Adding Pemetrexed To Gefitinib May Boost Nonsquamous NSCLC PFS

Gefitinib plus pemetrexed may be an effective combination for patients with advanced non-small-cell lung cancer positive for an epidermal growth factor receptor mutation

medwireNews: Combining gefitinib with pemetrexed improves progression-free survival (PFS) in advanced nonsquamous non-small-cell lung cancer (NSCLC), suggest the results of a phase II trial in East Asian patients.

The chemotherapy-naive patients from China, Japan, Korea and Taiwan all had disease positive for epidermal growth factor receptor (EGFR) mutations and were randomly assigned to receive open-label gefitinib (250 mg/day) alone or alongside pemetrexed (500 mg/m2 on day 1 of a 21-day cycle).

The 129 patients given the EGFR tyrosine kinase inhibitor (TKI) gefitinib plus the folate antimetabolite pemetrexed had significantly longer PFS than those given only gefitinib, at a median of 15.8 versus 10.9 months and an adjusted hazard ratio of 0.68.

Unadjusted subgroup analysis showed this significant gain in PFS with combined therapy also occurred in many subgroups, including patients with an EGFR exon 19 deletion (HR=0.67) and those with an exon 21 L858R point mutation (HR=0.58).

PFS was also significantly longer with gefitinib plus pemetrexed in nonsmokers (HR=0.58), patients aged less than 65 years and older individuals (HR=0.75 and 0.61), and patients who had not previously received adjuvant or neoadjuvant chemotherapy (HR=0.70). The researchers note that overall survival data have not yet matured.

Patients given combined therapy were significantly more likely to experience at least one grade 3 or 4 treatment-emergent adverse event than those given only gefitinib (42 vs 19%) and more likely to interrupt treatment for adverse events (33 vs 15%).

But the researchers say the “toxicities were clinically manageable” and patients given gefitinib plus pemetrexed were not significantly more likely to discontinue treatment for serious or nonserious side effects than those given gefitinib alone.

“These results suggest that patients with [nonsquamous] NSCLC with activating EGFR mutations may obtain clinical benefit from the addition of pemetrexed to EGFR-TKIs”, the team concludes in the Journal of Clinical Oncology.

“If the combination of pemetrexed plus EGFR-TKI is used in the first-line setting, platinum-based therapies may still be used after progression”, they write.

“The combination of pemetrexed and an EGFR-TKI may be a new treatment option for patients with EGFR mutation–positive [nonsquamous] NSCLC that could improve clinical outcomes compared with the current standard of care.”


Cheng Y, Murakami H, Yang P-C, et al. 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. J Clin Oncol 2016; Advance online publication 9 August. doi: 10.1200/JCO.2016.66.9218

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