Randomized Phase II Trial of Gefitinib With and Without Pemetrexed as First-Line Therapy in Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations

Abstract

P+G improved PFS compared with gefitinib alone in East Asian patients with advanced NS NSCLC and activating EGFR mutations. This combination may offer EGFR mutation-positive patients new treatment options and improved clinical outcomes compared with the current standard of care.

EGFR inhibition in NSCLC: New findings…. and opened questions?

“…The study met its primary end-point in the intent-to-treat population, showing a significantly longer median PFS in favour of the combination arm (15.8 vs 10.9 months; HR: 0.68; 95%CI: 0.48--0.96), independently from the specific type of mutation (EGFR exon 19 deletion vs L858R mutation), while no differences in response rate (RR: 80% vs 74%) were observed between the two treatment arms. As attended, the percentage of patients who reported G3-4 drug-related AEs was significantly higher (42% vs 19%) in the combination arm as well as the proportion of patients who discontinued treatment (Cheng et al, 2016). Similarly the NEJ005 randomized phase II study, prospectively compared concurrent gefitinib plus carboplatin/pemetrexed regimen vs sequential alternating regimen in East-Asian, EGFR-mutated NSCLC patients.…”

Adding chemotherapy to TKI: can we improve first-line treatment for EGFR-mutated NSCLC patients?

“…In The Journal of Clinical Oncology, Ying Cheng and colleagues (1) have recently reported the results of a phase II randomized trial comparing pemetrexed plus gefitinib vs. gefitinib in treatment-naive, East Asian patients, with advanced non-squamous non-small cell lung cancer (NSCLC) and activating epidermal growth factor receptor (EGFR) mutations. The study met its primary end-point in the intent-to-treat population, showing a significantly longer median progression free survival (PFS) in favors of the combination arm (15.8 months) compared to single agent arm (10.9 months) [hazard ratio (HR): 0.68; 95% CI, 0.48 to 0.96; one-sided P=0.014; two-sided P=0.029].…”

Gefitinib with pemetrexed as first-line therapy in patients with advanced nonsquamous non-small cell lung cancer with activating epidermal growth factor receptor mutations

“…So the enhancement of cytotoxicity when pemetrexed is added to gefitinib might suppress the small subpopulation of cells harboring T790M mutation or with the mesenchymal phenotype. Preclinical studies indicated there is cell cycle dependent synergism or antagonism when combining chemotherapy and EGFR TKI, however clinical data do not support it well (10)(11)(12)(13)(14)(15)(16).…”

“…Interestingly, two PFS curves run along initially then began to divert after more than 6 months later of treatment, which suggests that the PFS prolonging effect would be attributed to the suppression of resistant clones by the addition of concurrent pemetrexed. Continuous treatment with pemetrexed might have produced different results rather than combining up to six cycles of chemotherapy in CALGB 30406 trial (13,14).…”

“…In the study led by Cheng et al they added concomitant pemetrexed to gefitinib in the patients with EGFR mutated tumor and showed PFS of 15.8 months (95% CI, 12.6-18.3) compared with 10.9 months [95% CI, 9.7-13.8, adjusted hazard ratio 0.68 (95% CI, 0.48-0.96)] with gefitinib alone (P=0.14) (14). The result was regardless of the mutational type (exon 19 deletion or L858R point mutation).…”