COMMENTARY

ASCO Lung Cancer Targeted Therapy Data Expands EGFR and MET

Mark G. Kris, MD

Disclosures

July 29, 2021

This transcript has been edited for clarity.

This is Mark Kris, again reviewing developments presented at the 2021 American Society of Clinical Oncology (ASCO) meeting. In parts 1 and 2, I discussed developments in the fields of locally advanced disease and of immunotherapeutics. Here in part 3, I will cover presentations about targeted therapies for lung cancer.

Some of the new information presented this year is quite hopeful. Two abstracts addressed what you can do for patients with EGFR-mutant lung cancers after progression of disease on osimertinib. Yes, we can look for a specific target and it may be that if we find a target — MET amplification, for example — we could use a targeted agent. If we found a fusion, such as a RET fusion or an ALK fusion, we could use a drug targeting those. But patients with fusions are in the minority, as are patients who have on-target EGFR mutations like C797S. In most patients, we don't know the mechanism.

Two studies presented this year show benefit by using an additional therapeutic approach, whether or not we know the mechanism. Pasi Janne and colleagues presented trial data for patritumab deruxtecan (HER3-DXd), an antibody drug conjugate to the HER3 antibody. The other study, by Joshua Bauml and colleagues, used the bispecific antibody amivantamab plus lazertinib. Lazertinib is a third-generation EGFR tyrosine kinase inhibitor (TKI) similar to osimertinib. In both of those trials, patients who had disease refractory to osimertinib alone achieved approximately 35%-40% response rates with these new therapies.

These are the first medications that have shown good, reproducible benefit in this population. These treatments provide an alternative beyond chemotherapy, which is our standard approach today, and both give hope for the future. Amivantamab is already approved for patients with exon 20 insertion mutations in EGFR and thus is potentially available. Patritumab deruxtecan is still in clinical trials.

The other two presentations I want to highlight involve MET amplification. The first is by Xiuning Le and colleagues, who gave the MET-targeted agent tepotinib to patients with MET amplification, not MET exon 14 splicing mutations. Although there's still some discussion as to what exactly MET amplification means, I believe that MET amplification, identified by a next-generation sequencing test, would be sufficient enough to recommend this agent. Tepotinib is available now. This study found a very good rate of response, more than 40% in patients who have amplification in the MET gene. We knew many years ago that crizotinib was effective in patients with high-level MET amplification, and here is an example with one of the newer agents — in this case, tepotinib.

The second study, by Juergen Wolf and colleagues, was with capmatinib. They found about a 66% overall response rate as initial therapy and between 40% and 50% for second- and third-line therapy. I believe that there is still some uncertainty about how effective these drugs are as first-line therapy; some oncologists still believe that they should be saved for the second line. I would disagree with that. If you found a MET exon 14 splicing mutation — and I would add that if you found a MET amplification — either tepotinib or capmatinib would be useful drugs. If they were available, I would give either of those drugs to patients as initial therapy.

These studies show that the drugs are effective — at least in the same range as you would expect for a combination chemotherapy agent — and that tepotinib works in MET-amplified and MET-mutated cancer. I believe that the same would be true with capmatinib.

So, more good news from ASCO this year, with new uses for available drugs and new drugs in the pipeline marching toward regulatory approval. If you have the capability, the long abstracts, including a special section, along with the paper version of the Journal of Clinical Oncology for this past month, are worth a look. Thank you.

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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