Dr Patel on the Unmet Need in EGFR+ Transformed Small Cell Lung Cancer

“Historically, what to do in this space is quite controversial, and we don’t yet have the best answer.”

Sandip Patel, MD, professor of medicine and medical oncologist at the University of California San Diego, discussed key unmet needs and open questions surrounding EGFR-mutant non–small cell lung cancer (NSCLC) that has transformed to small cell lung cancer (SCLC), a topic covered in the Bridging the Gaps in Lung Cancer meeting.

Patel emphasized that EGFR-transformed SCLC represents a highly unmet need in the field, one that lacks adequate therapeutic options. Clinically, he noted, suspicion for transformation typically arises in 2 scenarios: patients found to have a baseline RB mutation, which confers a higher risk of transformation, or patients who had been responding well to therapy but then experience a sudden, aggressive spread of disease, potentially signaling a transformation event.

Patel noted that management in this space has historically been controversial, and the field still lacks a clear best approach. He added that although novel antibody-drug conjugates (ADCs) are being developed for more traditional, smoking-related SCLC, their efficacy specifically in EGFR-mutant NSCLC that has transformed to SCLC remains undefined, reinforcing the unmet need.

Regarding DLL3-targeted bispecific T-cell engagers such as tarlatamab-dlle (Imdelltra), Patel pointed out that some available data suggest reduced efficacy in this transformed population compared with smoking-related SCLC, marking it as an open area warranting further investigation.

Looking ahead, Patel stated that as more therapeutics become available for SCLC, particularly novel ADCs, it will be important to consider how these agents might be applied to this patient population. He highlighted combining such agents with third-generation, CNS-penetrant, oral small molecule inhibitors as a potentially important combinatorial strategy moving forward.