Adjuvant therapy in non-small cell lung cancer: current and future directions

Abstract

The cornerstone of treatment for early-stage non-small cell lung cancer (NSCLC) has long been surgical resection. Over the past few years, there has been a paradigm shift to provide adjuvant platinum-based chemotherapy for patients with completely resected stage II-IIIA NSCLC founded on large randomized clinical trials demonstrating longer overall survival with this treatment. Reassuringly, the National Cancer Institute of Canada Cancer Therapeutics Group JBR.10 trial recently reported a continued survival advantage for patients treated with adjuvant chemotherapy after >9 years of median follow-up. In contrast, the gains from using this approach for stage IB disease are less clear, although data from an unplanned subgroup analysis suggest benefit for patients with tumors > or = 4 cm. Herein, we review the evidence supporting adjuvant therapy in early-stage NSCLC patients before discussing key mitigating factors in providing treatment, such as stage of disease and the impact of the new seventh edition of the tumor-node-metastasis classification system. Criteria such as patient age and performance status, as well as the value of appropriate chemotherapy selection, are highlighted as measures to help guide management. The role of postoperative radiotherapy and the future landscape of early-stage NSCLC research are also explored; namely, therapeutic strategies exploiting pharmacogenomic and gene-expression profiling, in an attempt to personalize care, and the integration of novel targeted therapies into adjuvant clinical trials.

Figure 1.

ECOG 1505: Phase III trial of adjuvant chemotherapy with or without bevacizumab for completely resected stage IB–IIIA NSCLC. Abbreviations: DFS, disease-free survival; ECOG, Eastern Cooperative Oncology Group; NSCLC, non-small cell lung cancer; OS, overall survival; PS, performance status; q21, every 21.

Figure 2.

RADIANT: Phase III trial of adjuvant erlotinib after surgical resection of stage IB–IIIA EGFR⁺ NSCLC. Abbreviations: DFS, disease-free survival; EGFR, epidermal growth factor receptor; FISH, fluorescent in situ hybridization; IHC, immunohistochemistry; NSCLC, non-small cell lung cancer; OS, overall survival; RADIANT, Randomized Double-Blind Trial in Adjuvant NSCLC with Tarceva®.