ESMO 2022 | Highlights in lung cancer at ESMO 2022
Sanjay Popat, MBBS, FRCP, PhD, The Royal Marsden NHS Foundation Trust, London, UK, shares his highlights in lung cancer from the European Society for Medical Oncology (ESMO) 2022 Congress, including the Phase II INSIGHT 2 (NCT03940703) trial investigating tepotinib plus osimertinib in osimertinib relapsed MET amplified non-small cell lung cancer (NSCLC). The trial demonstrated a response rate of approximately 55% with the combination of tepotinib plus osimertinib and after a 9-month follow-up the median duration of response had not been reached, suggesting a highly active approach for patients with EGFR-mutated NSCLC who had relapsed on osimertinib due to MET amplification. Further, tepotinib monotherapy was not effective, suggesting synergy between tepotinib and osimertinib. This interview took place at the European Society for Medical Oncology (ESMO) 2022 Congress in Paris, France.
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Transcript (edited for clarity)
So here at the ESMO meeting we’ve had a number of great datasets and I think two of the link datasets were presented at the metastatic oral session. One was the update of the INSIGHT 2 cohort, looking at the combination of osimertinib with tepotinib in MET-amplified EGFR-mutant tumors. Now we know that MET amplification is an acquired resistance mechanism to EGFR-mutant tumors that relapse on osimertinib...
So here at the ESMO meeting we’ve had a number of great datasets and I think two of the link datasets were presented at the metastatic oral session. One was the update of the INSIGHT 2 cohort, looking at the combination of osimertinib with tepotinib in MET-amplified EGFR-mutant tumors. Now we know that MET amplification is an acquired resistance mechanism to EGFR-mutant tumors that relapse on osimertinib. And the question is, what is the benefit of adding a MET inhibitor? INSIGHT 2 study took these patients with MET amplification defined by FISH or NGS, and looked at tepotinib monotherapy or tepotinib with combination osimertinib. The combination looks highly active with the response rate of around 55%, and after nine months of follow up, the median duration of response has not yet been reached, suggesting that we really have a very active combination here.
And what was even more important was that tepotinib monotherapy did not have much in the way of activity at all. So really it is the synergy between tepotinib and osimertinib because MET amplification seems to be a subclonal event from the biological basis that seems to be driving that efficacy that we can see. So I’m delighted to see that activity and both drugs seem to be tolerable at the standard doses. Joined to that was a dataset presented by Dr. Petruska and colleagues looking at the genotyping information on patients that relapse on osimertinib, re-biopsying them. What it demonstrated is that re-biopsies are not straightforward. Only about 38% of patients that started osimertinib could have re-biopsy. We don’t have data on histological transformation as yet, and we look forward to that in due course, but it did demonstrate that MET amplification occurs at about 20% rate. And so now we know that benchmark of the rate of MET amplification. We’ve also got a potentially great treatment for it (combination to tepotinib with osimertinib), and very excited to see that data.
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