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Frontline Icotinib Improves PFS Versus Chemo in EGFR+ NSCLC

Jason Harris
Published: Wednesday, Sep 06, 2017

lung cancer
Icotinib (Conmana) was associated with a 3.3-month increase in median progression-free survival (PFS) compared with chemotherapy in patients with stage IIIB/IV non–small cell lung cancer (NSCLC) in the phase III Chinese CONVINCE trial.

As assessed by an independent response evaluation committee, PFS was 11.2 months for treatment-naïve patients assigned to icotinib compared with 7.9 months for those treated with chemotherapy (hazard ratio [HR], 0.61; 95% CI, 0.43-0.87; P = .006).

Investigator-assessed median PFS results were similar (9.9 months vs 7.3 months; HR, 0.65; 95% CI, 0.48-0.88; P = .005).

Investigators observed no significant difference between treatment groups for PFS or overall survival (OS) in either the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R).

“To the best of our knowledge, this study provides the first direct evidence for the superiority of icotinib over first-line cisplatin/pemetrexed plus pemetrexed maintenance in untreated patients with EGFR mutation-positive lung adenocarcinoma,” the Chinese research team wrote. “Icotinib conferred a significant PFS advantage assessed by both [the by independent response evaluation committee] and investigators, along with a better safety profile, compared with first-line chemotherapy.”

To assess the efficacy and safety of icotinib, a highly selective oral tyrosine kinase inhibitor, a team of Chinese investigators lead by Yuankai Shi, MD, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, recruited 296 patients at 18 sites in China into CONVINCE, an open-label, randomized, phase III trial. Eleven patients in the chemotherapy arm did not receive treatment, so the safety and efficacy data included a total of 285 patients.

Patients were randomly assigned to receive 125 mg of oral icotinib (n = 148) 3 times daily or 3-week cycles of 75 mg/m2 of cisplatin plus 500 mg/m2 of pemetrexed on day 1 for up to 4 cycles (n = 137). Patients with nonprogressive disease after 4 cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary endpoint was PFS as determined by independent response evaluation committee. Secondary endpoints included OS and safety.

Neither physicians nor patients were masked to treatment assignment. Postprogression crossover was at the physician’s discretion.

The median duration of follow-up for PFS was 18.0 months in the icotinib arm and 15.7 months in the chemotherapy arm. Median duration of follow-up for OS was 39.6 months for both groups.

Patients with brain metastasis (27.7%) had a lower OS compared to patients without brain metastasis, irrespective of treatment, but the difference was not statistically significant. In a multivariable analysis of OS, clinical factors—including, ECOG PS, gender, smoking status, mutation type, and disease stage—were not predictors for OS.

Median duration of treatment was 10.0 months for the icotinib group and 7 cycles for the chemotherapy group. The average dose intensity for cisplatin was 24.3 mg/m2 per week and 164.9 mg/m2 per week for pemetrexed.

Dose reductions of chemotherapy were done if necessary. Dose reductions of icotinib were not recommended, but treatment was allowed to be interrupted for up to 14 days if grade 3 or 4 adverse events (AEs) were observed. Patients were withdrawn from the study if the AEs were not recovered to grade 1 or 2 after treatment interruption.

Patients assigned to chemotherapy were more than twice as likely to experience grade 3/4 AEs (24.8% vs 9.5% with icotinib; P = .001). In the icotinib arm, the most common grade 3/4 AEs (≥5%) were rash (14.9%) and diarrhea (7.4%). In comparison, the most common grade 3/4 AEs (≥20%) in the chemotherapy arm were nausea (46.0%), vomiting (29.2%), and decreased appetite (23.4%).

Patients in the chemotherapy group were also more likely to experience treatment-related grade 3/4 AEs (23.4% vs 4.7% with icotinib; P <.001). Those patients were also more than 8 times more likely to require drug discontinuation due to AEs (17.5% vs 2%).
Shi YK, Wang L, Han BH, et al. First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study [published online August 23, 2017]. Ann Oncol. doi: 10.1093/annonc/mdx359.



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