Forty percent of patients with newly diagnosed NSCLC have stage IV disease. Treatment goals are to prolong survival and control disease-related symptoms. Treatment options include cytotoxic chemotherapy and targeted agents. Factors influencing treatment selection include comorbidity, performance status (PS), histology, and molecular genetic features of the cancer. Radiation therapy and surgery are generally used in selective cases for symptom palliation.
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Randomized controlled trials of patients with stage IV disease and good PS have shown that cisplatin-based chemotherapy improves survival and palliates disease-related symptoms.[Level of evidence: 1iiA] Patients with nonsquamous cell histology, good PS, no history of hemoptysis or other bleeding, or recent history of cardiovascular events may benefit from the addition of bevacizumab to paclitaxel and carboplatin. Patients with tumors harboring mutations in EGFR, particularly those from East Asia, never smokers, and those with adenocarcinoma may benefit from EGFR tyrosine kinase inhibitors as an alternative to first- or second-line chemotherapy. Second-line chemotherapy with docetaxel, pemetrexed, or erlotinib also improves survival in patients with good PS.[Level of evidence: 1iiA] The role of chemotherapy in patients with poor PS was less certain.
Cytotoxic combination chemotherapy
The type and number of chemotherapy drugs to be used for the treatment of patients with advanced NSCLC has been extensively evaluated in randomized controlled trials and meta-analyses.
Several randomized trials have evaluated various drugs combined with either cisplatin or carboplatinum in previously untreated patients with advanced NSCLC. Based on meta-analyses of the trials, the following conclusions can be drawn:
Certain three-drug combinations that add so-called targeted agents may result in superior survival.
EGFR inhibitors may benefit selected patients with EGFR mutations.
Maintenance chemotherapy following four cycles of platinum combination chemotherapy may improve progression-free survival (PFS).
Platinum combinations with vinorelbine, paclitaxel, docetaxel, gemcitabine, irinotecan, and pemetrexed yield similar improvements in survival. Types and frequencies of toxic effects differ, and these may determine the preferred regimen for an individual patient. Patients with adenocarcinoma may benefit from pemetrexed.
Cisplatin and carboplatinum yield similar improvements in outcome with different toxic effects. Some, but not all, trials and meta-analyses of trials suggest that outcomes with cisplatin may be superior, although with a higher risk of certain toxicities such as nausea and vomiting.
Nonplatinum combinations offer no advantage to platinum-based chemotherapy, and some studies demonstrate inferiority.
Three-drug combinations of the commonly used chemotherapy drugs do not result in superior survival and are more toxic than two-drug combinations.