Chicago, Illinois—Findings from a study presented at the 2019 ASCO Annual Meeting demonstrate first-line therapy with pemetrexed plus carboplatin and gefitinib as a new standard treatment option for patients with EGFR-positive non–small-cell lung cancer (NSCLC).

“Standard first-line therapy for EGFR mutant advanced…NSCLC…is an EGFR-directed oral TKI. We evaluated whether adding pemetrexed-carboplatin to oral TKI would improve outcomes,” explained lead investigator Vanita Noronha, MD, Tata Memorial Centre, Parel, Mumbai, India, and colleagues.

The phase 3 trial by Dr Noronha et al was conducted between August 2016 and August 2018, and included 350 chemotherapy-naïve patients with advanced NSCLC and the EGFR mutation who were randomized in a 1:1 ratio to receive gefitinib 250 mg daily (n = 177) or gefitinib 250 mg daily plus pemetrexed 500 mg/m2 and carboplatin every 3 weeks for 4 cycles, followed by maintenance pemetrexed 500 mg/m2 every 3 weeks (n = 173).

Patients had a median age of 54 years; 48% were women, and 84% had never smoked. Restaging was done every 2 to 3 months, and patients continued to receive therapy until disease progression or intolerable toxicity occurred.

The primary end point of the study was progression-free survival (PFS); secondary end points included overall survival (OS), toxicity and response rate. Dr Noronha and her team used the intention-to-treat population to assess survival end points.

Findings demonstrated a median follow-up in surviving patients of 17 months (range, 7 to 30 months). Radiologic response rates were 81% for recipients of the combination and 69% for recipients of gefitinib alone (P = .012).

Overall, 234 (67%) patients have had events for PFS, including 98 patients in the combination arm and 136 in the gefitinib-alone arm. The estimated median PFS was significantly longer with the combination than with gefitinib alone (16 months; 95% CI, 13.7-18.3] vs 8 months; 95% CI, 7.1-8.9, respectively; hazard ratio for disease progression or death, 0.5; 95% CI, 0.39-0.65; P <.001).

In addition, the estimated median OS was significantly longer with the combination than with gefitinib alone (not reached vs 18 months, respectively; 95% CI, 14.28-21.72; hazard ratio for death, 0.45; 95% CI, 0.31-0.66; P <.001.

According to Dr Noronha et al, 120 (34%) patients have died, including 42 in the combination arm and 78 in the gefitinib-alone arm. Clinically relevant toxicities grade ≥3 occurred in 51% and 25% of patients receiving gefitinib plus carboplatin and gefitinib alone, respectively (P <.001).

“Adding pemetrexed-carboplatin chemotherapy to gefitinib significantly prolonged progression free and overall survival but also increased toxicity,” Dr Noronha and colleagues said.

“Pemetrexed-carboplatin-gefitinib represents a new standard first-line therapy for EGFR mutant NSCLC,” they concluded.—Hina Khaliq

Noronha V, Joshi A, Patil VM, et al. Phase III randomized trial comparing gefitinib to gefitinib with pemetrexed-carboplatin chemotherapy in patients with advanced untreated EGFR mutant non-small cell lung cancer (gef vs gef+C). Presented at: the 2019 ASCO Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 9001.