ABSTRACT
BACKGROUND: Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase I/II data show activity of nivolumab in previously treated SCLC. PATIENTS AND METHODS: CheckMate 331 is a randomized, open-label, phase III trial of nivolumab versus standard chemotherapy in relapsed SCLC. Patients with relapse after first-line, platinum-based chemotherapy were randomized 1 : 1 to nivolumab 240 mg every 2 weeks or chemotherapy (topotecan or amrubicin) until progression or unacceptable toxicity. Primary endpoint was overall survival (OS). RESULTS: Overall, 284 patients were randomized to nivolumab and 285 to chemotherapy. Minimum follow-up was 15.8 months. No significant improvement in OS was seen with nivolumab versus chemotherapy [median OS, 7.5 versus 8.4 months; hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.72-1.04; P = 0.11]. A survival benefit with nivolumab was suggested in patients with baseline lactate dehydrogenase ≤ upper limit of normal and in those without baseline liver metastases. OS (nivolumab versus chemotherapy) was similar in patients with programmed death-ligand 1 combined positive score ≥1% versus <1%. Median progression-free survival was 1.4 versus 3.8 months (HR, 1.41; 95% CI, 1.18-1.69). Objective response rate was 13.7% versus 16.5% (odds ratio, 0.80; 95% CI, 0.50-1.27); median duration of response was 8.3 versus 4.5 months. Rates of grade 3 or 4 treatment-related adverse events were 13.8% versus 73.2%. CONCLUSION: Nivolumab did not improve survival versus chemotherapy in relapsed SCLC. No new safety signals were seen. In exploratory analyses, select baseline characteristics were associated with improved OS for nivolumab.
Subject(s)
Lung Neoplasms , Small Cell Lung Carcinoma , Antineoplastic Combined Chemotherapy Protocols , Humans , Lung Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Nivolumab/adverse effects , Progression-Free Survival , Small Cell Lung Carcinoma/drug therapyABSTRACT
BACKGROUND: Malignant pleural mesothelioma (MPM) frequently express elevated AKT/mTOR activity. Previous reports in gliomas, colon, breast and prostate cancer suggest that PTEN/PI3K pathway may be important for the induction of PD-L1 expression. This study explored the expression of PTEN/PI3K pathway and PD-L1 in MPM and its relationship with the patientÌs prognosis MATERIAL AND METHODS: Twenty seven consecutive MPM patients were reviewed. Formalin-fixed, paraffin-embedded tissue biopsies were used for immunohistochemical analysis of PTEN/PI3K pathway and PD-L1 RESULTS: Expression of PTEN, mTOR, pAKT, p4EBP1, peif4E, pS6 and FOXO3a was found in 88.5%, 92.3%, 78.3%, 38.5%, 100%, 52.2% and 100% of tumors and PD-L1 in 23%. We found a significant correlation between pAKT, FOXO3a and PD-L1 expression and longer overall survival (p <0.05). We did not identify significant association between the level of PD-L1 expression and alterations in PI3K pathway CONCLUSIONS: This study shows PTEN/PI3K pathway and PD-L1 in MPM are frequently activated. Our results suggests that there is not association between PD-L1 and the involvement of the PI3K pathway in MPM.
