No Benefit With Addition of EGFR Inhibitor to Chemotherapy in Esophageal Cancer

The addition of the EGFR inhibitor panitumumab to cisplatin plus 5-fluorouracil (CF) did not result in an efficacy benefit for patients with advanced esophageal squamous cell cancer (ESCC), according to an interim analysis of an AIO/EORTC trial presented at the ESMO World Congress on Gastrointestinal Cancer 2018.¹

The international, open-label, phase 3 trial randomly assigned 146 patients with nonresectable, advanced, or metastatic ESCC to receive CF (100 mg/m² on day 1 plus 1000 mg/m² per day for days 1 through 4, respectively) with or without panitumumab (9 mg/kg on day 1) until disease progression. The cisplatin dose in the panitumumab combination was reduced to 80 mg/m² due to rates of grade 3/4 serious adverse events (AEs) in the first 60 patients. EGFR and MET protein expression were analyzed using immunohistochemistry for prognostic or predictive status, and serum was collected for enzyme-linked immunosorbent assay analyses.

There was no difference in progression-free survival (PFS) or overall survival (OS) between groups. The median PFS was 5.3 months with panitumumab compared with 5.8 months with CF alone (hazard ratio [HR], 1.21; 95% CI, 0.85-1.73). The median OS was 9.6 months with the EGFR inhibitor–chemotherapy combination compared with 5.8 months with CF (HR, 1.17; 95% CI, 0.79-1.75). Though there was a numeric trend toward improved survival with panitumumab after the cisplatin dose-reduction, it remained nonsignificant compared with CF (9.8 vs 8.3 months, respectively; HR, 0.84; 95% CI, 0.49-1.43).

EGFR and MET protein expression were not associated with clinical outcomes. Prolonged PFS, however, was associated with low serum EGFR levels among all patients (P = .014).

Any AE occurred in 83% and 79% of patients treated with the panitumumab combination or CF, respectively. The most common AEs included diarrhea, hypokalemia, hypomagnesemia, rash, and hand-foot syndrome. The rates of grade 3 or higher AEs were generally similar between groups, but skin reactions occurred more frequently with panitumumab compared with CF only (10% vs 0%).

The authors noted that this was the largest European trial of first-line palliative chemotherapy plus an EGFR inhibitor in patients with ESCC. The results suggest, however, that the addition of an EGFR inhibitor to chemotherapy did not improve outcomes.

Read more of Cancer Therapy Advisor‘s coverage of the ESMO World Congress on Gastrointestinal Cancer 2018 meeting by visiting the conference page.

Reference

1. Moehler M, Maderer A, Thuss-Patience P, et al. Cisplatin/5-fluorouracil +/- panitumumab for patients with nonresectable, advanced, or metastatic esophageal squamous cell cancer: A randomized phase III AIO/EORTC trial with an extensive biomarker program. Ann Oncol. 2018;29 (suppl 5;abstr O-010):v103. doi: 10.1093/annonc/mdy149.009