What are the benefits of erlotinib combined therapies for the treatment of non–small cell lung cancer (NSCLC)?

Updated: Jul 15, 2021
  • Author: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
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Similar to the experience with gefitinib, no benefit was seen when erlotinib was combined with chemotherapy. Earlier studies also showed better response rates and survival with females, Asian persons, nonsmokers, particularly those with adenocarcinoma histology (especially bronchioalveolar cancer), as was seen with gefitinib.

In contrast, a study in 760 unselected patients with advanced NSCLC found that first-line treatment with erlotinib followed at disease progression by cisplatin-gemcitabine was significantly inferior in terms of overall survival compared with the standard sequence of chemotherapy with cisplatin-gemcitabine followed by erlotinib. [159]

A study by Herbst et al found no benefit when erlotinib was combined with bevacizumab compared with erlotinib alone in patients who experienced a failure of standard first-line chemotherapy. [160] A separate study by Hirsch et al compared the use of erlotinib alone or intercalated with chemotherapy among chemotherapy-naïve patients with advanced NSCLC who were positive for EGFR protein expression, had a high EGFR gene copy number, or both. The study results did not support combined chemotherapy and erlotinib in this setting; patients with tumors harboring EGFR mutations had better outcomes with erlotinib alone. [161]

In contrast, the phase III RELAY trial demonstrated a benefit when erlotinib was combined with ramucirumab for metastatic NSCLC in treatment-naïve patients (n=449) whose tumors have EGFR exon 19 deletion or exon 21 L858R mutations. In RELAY, patients who received erlotinib plus ramucirumab had a significantly longer median progression-free survival compared with those who received erlotinib plus placebo (19.4 months vs. 12.4 months, respectively; hazard ratio [HR] 0.59; 95% CI, 0.46-0.79). [162] On the basis of the RELAY trial results, the FDA approved ramucirumab in combination with erlotinib for first-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations.

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