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Pemetrexed and Carboplatin Plus TKI in Advanced EGFR-Mutant Lung Cancer

By: Joseph Fanelli
Posted: Monday, January 20, 2020

According to findings presented in the Journal of Clinical Oncology, adding pemetrexed and carboplatin chemotherapy to the oral tyrosine kinase inhibitor (TKI) gefitinib may improve progression-free and overall survival in the first line for patients with advanced EGFR-mutant non–small cell lung cancer (NSCLC). However, Vanita Noronha, MBBS, MD, DM, of the Tata Memorial Center, Mumbai, India, and colleagues noted that the combination therapy was associated with an increase in toxicity.

In this Indian, single-center, phase III trial, the investigators enrolled 350 patients with advanced NSCLC who had an EGFR-sensitizing mutation and a performance status of 0 to 2 who planned to receive first-line palliative therapy. Of the patients, 176 received 250 mg of gefitinib daily. The other 174 patients received the same dose of gefitinib plus 500 mg/m2 of pemetrexed and carboplatin at AUC 5 every 3 weeks for 4 cycles, followed by maintenance pemetrexed. Of the patients , 18% had brain metastases.

After a median follow-up of 17 months, patients treated with gefitinib alone had a radiologic response rate of 63%, whereas for those treated with gefitinib and carboplatin, it was 75%. The estimated median progression-free survival for patients treated with gefitinib and carboplatin was “significantly longer” than for those treated with gefitinib alone (16 months vs. 8 months).

Patients treated with gefitinib and carboplatin also recorded a longer estimated median overall survival time (not reached) than patients in the gefitinib-alone arm (17 months). Those treated with gefitinib and carboplatin, though, experienced clinically relevant grade 3 or greater toxicities at a higher rate (51% vs. 25%, respectively). Hematologic toxicity (anemia, neutropenia, and febrile neutropenia), nephrotoxicity, and hypokalemia occurred more often with the combination therapy than gefitinib alone.

Disclosure: For full disclosures of the study authors, visit jco.ascopubs.org.



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