Changing paradigms in first-line lung cancer

The Gathering Around Cancer Conference 2024 brought together national and international experts in diverse areas of cancer to offer the latest research in their fields. This was the 12th iteration of the conference, which took place on 21-22 November at the Croke Park Conference Centre, Dublin, and featured multiple distinguished clinicians and researchers.

The complexities of cancer treatment were reflected in the agenda. This year, there was an increased focus on the interface between clinicians and scientists, patient advocates, and quality-of-life considerations. As in previous years, the agenda was driven by audience feedback to keep the content as relevant as possible.

As always, the standard of young investigators’ research reports was extremely high. The sessions also included content on novel therapies, women’s health, and neoadjuvant approaches.

One of the invited speakers was Dr Adam Schoenfeld of Memorial Sloan Kettering Cancer Centre, New York, US, who spoke on the topic ‘Cell therapy for lung cancer’.

Dr Schoenfeld provided an overview of this therapeutic approach including case studies. “When we think about the paradigm of treatment for first-line lung cancer, it has changed over the years and continues to rapidly change,” he said. “The way I try to simplify things generally is, one, we look for these oncogene drivers. If the patient has one of these oncogene drivers, such as a sensitising EGFR mutation or ALK fusion, we typically treat them with targeted therapy as a first-line treatment.

“If they don’t have one of these drivers, then the treatment depends on a few factors, including their histology and PD-L1 expression. We used to use PD-L1 expression to determine who would get immunotherapy – now, pretty much everyone gets immunotherapy if they don’t have a contraindication, and we use the PD-L1 expression more to decide who will get chemotherapy. If a patient has high PD-L1 expression, sometimes we will avoid using chemotherapy because we think they can derive benefits from just using immunotherapy. If they have low PD-L1, then we typically add in chemotherapy. PD-L1-negative is a more complicated subject, where we often do chemotherapy and sometimes dual checkpoint blockade too.”

Dr Schoenfeld explained that immunotherapy and targeted therapy have revolutionised lung cancer treatments. However, he said even when patients respond to immunotherapy, acquired resistance is common and durable responses are lost.

“Even patients who are many years out [from diagnosis] can develop resistance to immunotherapy,” he said. Similarly, for targeted therapy, resistance is almost inevitable, he added.

He discussed trial data and outlined that the hope with cell therapy in lung cancer is to expand the initial benefits seen with checkpoint blockade in non-oncogene-driven lung cancers, and translate some of those benefits to oncogene-driven lung cancers. Currently, the three main approaches involve tumour-infiltrating lymphocytes (TILs), T-cell receptors (TCRs), and chimeric antigen receptor therapies (CAR-T).

Dr Schoenfeld focused on TIL therapy and told the conference: “There are many unanswered questions that remain around how to move forward with TIL in lung cancer and in solid tumours in general. It would be great to know if there are any potential biomarkers of response in resistance… also, how does prior therapy exposure affect outcomes; does the anatomic site of the TIL collection affect outcomes; and what is the optimal method of manufacturing for product development and safety and efficacy.”

Dr Schoenfeld concluded: “There are some early encouraging efficacy data as a proof of concept for cell therapy in lung cancer, but I think there [is] still substantial room for improvement. One thing that would be helpful would be to try and incorporate some of these treatments earlier and that may improve response rates and durability.”

“We also need efforts to engineer things like TIL therapies to simultaneously increase activity and reduce toxicity. I think TILs, TCRs, and CARs may have different roles in lung cancer in the future.”