finally, an abstract by Smit reported the results for trastuzumab deruxtecan. It puts HER2 mutations into that list of actionable mutations for patients with lung cancers. A few years ago at ASCO, my colleague, Bob Li, reported data about using T-DM1. With T-DM1, there was a 44% rate of response; here, with trastuzumab deruxtecan, there was a 62% rate of response. Clearly, there's a response to these agents. More testing is going to happen, but this target is validated and treatment is available.

I will mention a couple of other things about trastuzumab deruxtecan. It's a new concept, at least for lung cancers. Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate. This is also an antibody-drug conjugate, and it brings that class of drugs here. This drug has already been approved for breast cancer. Additional approvals for other disease sites usually move much more quickly. Our hope is that we will ultimately receive FDA approval and very quickly have this agent added to guidelines.

Good news in the targeted therapy field from ASCO this year comes in the form of multiple new targets, multiple drugs, and new constructs. I'm very hopeful that they will provide new tools for us today and in the years to come.

Mark G. Kris, MD, is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York City. His research interests include targeted therapies for lung cancer, multimodality therapy, the development of new anticancer drugs, and symptom management with a focus on preventing emesis.

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