ASCO 2024: Advances in Targeted Therapy for Lung Cancer

Drs Xiuning Le, Sandip Patel, and Yi-Long Wu discuss exciting data reported out for targeted therapy, especially in lung cancer space, at ASCO 2024.
https://www.medscape.com/viewarticle/...

-- TRANSCRIPT --
Xiuning Le, MD, PhD: Hello. I'm Xiuning Le. I'm an associate professor at MD Anderson Cancer Center in Houston, Texas. I'm a thoracic medical oncologist.

Joining me today are two experts, one from China and one from the United States. First is Dr Yi-Long Wu. He's very famous. He's the director of Guangdong Province People's Hospital, and he's also from Guangdong Lung Cancer Institute.

Our US expert is Dr Sandip Patel. He is a professor of medicine at University of California, San Diego.

Today we're speaking at the 2024 ASCO Annual Meeting in Chicago. It's a really busy meeting, and we have a large amount of new, exciting data reported out for targeted therapy, especially in the lung cancer space.
Let me begin to talk about some of the data that we have recently seen. I will try to group them into topics so that we can have a more informed discussion. First, let's dive into the antibody-drug conjugate (ADC) data that we saw very recently in three back-to-back presentations.

Sandip, can you please give us a quick summary of the results we saw?

Sandip P. Patel, MD: I think we've really had a renaissance in ADCs. These are antibodies, through novel linker chemistry, with multiple cytotoxic payloads delivering chemotherapy directly to the tumor. We have multiple different combination studies that we saw today in thoracic oncology.

The first was the ICARUS-LUNG01 study. This was looking at datopotamab, which is a TROP2-targeting ADC. This is really around the biomarker story because one of the things is, while for antibodies, we have reasonable biomarkers for immunohistochemistry, for example, for ADCs, the biomarker story really hasn't been that clean. Even for HER2, HER2-negative patients can respond.

This is really an effort at describing and better understanding the biomarker story for datopotamab in lung cancer. I congratulate the investigators on some really interesting correlative work, which may define future biomarker selection for studies.

We also had an ADC and a PD-1 combination, the EVOKE-01 study, with sacituzumab govitecan. This is used in breast cancer in the United States, bladder cancer, and now it's being investigated in non–small cell lung cancer. We saw some provocative data in combination with a PD-1 antibody, especially in PD-L1–negative patients, so is this an opportunity to make cold tumors hot, so to speak.

The OptiTROP LUNG01 study, which is a next-generation TROP-2 ADC from Asia that's combined with a PD-1 inhibitor, in my opinion, showed really interesting data across PD-L1 strata. I'm looking forward to seeing how this data translates to the benefit of patients.

What are some of the antibody approaches you're most excited about in your clinic?

Le: Yi-Long, can you please make a comment on your experience with ADCs, and do you think ADCs will be just hype and then become not as exciting over time?

Yi-Long Wu, MD: No doubt, the ADCs are very topical in the oncology field, especially for lung cancer and breast cancer. So far, we also know the HER2 ADC drugs are very successful in breast cancer and lung cancer.

It's interesting if we think about why only the HER2 ADCs are successful and the others are unsuccessful. I think this is very important. I don't know why the other ADCs are not so successful. Maybe one of the reasons is due to the target population based on the antibody and the targets. I think we have the target, but we have an unselected population.

Le: There is a mismatch.

Wu: It may be the reason why so many ADC drugs so far have been under our expectations.

Le: Sandip, what do you think about the promising data of the TROP-2 ADC from Asia in combination with the PD-1 in the frontline setting? I think the data numerically looked very exciting. Do you think a combination with IO will be the direction to go?

Patel: I think so. I think the concerns around the emergent toxicities from ADCs, including lung toxicities such as interstitial lung disease, and how to deconvolute these from immune pneumonitis, are going to be very important. We know from small-molecule EGFR inhibitors that combining those with PD-1 has led to high rates of pneumonitis. How we avoid that as we deal with monoclonal-based strategies, I think, is going to be key.

The other thought — I think this is a great point — is that the biomarkers for ADCs don't seem to predict response as well as biomarkers for the bland antibody. There's some sort of synergy from this bystander payload effect that we don't yet have a biomarker to measure.

Transcript in its entirety can be found by clicking here:
https://www.medscape.com/viewarticle/...