Addition of Pemetrexed and Carboplatin to Gefitinib Doubled PFS in Patients with EGFR-Mutant NSCLC

On behalf of derived outcomes of a randomized phase 3 study came into view in the Journal of Clinical Oncology, adding pemetrexed and carboplatin to gefitinib significantly enhanced the progression free survival and OS for participants with NSCLC and EGFR-sensitizing mutations. 

Although data suggests that the clinically relevant severe toxicities have been observed twice as often with the combination regimen than with gefitinib alone.

According to Vanita Noronha, MD, MBBS, professor in the department of medical oncology at Tata Memorial Hospital in Mumbai, India, and colleagues, “Apart from the detection of molecular target and using medications, believed to bind to the target, cure and long-term remission elude us,” “Resistance inevitably occurs within 8-12 months. Number of ways have been implemented in order to reduce the emergence of resistance. One strategy involved in order to combine the cytotoxic chemotherapy with an EGFR TKI.” She added. 

Between August 2016 and August 2018, in an open-label study conducted by Noronha and colleagues, total 350 participants enrolled with advanced, chemotherapy-naive, EGFR-mutated Non-Small Cell Lung Cancer. About 18% of participants had brain metastases and 21% found with an ECOG performance status of 2.

The investigators differentiated patients on the basis of performance status and EGFR mutation type and randomly assigned them 1:1 to gefitinib 250 mg orally once per day alone (n = 176; median age, 56 years; range, 27-78) or with pemetrexed 500 mg/m2 IV and carboplatin IV area under the curve 5 each 3 weeks for the four cycles (n =174; median age, 54 years; range, 27-75). The combination regimen was followed by maintenance pemetrexed 500 mg/m2 IV every three weeks.

The progression free survival represents as the primary endpoint, and OS, toxicity and RR represent as the secondary endpoints. The researchers specified survival endpoints in the intention in order to treat the population. The median follow-up reported about 17 months.

About 80% of participants treated with gefitinib and chemotherapy, completed all four cycles of pemetrexed and carboplatin. Outcomes represented ORR of about 75.3% among participants in the combination population and 62.5% in the gefitinib-only population. Participants in the combination population had longer median progression free survival than those in the gefitinib-only population. The combination population had significantly longer median overall survival than the gefitinib population.

About 50% of patients in the combination population experienced grade 3 or higher toxicities; maximum because of the chemo induced myelosuppression and nephrotoxicity, compared with 25.3% of those in the gefitinib population.

Researchers have written, “Adding pemetrexed and carboplatin to gefitinib prolonged PFS (progression free survival) and overall survival, but also be responsible for increasing the toxicity."

Also, Jennifer Byrne stated that, "The pemetrexed, carboplatin and gefitinib, together appeared as a new standard first-line therapy for patients with the EGFR-mutant Non-Small Cell Lung Cancer.”