Clin Lung Cancer 2021 Jan 27
Combining Osimertinib With Chemotherapy in EGFR-Mutant NSCLC at Progression.
Abstract
Background
Osimertinib is a third-generation EGFR tyrosine kinase inhibitor that has improved survival and central nervous system (CNS) outcomes in patients with non-small cell lung cancer (NSCLC) with activating EGFR mutations. However, little is known about the efficacy and safety of combining osimertinib with chemotherapy.
Methods
This was a retrospective study performed at 3 institutions. Patients with advanced EGFR-mutated NSCLC who received concurrent osimertinib with chemotherapy in the third-line or beyond were identified by chart review. Efficacy outcomes including duration on treatment (DOT), overall survival (OS), and CNS outcomes were assessed. Safety outcomes were also evaluated.
Results
A total of 44 patients met inclusion criteria. Median DOT with osimertinib plus platinum doublet (n = 28) was 6.1 months (95% CI 4.1 months-not reached), and with osimertinib plus single-agent chemotherapy (n = 29) was 2.6 months (95% CI 1.8-4.8 months). Median OS from the start of osimertinib plus chemotherapy was 10.4 months (95% CI 7.0-13.2 months). At initiation of osimertinib plus chemotherapy, 37 patients (84%) had CNS metastases; 9 of these (24%) had CNS disease progression on osimertinib plus chemotherapy. Chemotherapy was delayed or dose reduced due to toxicity in 8 patients (18%); osimertinib was discontinued in 1 patient (2%) for reduced cardiac ejection fraction, and dose reduced in 2 patients (5%).
Conclusions
The combination of osimertinib plus chemotherapy appeared safe and showed favorable control of CNS disease in this cohort of patients who had progressed systemically with multiple prior lines of therapy, with DOT and survival outcomes similar to historical chemotherapy controls.
Related Questions
How do you approach patients with driver mutation positive, Stage IV NSCLC who don't benefit from upfront first-line TKI?
It depends on the mutation. EGFR mutants after Osimertinib:- If oligometastatic disease: an option is radiation to the oligometastatic spots and continue osimertinib. It is important to re-biopsy as well due to the possibility of small cell transformation. If transformed to small cell, in general, c...
For patients with EGFR mutation positive NSCLC who progress on first line TKI without actionable resistance mechanisms, would you consider chemotherapy + targeted therapy as a second line option, or chemotherapy +/- immunotherapy?
Although the question assumes no actionable changes in the lung cancer, I do refer you to an excellent review of this topic, published last September (Piper-Vallillo et al., PMID 32552277), which included a table listing twenty-five open clinical trials for patients who have developed progression af...