Maintaining clarity: Review of maintenance therapy in non-small cell lung cancer

Abstract

The purpose of this article is to review the role of maintenance therapy in the treatment of advanced non-small cell lung cancer (NSCLC). A brief overview about induction chemotherapy and its primary function in NSCLC is provided to address the basis of maintenance therapies foundation. The development of how maintenance therapy is utilized in this population is discussed and current guidelines for maintenance therapy are reviewed. Benefits and potential pitfalls of maintenance therapy are addressed, allowing a comprehensive review of the achieved clinical benefit that maintenance therapy may or may not have on NSCLC patient population. A review of current literature was conducted and a table is provided comparing the results of various maintenance therapy clinical trials. The table includes geographical location of each study, the number of patients enrolled, progression free survival and overall survival statistics, post-treatment regimens and if molecular testing was conducted. The role of molecular testing in relation to therapeutic treatment options for advanced NSCLC patients is discussed. A treatment algorithm clearly depicts first line and second line treatment for management of NSCLC and includes molecular testing, maintenance therapy and the role clinical trials have in treatment of NSCLC. This treatment algorithm has been specifically tailored and developed to assist clinicians in the management of advanced NSCLC.

Keywords: Clinical trials; Maintenance therapy; Molecular aberrations; Non-small cell lung cancer; Overall survival; Progression-free survival.

Figure 1

Treatment algorithm. Stage 4 nonsquamous non-small cell lung cancer (NSCLC) should have their tumors analyzed for epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK), Kirsten rat sarcoma viral oncogene homolog (KRAS) and ROS1 in a Clinical Laboratory Improvement Amendments-certified laboratory setting. For patients with EGFR mutation, we recommend first-line therapy is erlotinib or afatinib or a clinical trial. For patients with ALK or ROS1 rearrangements, we recommend first-line crizotinib therapy. We recommend continuation of targeted therapy until disease progression. Upon disease progression, provided the patient is eligible to receive additional therapy, we next recommend a clinical trial or platinum-doublet systemic chemotherapy for 4-6 cycles with or without bevacizumab (drug holiday). Upon disease progression, provided the patient is eligible to receive additional therapy, we next recommend a clinical trial or another National Comprehensive Cancer Network (NCCN) guideline recommended cytotoxic therapy. For patients with squamous, KRAS mutation, or wild-type for these 4 molecular phenotypes, we recommend platinum-doublet systemic chemotherapy for 4-6 cycles with or without bevacizumab or a clinical trial. Note: bevacizumab should not be administered to patients with squamous cell carcinoma. Those patients with stable disease or better can proceed on maintenance therapy or have a drug holiday. Those with disease progression on first-line therapy or developing disease progression during maintenance therapy or drug holiday, can be evaluated for a clinical trial or another NCCN guideline recommended cytotoxic therapy, provided the patient is eligible to receive additional therapy. ¹Not for squamous cell lung cancer. TKI: Tyrosine kinase inhibitor; PD: Progressive disease; CR: Complete response.