Table 1.

Summary of Recommendations

Recommendation No.	Recommendation
First-line chemotherapy
A1	Evidence supports the use of chemotherapy in patients with stage IV NSCLC with ECOG/Zubrod performance status of 0, 1, and possibly 2.
A2	In patients with performance status of 0 or 1, evidence supports using a combination of two cytotoxic drugs for first-line therapy. Platinum combinations are preferred over nonplatinum combinations because they are superior in response rate, and marginally superior in overall survival. Nonplatinum therapy combinations are a reasonable in patients who have contraindications to platinum therapy. Recommendations A8 and A9 address whether to add bevacizumab or cetuximab to first-line cytotoxic therapy.
A3	Available data support the use of single-agent chemotherapy in patients with performance status of 2. Data are insufficient to make a recommendation for or against using a combination of two cytotoxic drugs in patients with performance status of 2.
A4	The evidence does not support the selection of a specific first-line chemotherapy drug or combination based on age alone.
A5	The choice of either cisplatin or carboplatin is acceptable. Drugs that may be combined with platinum include the third-generation cytotoxic drugs docetaxel, gemcitabine, irinotecan, paclitaxel, pemetrexed, and vinorelbine. The evidence suggests that cisplatin combinations have a higher response rate than carboplatin and may improve survival when combined with third-generation agents. Carboplatin is less likely to cause nausea, nephrotoxicity, and neurotoxicity than cisplatin but more likely to cause thrombocytopenia.
A6	In patients with stage IV NSCLC, first-line cytotoxic chemotherapy should be stopped at disease progression or after four cycles in patients whose disease is stable but not responding to treatment. Two-drug cytotoxic combinations should be administered for no more than six cycles. For patients with stable disease or response after four cycles, immediate treatment with an alternative, single-agent chemotherapy such as pemetrexed in patients with nonsquamous histology, docetaxel in unselected patients, or erlotinib in unselected patients may be considered. Limitations of these data are such that a break from cytotoxic chemotherapy after a fixed course is also acceptable, with initiation of second-line chemotherapy at disease progression.
A7	In unselected patients, erlotinib or gefitinib should not be used in combination with cytotoxic chemotherapy as first-line therapy. In unselected patients, evidence is insufficient to recommend single-agent erlotinib or gefitinib as first-line therapy. First-line use of gefitinib may be recommended for patients with activating EGFR mutations. If EGFR mutation status is negative or unknown, then cytotoxic chemotherapy is preferred (see Recommendation A2).
A8	Based on the results of one large phase III randomized controlled trial, the Update Committee recommends the addition of bevacizumab, 15 mg/kg every 3 weeks, to carboplatin/paclitaxel, except for patients with squamous cell carcinoma histologic type, brain metastases, clinically significant hemoptysis, inadequate organ function, ECOG performance status > 1, therapeutic anticoagulation, clinically significant cardiovascular disease, or medically uncontrolled hypertension. Bevacizumab may be continued, as tolerated, until disease progression.
A9	On the basis of the results of one large phase III randomized controlled trial, clinicians may consider the addition of cetuximab to cisplatin/vinorelbine in first-line therapy in patients with EGFR-positive tumor as measured by immunohistochemistry. Cetuximab may be continued, as tolerated, until disease progression.
Second-line chemotherapy
B1	Docetaxel, erlotinib, gefitinib, or pemetrexed is acceptable as second-line therapy for patients with advanced NSCLC with adequate performance status when disease has progressed during or after first-line, platinum-based therapy.
B2	The evidence does not support the selection of a specific second-line chemotherapy drug or combination based on age alone.
Third-line chemotherapy
C1	When disease progresses during or after second-line chemotherapy, treatment with erlotinib may be recommended as third-line therapy for patients with performance status of 0 to 3 who have not received prior erlotinib or gefitinib.
C2	The data are not sufficient to make a recommendation for or against using a cytotoxic drug as third-line therapy. These patients should consider experimental treatment, clinical trials, and best supportive care.
Molecular analysis
D1	Evidence is insufficient to recommend routine use of molecular markers* to select systemic treatment in patients with metastatic NSCLC.
D2	In order to obtain tissue for more accurate histologic classification or for investigational purposes, Update Committee supports reasonable efforts to obtain more tissue than what is contained in a routine cytology specimen.

NOTE. Bold font indicates changes in 2011 Focused Update.¹

Abbreviations: ECOG, Eastern Cooperative Oncology Group; EGFR, epidermal growth factor receptor; NSCLC, non–small-cell lung cancer; TKI, tyrosine kinase inhibitor.

^*In April 2011, the American Society of Clinical Oncology issued Provisional Clinical Opinion regarding EGFR testing. It will be incorporated into future updates of NSCLC guideline: On the basis of the results of five phase III randomized controlled trials, patients with NSCLC who are being considered for first-line therapy with EGFR TKI (patients who have not previously received chemotherapy or EGFR TKI) should have their tumor tested for EGFR mutations to determine whether EGFR TKI or chemotherapy is the appropriate first-line therapy (http://www.asco.org/pco/egfr).