Discordances between molecular profiling and precision oncology drug selection of non-small cell lung cancer in China

Background: Precision oncology drugs are a class of targeted drugs that are most effective in a molecularly defined subset of cancer patients. Pretreatment molecular profiling is integral to optimal patient selection. However, discordances between molecular profiling results and actual drug selection become evident in clinical practice. This study aimed to assess the discordances between molecular alterations and actual drug selection of non-small cell lung cancer (NSCLC) in China. Methods: This retrospective cohort study consecutively included NSCLC patients from a specialized oncology hospital and a general hospital in Beijing between November 2021 and June 2022. Discordances between molecular profiling results and first-line drug selection consisted of the following four scenarios: (1) not receiving any drugs after molecular profiling; (2) receiving precision oncology drugs before getting molecular profiling results or without molecular profiling results; (3) receiving precision oncology drugs without any targeted gene mutations; (4) not receiving precision oncology drugs with targeted gene mutation. Primary outcome was the proportion of discordances of included NSCLC patients in China. Secondary outcomes were the proportion of four scenarios of discordances. Findings: A total of 707 NSCLC patients were included, of whom 519 were diagnosed with adenocarcinoma, 172 with squamous cell carcinoma, and 16 with other pathological types. The proportion of molecular profiling in NSCLC patients was 62.4% (441/707), with adenocarcinoma patients accounting for the highest percentage at 83.4% (368/441). The proportion of discordances between molecular profiling results and first-line drug selection was 25.2% (178/707). 17.8% (126/707) patients did not receive any drugs after molecular profiling, 1.7% (12/707) received precision oncology drugs before getting molecular profiling results or without any molecular profiling results, 1.1% (8/707) received precision oncology drugs without any targeted gene mutations, 4.5% (32/707) did not received precision oncology drugs with targeted gene mutation. Interpretation: This study highlighted a quarter of NSCLC patients had the discordances between molecular profiling results and first-line drug selection in China, which may result in a loss of survival benefit to the patient, and a waste of the value of molecular profiling. Future studies need to evaluate and intervene the discordances to optimize the implementation of precision oncology therapy.