medwireNews: Phase III study results suggest gefitinib in combination with chemotherapy improves outcomes versus gefitinib alone in patients with EGFR-mutated, advanced non-small-cell lung cancer (NSCLC).
This improvement was accompanied by “an acceptable safety profile” and a comparable quality of life to that seen with single-agent gefitinib, say Akira Inoue (Tohoku University School of Medicine, Sendai, Japan) and fellow NEJ009 investigators.
They add that these results, published in the Journal of Clinical Oncology, reinforce the previously reported findings from an Indian trial investigating this combination also in patients with stage IIIB or IV NSCLC.
In the current trial, the 170 patients receiving the combination treatment – gefitinib 250 mg daily together with up to six 3-week cycles of carboplatin area under the curve 5 and pemetrexed 500 mg/m2, followed by gefitinib and pemetrexed maintenance – had a significantly better median PFS than those given gefitinib monotherapy, at 20.9 versus 11.2 months, equating to a hazard ratio for progression or death of 0.49.
Combination treatment was also associated with significantly improved overall survival (OS) relative to the tyrosine kinase inhibitor (TKI) alone, with median durations of 50.9 and 38.8 months, respectively, and the objective response rate was significantly higher as well, at 84% versus 67%.
The researchers urge caution, however, as according to the statistical plan of the trial, OS “should not [have undergone] hierarchical testing” following a nonsignificant PFS2 result. They therefore note that the OS benefit of the combination regimen “requires further validation.”
The patients who received combination treatment had a higher incidence of grade 3 or above adverse events, at a rate of 65.3% compared with 31.0% for gefitinib-treated participants. But even though there was a treatment-related death within the combination group, the researchers did not observe a significant difference in the incidence of adverse event-related treatment discontinuation between patients who received chemotherapy with gefitinib and those who did not.
Moreover, global quality of life scores, as assessed by the EORTC QLQ-C30, were comparable across the combination and gefitinib alone groups at all timepoints from 6 to 36 months; the only exception was the 8-week assessment at which time combination-treated patients reported worse scores than their monotherapy-treated counterparts.
Inoue et al warn, however, that a greater proportion of the combination group than the monotherapy group completed the questionnaire, “which indicates that informative censoring occurred in the gefitinib group more because of poorer prognosis.”
The team concludes: “Since TKIs cannot cure metastatic NSCLC, cytotoxic chemotherapy still plays an important role in anticancer treatment, and a strategy that uses […] multiple effective agents should be investigated further.
“In this point of view, we are now conducting a randomized phase II study […] that compares a combination of osimertinib and carboplatin plus pemetrexed with osimertinib alone for patients with EGFR-mutated, T790M-positive NSCLC as well as planning a study of the same combination as first-line treatment.”
By Hannah Kitt
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J Clin Oncol 2019; doi:10.1200/JCO.19.01488