American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non–Small-Cell Lung Cancer

Abstract

The purpose of this article is to provide updated recommendations for the treatment of patients with stage IV non–small-cell lung cancer. A literature search identified relevant randomized trials published since 2002. The scope of the guideline was narrowed to chemotherapy and biologic therapy. An Update Committee reviewed the literature and made updated recommendations. One hundred sixty-two publications met the inclusion criteria. Recommendations were based on treatment strategies that improve overall survival. Treatments that improve only progression-free survival prompted scrutiny of toxicity and quality of life. For first-line therapy in patients with performance status of 0 or 1, a platinum-based two-drug combination of cytotoxic drugs is recommended. Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy. For patients with performance status of 2, a single cytotoxic drug is sufficient. Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment. Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy. The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor (EGFR) mutation; for negative or unknown EGFR mutation status, cytotoxic chemotherapy is preferred. Bevacizumab is recommended with carboplatin-paclitaxel, except for patients with certain clinical characteristics. Cetuximab is recommended with cisplatin-vinorelbine for patients with EGFR-positive tumors by immunohistochemistry. Docetaxel, erlotinib, gefitinib, or pemetrexed is recommended as second-line therapy. Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib. Data are insufficient to recommend the routine third-line use of cytotoxic drugs. Data are insufficient to recommend routine use of molecular markers to select chemotherapy.

Efficacy and safety of maintenance pemetrexed in patients with advanced nonsquamous non-small cell lung cancer following pemetrexed plus cisplatin induction treatment: A cross-trial comparison of two phase III trials

“…This differential efficacy based on histology, as well as a significant treatment-by-histology interaction for pemetrexed, was consistently detected across multiple studies [6]. These results led to a recommendation of pemetrexed-cisplatin for first-line treatment of patients with advanced nonsquamous NSCLC [2], [3] and [4].…”

“…Platinum-based doublet therapy is recommended for first-line treatment of patients with advanced NSCLC, with cisplatin preferred to carboplatin in Europe [2], [3] and [4]. In a large phase III study of pemetrexed-cisplatin versus gemcitabine-cisplatin, in patients with advanced NSCLC of all histologies (referred to here as "JMDB study"), a pre-specified subgroup analysis in patients with nonsquamous NSCLC showed pemetrexed-cisplatin to have superior survival compared with gemcitabine-cisplatin [5].…”

“…More recently, the PARAMOUNT study examined pemetrexed continuation maintenance therapy following four cycles of pemetrexed-cisplatin as induction treatment and found significantly improved PFS and OS when administered to non-progressing patients with advanced, nonsquamous NSCLC [8] and [9]. Current guidelines recommend maintenance single-agent pemetrexed for patients with stable disease (SD) or tumor response after four cycles of platinum-containing induction therapy [2], [3] and [4].…”

Phase I and II Trials of Vinorelbine With Carboplatin for Patients 75 Years of Age or Older With Previously Untreated Non–Small-Cell Lung Cancer

“…4 Platinum-based chemotherapy is currently recommended as the standard treatment for patients with advanced NSCLC. 5 However, it is unclear whether it should be recommended as the standard regimen for elderly patients with advanced NSCLC. Its efficacy for such a population has been questioned because of the perceived higher risk of toxicity.…”

“…5 On the other hand, large elderly-specific randomized trials have recommended that single-agent chemotherapy with a third-generation agent (e.g., vinorelbine, gemcitabine, taxanes) be used for elderly patients with advanced NSCLC. 5 Vinorelbine is a semisynthetic vinca alkaloid, which showed significantly superior survival over best supportive care (median survival time 27 weeks vs. 21 weeks, p = 0.04) in a landmark Phase III trial in elderly patients with advanced NSCLC. 6 Since then, vinorelbine monotherapy has become one of the most important chemotherapy regimens for elderly patients.…”