medwireNews: Adjuvant erlotinib significantly prolongs disease-free survival (DFS), compared with a historic benchmark, in patients with epidermal growth factor receptor (EGFR)-mutated stage IA–IIIA non-small-cell lung cancer (NSCLC), US research shows.
Recurrence was rare while patients were receiving the tyrosine kinase inhibitor (TKI), but occurred in 36% after stopping erlotinib, which Nathan Pennell (Cleveland Clinic Taussig Cancer Institute, Ohio) and co-investigators say “calls into question whether adjuvant EGFR TKIs are capable of altering the natural history of the disease to improve cure rates or are merely delaying recurrence.”
The open-label phase II Surgically Resected EGFR-Mutant Lung Cancer With Adjuvant Erlotinib Cancer Treatment (SELECT) trial included 100 patients with resected stage IA–IIIA EGFR-mutant NSCLC who received erlotinib 150 mg daily for 2 years after standard adjuvant chemotherapy with or without radiotherapy.
Almost half (45%) of the patients had stage I disease, while 27% and 28% had stage II and IIIA disease, respectively.
During a median 5.2 years of follow-up, 40 patients experienced disease recurrence, at a median 25.4 months after stopping erlotinib, with only four recurrences occurring during erlotinib treatment.
The primary endpoint of 2-year DFS was 88%, which was significantly greater than the historic control rate of 76%, derived from a Memorial Sloan Kettering Cancer Center cohort.
The 2-year DFS rate was 96% for patients with stage I disease, 78% for those with stage II disease, and 91% for those with stage IIIA disease.
Median DFS and overall survival (OS) have not yet been reached, but 5-year DFS was 56% and 5-year OS was 86%, Pennell and co-authors report in the Journal of Clinical Oncology.
The researchers note that only one of the 24 patients with recurrence who underwent repeat biopsy had acquired a T790M mutation. This patient had progressed while still receiving erlotinib, suggesting that the underlying cause for recurrence among the remaining patients “was stopping the suppressive erlotinib rather than truly acquiring resistance to erlotinib,” Pennell et al remark.
They say that adverse events were “typical of erlotinib,” and were no more severe than grade 3. However, the team points out that while the majority (69%) of patients completed treatment, “dose reductions were still required in 40% of patients, and an additional 11% stopped treatment shortly after starting because of intolerance, suggesting that toxicity is likely to be a significant issue in any adjuvant trial using first-generation EGFR TKIs.”
Nonetheless, Pennell and colleagues conclude: “The 2-year DFS of 88% in the SELECT trial is promising and exceeds that of a large retrospective cohort of patients with resected early-stage EGFR-mutant NSCLC who received no adjuvant EGFR TKI.”
They add: “Ongoing and future randomized trials will formally define the clinical benefit of adjuvant EGFR TKIs in this setting.”
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group