Timely Initiation of Targeted Therapy for NSCLC Improves Outcomes, Study Finds

A retrospective study of patients with advanced non­–small cell lung cancer (NSCLC) with actionable driver oncogenes found that patients treated with targeted therapy in the first line had better outcomes than those who received nontargeted therapy. The results, presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, also suggest that timely switching to targeted therapy upon receiving biomarker test results vs upon disease progression produced comparable outcomes to first-line targeted therapy.

Patients with advanced NSCLC have been shown to benefit from biomarker-driven targeted therapy vs chemotherapy in real-world clinical settings, the authors noted, but patients must first be tested for actionable driver oncogenes before initiating targeted therapy.

In recent real-world research, patients who had actionable driver oncogenes but started nontargeted therapy prior to receiving biomarker testing results showed suboptimal outcomes, explained study author Thomas Stricker, MD, of Tennessee Oncology in Nashville, while presenting the findings at the ASCO Annual Meeting.

The new study used electronic health record–derived deidentified patient data from the nationwide Flatiron Health database. Patients 18 years or older who were diagnosed with advanced NSCLC between January 2015 and October 2022, had actionable driver oncogenes identified via biomarker testing within 90 days of diagnosis, and who received first-line NSCLC therapy were included in the study. Actionable driver oncogenes included ALK, BRAF, EGFR, RET, MET, ROS-1, or NTRK alterations.

A total of 5156 patients were stratified into groups based on treatments received, with cohort 1 receiving frontline targeted therapy within 42 days of biomarker test results; cohort 2 starting first-line nontargeted therapy prior to or following testing but switching to targeted therapy within 42 days of biomarker test results; and cohort 3 starting nontargeted therapy as frontline treatment and not switching to targeted therapy within 42 days.

Of the overall patient population, 79% were treated in the community setting and 56% underwent next-generation sequencing. The researchers followed up until November 2022 or patient death, and multivariate Cox regression analyses were used to evaluate real-world progression-free survival (PFS) and overall survival (OS) among the cohorts.

In cohorts 1 and 2, the most common actionable driver oncogenes were EGFR and ALK. In cohort 3, the most common were EGFR and BRAF.

Outcomes were similar between cohorts 1 and 2, with a median PFS of 10 months in cohort 1 and 13 months in cohort 2. Median OS was 28 months in cohort 1 and 26 months in cohort 2. Cohort 3 showed significantly worse outcomes vs cohort 1, with a median PFS of 6 months and median OS of 21 months.

“The importance of timely treatment decisions based on actionable driver oncogene detection in lieu of treatment switch at progression was demonstrated by the comparable outcomes observed between patients who received upfront targeted therapy and switched within 42 days of biomarker test results,” Stricker said.

Overall, the findings reiterate the importance of testing patients diagnosed with advanced NSCLC for actionable driver oncogenes and of initiating targeted therapy quickly when targetable biomarkers are found.

“I think opportunities remain to improve the utilization of NGS to identify all actionable driver oncogenes upfront to inform appropriate first-line targeted therapy,” Stricker said. “I think there’s no doubt that starting targeted therapy initially as a first-line therapy in appropriate patients is the right way to go, but our data does suggest that if the results come back later than expected, you may not have missed the boat and can switch and still have good outcomes.”

Reference

Stricker T, Jain N, Yu E, et al. Clinical value of timely targeted therapy (TT) for patients with advanced non-small cell lung cancer (aNSCLC) with actionable driver oncogenes (ADO). J Clin Oncol. 2023;41(suppl 16):6507. doi:10.1200/JCO.2023.41.16_suppl.6507