Genetic characteristics and clinical outcomes of driver mutant oligometastatic non small cell lung cancer treated with combination definitive chemoradiotherapy and targeted systemic therapy.

Abstract

e20676 Background: Treatment of oligometastatic non-small cell lung cancer (omNSCLC) is evolving with increasing use of local therapies to consolidate disease. Our molecular understanding is also improving with better ability to target genetically identified driver mutations. In non-metastatic NSCLC, combined approaches of definitive therapy and targeted agents are being used. However, how to combine these two therapies in omNSCLC is poorly understood. Here we report genomic features and outcomes of driver mutation positive omNSCLC treated with combined chemoradiotherapy (CRT) and targeted agents. Methods: Patients with omNSCLC were included and underwent next generation sequencing. Oligometastatic was defined as five or less metastases. Frequency of driver mutations were calculated. A subset of patients was treated with combined definitive thoracic CRT, stereotactic radiation to metastatic lesions, and systemic therapy to target noted molecular alterations. Median overall survival (mOS) and progression free survival (PFS) were computed using the Kaplan Meier method for these patients. Results: A total of 406 patients were screened and 243 were classified as oligometastatic. Most common driver mutations found within oligometastasis were KRAS (28%; 31% of which were G12C mutations), EGFR (21%; 50% of which were L858R or Exon19Del alterations), MET (6.2%; 33% of which were exon 14 alterations), ALK rearrangements (3%), and RET fusion (0.8%). mOS in driver mutant omNSCLC was 50.9 months, [95% confidence intervals (CI), 45 months – not reached (NR)] vs 21.6 months, [95% CI, 17.2– 29.5 months], p < 0.0001) in those without driver mutations. A subset of six patients underwent definitive thoracic CRT, stereotactic radiation to metastatic sites, and targeted therapy, five with targeted therapy initiated prior to CRT. Sites of metastasis were brain (n = 3), bone (n = 2), and cervical lymph nodes (n=1). Targetable mutations were EGFR (n = 3), ALK (n = 1), RET (n = 1), and MET (n = 1). Median CRT dose was 60 Gy. Treatment was well tolerated, though one patient discontinued treatment early due to esophagitis. No pneumonitis was observed. At last follow up, all patients were alive. All patients with long term control were treated with induction targeted therapy followed by definitive CRT. One patient experienced with rapid progression post CRT, who did not receive induction therapy. mOS and PFS were not yet reached for the cohort. Conclusions: omNSCLC is a frequent presentation of lung cancer, and targetable driver mutations are routinely encountered in this state. These patients are also often amenable to treatment with definitive CRT. An approach of combined CRT and targetable therapy appears to be feasible and tolerated. Early treatment outcomes are promising, however longer term follow up and prospective studies are needed.