Stage IV NSCLC Treatment
The above trials demonstrated that EGFR tyrosine kinase inhibitors such as gefitinib or erlotinib are superior to the platinum combination chemotherapy as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia. It is likely that these results are applicable to non-Asian populations.
- In a European study (EURTAC), 1,227 patients with advanced NSCLC were screened for EGFR mutations. Of these, 174 patients with EGFR mutations were randomly assigned to receive erlotinib or platinum-based chemotherapy. The primary endpoint was PFS.
- In an interim analysis of the first 153 patients, PFS in the chemotherapy arm was 5.2 months (95% CI, 4.5–5.8) compared to 9.7 months (95% CI, 8.4–12.3) in the erlotinib arm (HR, 0.37; P < .0001). Median survival was 19.3 months in the chemotherapy arm and 19.5 months in the erlotinib arm (HR, 0.80; P = .42).[Level of evidence: 1iiDiii]
Maintenance therapy following first-line chemotherapy
One treatment strategy that has been investigated extensively in NSCLC is maintenance therapy following initial response to chemotherapy. Options for maintenance therapy that have been investigated include the following:
- Continuing the initial combination chemotherapy regimen.
- Continuing only single-agent chemotherapy.
- Introducing a new agent as "maintenance."
Multiple randomized trials have evaluated the efficacy of continuing first-line combination cytotoxic chemotherapy beyond three to four cycles.
Evidence (maintenance therapy following first-line chemotherapy):
- None of the trials of continued cytotoxic combinations showed a significant OS advantage with additional or longer durations beyond four cycles.
- Three trials found statistically significantly improved PFS or time to progression with additional chemotherapy.[42,43,44]
- No consistent improvement in quality of life was reported.[43,45,46]
- Chemotherapy-related toxicities were greater with prolonged chemotherapy.[45,46]
These data suggest that PFS, but not OS, may be improved either by continuing an effective chemotherapy beyond four cycles or by immediate initiation of alternative chemotherapy. The improvement in PFS, however, is tempered by an increase in adverse events from additional cytotoxic chemotherapy and no consistent improvement in quality of life. For patients who have stable disease or who respond to first-line therapy, evidence does not support the continuation of cytotoxic chemotherapy until disease progression or the initiation of a different chemotherapy prior to disease progression. Collectively, these trials suggest that first-line cytotoxic combination chemotherapy should be stopped at disease progression or after four cycles in patients whose disease is not responding to treatment; it can be administered for no more than six cycles.[42,43,45,46]