Effect of immunotherapy-infusion time of day on survival of patients with advanced cancers: a study-level meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the standard of care for numerous malignancies. Emerging evidence suggests that the time of day (ToD) of ICI administration could impact the outcomes of patients with cancer. The consistency of ToD effects on ICI efficacy awaits initial evaluation. MATERIALS AND METHODS: This meta-analysis integrates progression-free survival (PFS) and overall survival (OS) data from studies with a defined 'cut-off' ToD. Hazard ratios (HRs) [95% confidence interval (CI)] of an earlier progression or death according to 'early' or 'late' ToD of ICIs were collected from each report and pooled. RESULTS: Thirteen studies involved 1663 patients (Eastern Cooperative Oncology Group performance status 0-1, 83%; males/females, 67%/33%) with non-small-cell lung cancer (47%), renal cell carcinoma (24%), melanoma (20%), urothelial cancer (5%), or esophageal carcinoma (4%). Most patients received anti-programmed cell death protein 1 or anti-programmed death-ligand 1 (98%), and a small proportion also received anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) (18%). ToD cut-offs were 13:00 or 14:00 (i.e. ICI median infusion time), for six studies, and 16:00 or 16:30 (i.e. reported threshold for weaker vaccination responses) for seven studies. Pooled analyses revealed that the early ToD groups had longer OS (HR 0.50, 95% CI 0.42-0.58; P < 0.00001) and PFS (HR 0.51, 95% CI 0.42-0.61; P < 0.00001) compared with the late ToD groups. CONCLUSIONS: Patients with selected metastatic cancers seemed to largely benefit from early ToD ICI infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking. Prospective randomized trials are needed to establish recommendations for optimal circadian timing of ICI-based cancer therapies.

[Adjuvant chemotherapy of non-small cell lung cancer: Tolerance of combined cisplatin-pemetrexed therapy]. / Traitement adjuvant des cancers bronchiques non à petite cellules : tolérance de l'association platine-pemetrexed.

RATIONALE: Adjuvant chemotherapy is standard for non-small cell lung cancer (NSCLC) after surgical resection. In this context, the tolerance of the treatment is an essential criterion in the choice of chemotherapy. This exploratory study evaluated, in the situation of adjuvant chemotherapy, the tolerance of combined cisplatin-pemetrexed. The study analyzed a cohort of non-squamous NSCLC patients treated in an adjuvant setting by combined cisplatin (75 mg/m(2)) and pemetrexed (500 mg/m(2)), under vitamin B12 and folic acid cover, 4 cycles at 21-day intervals. RESULTS: The analysis included 23 patients (age: 58.7 ± 5 years, men: 56%, average creatinin clearance (Clea): 94 ± 22 mL/min, average haemoglobin: 13.8 ± 1.6g/dL). Over 92 planned courses, 7.6% are postponed (neutropenia), 4.3% were not given (asthenia). We noted 7 episodes of vomiting (4 grade 3), with two hospitalizations in the same patient; 5 episodes of anaemia grade 1-2 not requiring EPO prescription or transfusion and no febrile neutropenia. At the end of the treatment, three patients had a Clea<50 mL/mn and 5 a haemoglobin between 9 and 11 g/dL. CONCLUSION: Combined cisplatin-pemetrexed in an adjuvant situation has a satisfactory tolerance.