Adding cetuximab to afatinib not beneficial in treatment-naïve EGFR-mutant NSCLC

Christina Lau
05 Oct 2018
Adding cetuximab to afatinib not beneficial in treatment-naïve EGFR-mutant NSCLC

Adding cetuximab to afatinib does not improve overall survival (OS), progression-free survival (PFS) or objective response rate (ORR) in the first-line treatment of patients with advanced or recurrent non-small-cell lung cancer (NSCLC) harbouring classical sensitizing EGFR mutations.

The results, from the Southwest Oncology Group (SWOG) S1403 trial reported at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer (WCLC 2018), also confirm clinical suspicion of excessive overlapping toxicity with the cetuximab/afatinib combination. [Goldberg SB, et al, WCLC 2018, abstract OA10.04]

In the phase II trial, 170 patients with recurrent or advanced NSCLC who had EGFR exon 19 deletion or L858R mutation were randomized in a 1:1 ratio to receive first-line treatment with afatinib (40 mg daily) with or without cetuximab (500 mg/m2 Q2W).

“The primary endpoint of PFS did not differ significantly between patients who received combination therapy and those who received afatinib monotherapy,” reported investigator Dr Sarah Goldberg of Yale University, New Haven, Connecticut, US.

Median PFS was 13.1 months in the monotherapy arm compared with 10.6 months in the combination therapy arm (hazard ratio [HR], 1.17; 95 percent confidence interval [CI], 0.80 to 1.73; p=0.42).

“Similarly, no OS benefit was observed with the addition of cetuximab to afatinib. Median OS was not reached in the afatinib monotherapy arm vs 26.9 months in the cetuximab/afatinib arm [HR, 1.23; 95 percent CI, 0.62 to 2.44; p=0.55],” said Goldberg.

“ORR was 68 percent with afatinib monotherapy compared with 58 percent with cetuximab/afatinib combination therapy [p=0.22]. Time to treatment discontinuation was 12.2 months vs 12.5 months [HR, 0.95; 95 percent CI, 0.64 to 1.39; p=0.79],” she continued.

The addition of cetuximab to afatinib resulted in a substantial increase in grade ≥3 treatment-related adverse events (AEs) (61.7 percent vs 39.3 percent with afatinib monotherapy).

“Interestingly, grade 2 diarrhoea was more common with combination therapy [30.9 percent vs 22.6 percent with monotherapy], but grade ≥3 diarrhoea was more common in the monotherapy arm [20.2 percent vs 11.1 percent with combination therapy],” noted Goldberg.

Rash of grade 1 was more commonly reported in the monotherapy vs combination therapy arm (71.4 percent vs 29.6 percent). However, rates of grade 2 and grade ≥3 rash were higher in the combination therapy arm (61.7 percent vs 22.6 percent and 37 percent vs 2.4 percent, respectively).

“Rates of oral mucositis and paronychia were generally similar between the two arms,” said Goldberg.

“Because of increased toxicity, more patients in the combination therapy arm required dose reduction of afatinib to 30 mg or 20 mg [56.7 percent vs 26.2 percent and 24.7 percent vs N/A, respectively]. About 25 percent of patients in the combination therapy arm discontinued cetixumab while remaining on afatinib,” she noted. “This may explain the lack of benefit with the cetuximab/afatinib combination observed in our trial.”

The proportion of patients who discontinued treatment due to AEs was, however, similar between the combination therapy and monotherapy arms (11.6 percent vs 10.7 percent).

The trial was originally designed to evaluate OS as a primary endpoint with an accrual goal of 605 patients. “Due to slow accrual and the approval of osimertinib during the trial, the design was modified to evaluate PFS as a primary endpoint with an accrual goal of 212 patients,” said Goldberg.

Editor's Recommendations
Related Diseases