1. The median overall survival was 17.6 months in the gefitinib group vs 27.5 months in the gefitinib plus chemotherapy group, with HR 0.58 (significant).

2. The 5-year progression-free survival was 1.71% in the gefitinib group vs 6.67% in the gefitinib plus chemotherapy group, with HR 0.53 (significant).

Evidence Rating Level: 1 (Excellent)

Study Rundown: The standard initial treatment for EGFR-mutant advanced non–small-cell lung cancer (NSCLC) involves an oral tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR), however, there is some evidence of potential improvement in outcomes by combining it with pemetrexed and carboplatin chemotherapy. This paper is an update to a previous phase III trial which explored this. The primary endpoint was progression-free survival (PFS) and secondary endpoints included overall survival (OS). The median follow-up time was 5.0 years. Median OS was 17.6 months in the gefitinib group vs 27.5 months in the gefitinib plus chemotherapy group (p< .001). The 5-year OS was 4.42% in the gefitinib group vs 13.04% in the gefitinib plus chemotherapy group, with HR 0.58 (significant). Similar results were found regardless of EGFR variation type and brain metastases. The 5-year PFS was 1.71% in the gefitinib group vs 6.67% in the gefitinib plus chemotherapy group, with HR 0.53 (p< 0.001). 74.4% in the gefitinib group vs 57.5% in the gefitinib plus chemotherapy group received further therapy. The strength of this study included its follow-up time, and the limitations included the small sample size and lack of other endpoint data like safety. Overall, this update continues to show outcome benefit to adding chemotherapy to gefitinib in adults with advanced NSCLC harbouring an EGFR mutation.

Click to read the study in JAMA Oncology

Relevant Reading: Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC

In-Depth [randomized controlled trial]: This single-center phase III trial enrolled adults with advanced NSCLC with an EGFR mutation and randomized them (1:1) to gefitinib (n=176) or gefitinib plus pemetrexed/carboplatin or four cycles, followed by maintenance pemetrexed (n=174). The median follow-up time was 5.0 years. Median OS was 17.6 months (95%CI, 15.3-21.5) in the gefitinib group vs 27.5 months (95%CI, 24.8-30.8) in the gefitinib plus chemotherapy group (p< .001). The 5-year OS was 4.42% (95%CI, 1.98-8.39) in the gefitinib group vs 13.04% (95%CI, 8.27-18.9) in the gefitinib plus chemotherapy group, with HR 0.58 (95%CI, 0.46-0.72). Similar results were found regardless of EGFR variation type and brain metastases. The 5-year PFS was 1.71% (95%CI, 0.47-4.54) in the gefitinib group vs 6.67% (95%CI, 3.54-11.15) in the gefitinib plus chemotherapy group, with HR 0.53 (95%CI, 0.42-0.65, p< 0.001). 74.4% in the gefitinib group vs 57.5% in the gefitinib plus chemotherapy group received further therapy. Overall, this update continues to show the outcome benefit of adding chemotherapy to gefitinib in adults with advanced NSCLC harbouring an EGFR mutation.

Image: PD

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