Editor’s Note: Anti-PD-(L)1 therapies have been approved for treating advanced non-small cell lung cancer (NSCLC). However, due to limited options, most patients experience disease progression while on anti-PD-(L)1 therapy. At the 2024 European Society for Medical Oncology (ESMO) Annual Meeting, Dr. Pascale Tomasini from the Multidisciplinary Oncology and Therapeutic Innovations department in Marseille, France, presented findings from the PIONeeR trial—a Phase Ib/IIa study targeting specific resistance pathways in PD-(L)1-resistant advanced NSCLC patients. Oncology Frontier interviewed Dr. Pascale Tomasini on the trial’s main findings, the current treatment strategies for advanced NSCLC patients resistant to PD-(L)1 inhibitors, and future directions.

Oncology Frontier: ESMO 2024 presented findings from a Phase Ib/IIa trial on targeting specific resistance pathways (LBA8). How do you view treatment strategies for PD-(L)1-resistant advanced NSCLC patients?

Dr. Pascale Tomasini: I think there is a real unmet need in these situations, as docetaxel is still the standard-of-care. During the last decade, several different options were studied in order to overcome resistance to PD-1 and PD-L1 inhibitors with several different combinations, but no combination has been shown to be better than docetaxel so far.

Oncology Frontier: More clinical trials are available for patients. Does incorporating PD-L1 immunohistochemistry testing help guide treatment for PD-L1-resistant NSCLC patients?

Dr. Pascale Tomasini: Many different combinations are being tested with other checkpoint inhibitors, TIGIT inhibitors and LAG-3 inhibitors, or even with some targeted therapies. I don’t think PD-(L)1 alone would be enough to predict the efficacy of these drugs. I think there is a need for a large biomarker analysis, and to integrate all these biomarkers to be able to find who among the patients are likely to respond and derive benefit from these combinations as compared to docetaxel, which is still the standard.

Oncology Frontier: Could you discuss the unmet needs in the field of PD-L1-resistant NSCLC?

Dr. Pascale Tomasini: Again, there is nothing else other than docetaxel for now in this setting of patients with advanced non-small cell lung cancer resistant to PD-1 and PD-L1 inhibitors. There is a real need for these patients to find something else with less toxicity and better efficacy. Many options are being tested, and I hope with these options and many biomarker analyses, we will be able to improve the strategy for these patients.