Clinical outcomes of patients with -mutant advanced lung cancer: chemotherapies -directed therapies.

BACKGROUND

Lung cancer is now the leading cause of cancer mortality worldwide for both men and women. In non-small cell lung cancer (NSCLC), matching a specifically targeted drug to the identified driver mutation in each patient resulted in dramatically improved therapeutic efficacy, often in conjunction with decreased toxicity. Mutations in have been identified as an oncogenic driver gene for NSCLC. This retrospective study was conducted to better understand the clinical outcomes of advanced lung cancer patients harboring mutations treated with chemotherapies and -targeted agents, as well as the optimal clinical choice.

METHODS

Patients who were diagnosed with advanced lung cancer (stage IIIB/IV) and had undergone molecular testing at Zhongshan Hospital, Fudan University, Shanghai, China from April 2016 to December 2018 were reviewed. For patients that had mutant advanced lung cancer, we analyzed their clinical and molecular features and clinical outcomes, including overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and objective response rate (ORR).

RESULTS

We identified 44 patients harboring mutations. Their median age was 56 years, with the majority being women ( = 24), never smokers ( = 32), and having the adenocarcinoma genotype ( = 42). Amongst the mutations present, a 12 base pair in-frame insertion in exon 20 with p.771insAYVM was the most common subtype in patients with known detail variants of mutation (9/27). The median OS from the date of advanced disease diagnosis was 9.9 months with 24 deaths, and a median follow-up of 12.7 months for survivors. For patients with a known exon 20 insertion mutation, OS tended to be superior (though not statistically) in the first-line -TKI group to that in the group receiving chemotherapy (10.8 9.8 months,  = 0.40). However, patients that received first-line chemotherapy had a median PFS of 5.9 months, numerically longer than that of the -TKI group (4.6 months,  = 0.63). Patients who received -targeted therapy as first-line therapy had an improved OS (10.8 10.1 months,  = 0.30) and PFS (4.6 2.8 months,  = 0.36) relative to those who received -targeted therapy as subsequent-line therapy, although they did not meet the threshold for statistical significance. Furthermore, patients with AYVM mutation were associated with poor clinical outcomes.

CONCLUSION

Pemetrexed-based chemotherapy remains an important component of care for patients with -mutant NSCLC. -TKI given as an initial therapy may bring more clinical benefits than when given as a subsequent-line therapy. Refining the patient population based on patterns of variants may help improve the efficacy of anti- treatment in lung cancer. Developing highly effective and tolerable -targeted agents is urgently needed for this population.