Emerging Therapies for Non-Small Cell Lung Cancer

At the 2021 virtual American Society of Clinical Oncology (ASCO) annual meeting, a broad variety of new studies were presented on non-small cell lung cancer (NSCLC), including the evolving role of EGFR inhibitors and immunotherapy, the benefits of immunotherapy plus chemotherapy, and the impact of immune-related adverse events on clinical outcomes.

In this video, courtesy of VJHemOnc, Benjamin Besse, MD, PhD, of Gustave Roussy Cancer Institute in Paris, discusses what these data might mean for the future of NSCLC treatment.

Following is a transcript of his remarks:

Targeted therapy is part of our management now. We use to screen five different targets, according to the ESMO [European Society for Medical Oncology] guidelines: EGFR, ALK, ROS1, NTRK, and BRAF mutations. But we have seen that there are much more to come. The RET inhibitors, and of course the KRAS G12C [inhibitors].

This interesting data has been updated this year at ASCO. A lot has been said on that. Some might be disappointed by the response rate and the PFS [progression-free survival], but it’s very, very high in these patients that was not supposed to be targeted, in fact — response rate: 37.1%, PFS: 6.8 months.

We can expect the current study in second-line, post-chemo immunotherapy versus docetaxel to be positive according to these numbers, because the tolerance of the drug is good. Very interesting, very small population. Thirteen patients were only treated by immunotherapy, and in this specific population the response rate to, let’s say, first-line sotorasib, at least post-immunotherapy, was 69.2%, which is I think very interesting. And let’s wait to see the data of the drug first-line before any conclusion of the activity of the drug versus chemo/immunotherapy in first line.

Still, a lot of research in the EGFR exon 20 field. We have seen a few drugs that have been presented, like the DZD9008 is the specific EGFR inhibitor. Nice response rate of 40% and only 5% diarrhea. I just want to highlight that the toxicity data that were presented were for any of those levels, so it makes it very low dose of the drug and very high dose of the drug. This is why the toxicity profile seems to be OK. We know that with these specific inhibitors, what is very complicated is to manage the toxicity, so I wait for seeing more data at the RP2D dose, the one that will be developed in the phase II.

In the EGFR field, a drug that is very interesting that has been presented a couple of times and with data that is still coming, is the HER3 ADC [antibody-drug conjugate] patritumab deruxtecan. It’s an antibody directed against HER3, and linked to the drug. Very interesting because HER3 is overexpressed when the patient failed EGFR TKI [tyrosine kinase inhibitor]. The response rate is very nice, 39%. And the PFS is 8.2 months. I think it’s really a drug that can make it because 91% of these patients received an EGFR TKI and the platinum-based chemotherapy. So I think the activity is very impressive. We have seen a bit of [toxicity] with the drug, in particular interstitial lung disease (ILD). It’s something that we are used to now with these new classes of ADC. And let’s see if they are more frequent when the patients were pre-exposed to platinum-based chemotherapy.