medwireNews: The CTONG-1103 EMERGING trial investigators believe that neoadjuvant treatment with epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR–TKIs) for stage IIIA-N2 non-small-cell lung cancer (NSCLC) warrants further investigation.
They compared neoadjuvant erlotinib with gemcitabine plus cisplatin in Chinese patients with treatment-naïve disease harboring an activating EGFR mutation, and found that outcomes were better with the EGFR–TKI.
Participants of the phase II trial were randomly assigned to receive either erlotinib 150 mg/day for 42 days prior to surgery or two 3-week cycles of gemcitabine 1250 mg/m2 (on days 1 and 8) and cisplatin 75 mg/m2 (on day 1). After surgery, the patients continued their treatment as per the random assignment, with the only difference being that adjuvant erlotinib was given for 12 months.
As reported at the ESMO 2018 Congress in Munich, Germany, the primary endpoint of objective response rate was higher for the 37 participants who received erlotinib than for the 35 patients treated with gemcitabine plus cisplatin, at 54.1% versus 34.3%. However, the difference was not statistically significant.
With regard to the secondary endpoints, there were no pathologic complete responses in either arm, but the rate of major pathologic response – defined as less than 10% viable tumor cells surviving – was higher in the erlotinib than chemotherapy group, at 10.7% and 0.0%, respectively.
And progression-free survival was significantly improved with erlotinib relative to chemotherapy, with corresponding median durations of 21.5 and 11.9 months, and a hazard ratio for progression or death of 0.42 favoring the EGFR–TKI.
A numerically higher proportion of erlotinib-treated patients than their counterparts given chemotherapy proceeded to surgery (83.8 vs 68.6%), had a complete resection (73.0 vs 62.9%), and achieved lymph node downstaging (10.8 vs 2.9%), but none of these differences reached statistical significance.
Presenting author Wen-Zhao Zhong, from Guangdong General Hospital in Guangzhou, China, noted that the postoperative complications were balanced across the treatment groups, “very mild,” and consistent with other studies. And there was no perioperative mortality in either group.
The neoadjuvant safety profile in terms of any-grade and grade 3 or 4 adverse events favored erlotinib over chemotherapy, Zhong added, with corresponding rates of 75.7% versus 88.2% and 0.0% versus 29.4%, respectively.
Noting the difficulties associated with conducting neoadjuvant trials, such as the need for additional biopsy and the potential for missing the window of surgery, discussant Suresh Ramalingam (Winship Cancer Institute of Emory University, Atlanta, Georgia, USA) commended the CTONG-1103 EMERGING researchers for addressing this important clinical question.
However, he pointed out that the rates of response and nodal downstaging were lower than expected in both study arms, and added that the treatment effect of erlotinib appeared to be less than that seen in stage IV EGFR-mutated NSCLC.
As such, Ramalingam concluded that neoadjuvant EGFR–TKI therapy in stage III-N2 disease “is not ready for center-stage.”
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