Phase I Trial of Targeted EGFR or ALK Therapy with Ipilimumab in Metastatic NSCLC with Long-Term Follow-Up.

BACKGROUND: The natural histories of, and treatment options for, epidermal growth factor receptor (EGFR)-mutated and anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancers (NSCLCs) are distinctly different from those of lung cancer that lacks actionable mutations. Ipilimumab is a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor that has been approved in other malignancies. OBJECTIVE: A phase I trial of ipilimumab plus targeted therapy with either erlotinib or crizotinib was performed to assess the safety of the combination in patients with EGFR-mutated or ALK-rearranged advanced NSCLC. METHODS: Patients with EGFR-mutated or ALK-rearranged NSCLC on a stable dose of erlotinib or crizotinib for > 28 days were eligible for the study. Patients were treated with ipilimumab 3 mg/kg for four cycles plus erlotinib or crizotinib. RESULTS: Treatment of the EGFR cohort resulted in dose-limiting toxicity in three of eight patients, with grade 3 diarrhea. The protocol was amended to reduce the ipilimumab dose to 1 mg/kg. Excessive toxicity resulted in the study being closed after 14 patients. Four of 11 EGFR-mutated patients ultimately developed grade 3 colitis. Of three ALK-rearranged patients, one developed hypophysitis and another grade 2 pneumonitis. For 11 EGFR-mutated patients, progression-free survival (PFS) from the start of ipilimumab was 17.9 months. Erlotinib treatment began a median 7.7 months before ipilimumab; therefore, erlotinib PFS was 27.8 months. Median overall survival (OS) has not been reached but will be > 42.3 months from erlotinib initiation. For three ALK-rearranged patients, ipilimumab PFS was 24.1 months. Median OS has not been reached but will be at least 47.2 months from the initiation of crizotinib. CONCLUSION: Erlotinib plus ipilimumab caused excessive short-term gastrointestinal toxicity leading to early study closure. However, PFS and OS were notable; therefore, targeted therapies with immunotherapy in NSCLC merit further study. Clinicaltrials.gov registration number: NCT01998126.

Smoking Cessation, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

Cigarette smoking has been implicated in causing many cancers and cancer deaths. There is mounting evidence indicating that smoking negatively impacts cancer treatment efficacy and overall survival. The NCCN Guidelines for Smoking Cessation have been created to emphasize the importance of smoking cessation and establish an evidence-based standard of care in all patients with cancer. These guidelines provide recommendations to address smoking in patients and outlines behavioral and pharmacologic interventions for smoking cessation throughout the continuum of oncology care.