WCLC 2025 - Posters & ePosters-EP.12.60 Multiple Primary Lung Cancer With Driver Gene Mutations: Is Targeted Therapy Always the Optimal Choice?

EP.12.60 Multiple Primary Lung Cancer With Driver Gene Mutations: Is Targeted Therapy Always the Optimal Choice?

Pdf Summary

This study addresses the therapeutic challenges in managing multiple primary lung cancer (MPLC), which has seen increased detection through widespread CT screening. MPLC often exhibits inter-lesional molecular heterogeneity, complicating treatment decisions, especially regarding the use of targeted therapy.<br /><br />A classic case of synchronous MPLC is presented where a patient had 34 lung nodules suspicious for MPLC. Initial biopsy confirmed lung adenocarcinoma in the right upper lobe with an EGFR L858R mutation. The patient received targeted therapy with osimertinib. After 12 weeks, a mixed response was observed: shrinkage of the main lesion but enlargement of smaller lesions and lymph node progression, making surgery initially unfeasible.<br /><br />Following multidisciplinary team (MDT) consultation, the patient underwent combination chemotherapy and immunotherapy (nab-paclitaxel, carboplatin, and nivolumab) for two cycles, which led to significant lesion reduction and allowed right upper lobectomy. Analysis of a smaller lesion revealed adenocarcinoma without driver mutations, confirming MPLC’s molecular heterogeneity. However, seven months post-surgery, the patient experienced recurrence with aggressive poorly differentiated non-small cell lung cancer lacking driver mutations.<br /><br />The case underscores the limitations of single-agent targeted therapy in MPLC due to tumor heterogeneity. It emphasizes the importance of early, multi-site biopsies to accurately define molecular profiles of individual lesions. For MPLC cases presenting with either multiple driver mutations or both driver-positive and driver-negative lesions, chemotherapy-based combination regimens are preferred over targeted therapy alone.<br /><br />In conclusion, tailored treatment strategies considering molecular diversity are crucial in MPLC management, recommending combination therapy approaches to improve outcomes.

Asset Subtitle

Zi-Rui Ren

Meta Tag

Speaker Zi-Rui Ren

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

multiple primary lung cancer

MPLC

CT screening

molecular heterogeneity

targeted therapy

EGFR L858R mutation

osimertinib

combination chemotherapy

immunotherapy

multi-site biopsy