Endocrine immune-related adverse event is a prognostic biomarker independent of lead-time bias.

OBJECTIVES: Immune-related adverse events (irAEs) are known to be associated with clinical efficacy and better prognoses in patients receiving immune checkpoint inhibitors. In particular, endocrine irAE (e-irAE) is related to better prognoses. Since the incidence of irAEs increase as treatment duration becomes longer, we should consider lead-time bias not to overvalue the result. We evaluated the impact of e-irAE on the outcome before and after 6-, 9-, and 12-week landmark analyses. MATERIALS AND METHODS: We evaluated 222 patients with advanced or recurrent non-small cell lung cancer who received anti-PD-1 antibodies such as nivolumab or pembrolizumab from January 2016 to April 2021. Treatment efficacy and outcomes of patients with or without e-irAE (e-irAE group or no e-irAE group) were retrospectively evaluated. In addition, we performed 6-, 9-, and 12-week landmark analyses to exclude the effect of lead-time bias. RESULTS: Median progression free survival (PFS) was significantly longer in the e-irAE group than in the no e-irAE group (overall: 15.3 vs 3.9 months, p < 0.0001; 6-week: 15.3 vs 4.9 months, p < 0.0002; 9-week: 19.8 vs 6.1 months, p = 0.0012, 12-week: 19.8 vs 8.4 months, p = 0.017). Overall survival (OS) was significantly longer in the e-irAE group (overall: not reached (NR) vs 15.4 months, p = 0.0003; 6-week: NR vs 19.1 months, p = 0.0049, 9-week: NR vs 22.2 months, p = 0.006; 12-week: NR vs 23.3 months, p = 0.04). We used the multivariate cox proportional hazard model to adjust for confounding factors and found that e-irAE had better impact on both PFS and OS (PFS: overall: hazard ratio 0.37 [95% confidence interval 0.23-0.56], 6-week: 0.41 [0.26-0.63], 9-week: 0.43 [0.24-0.63], 12-week: 0.52 [0.31-0.84]; OS: overall: 0.40 [0.22-0.68], 6-week: 0.46 [0.25-0.79], 9-week: 0.47 [0.24-0.84], 12-week: 0.58 [0.29-1.08]). CONCLUSION: The occurrence of endocrine irAE was associated with better efficacy and prognoses regardless of the lead-time bias.

A randomized phase II trial of gemcitabine plus carboplatin: biweekly versus standard schedules in patients with advanced non-small cell lung cancer.

OBJECTIVE: Gemcitabine combined with carboplatin (GC) is a widely used regimen for advanced non-small cell lung cancer (NSCLC), but clinical outcome is still hampered by its toxicity. We conducted a randomized phase II study of GC and compared biweekly versus standard schedules in patients with advanced NSCLC with respect to toxicity and outcome. METHODS: Forty patients with stage IIIB or IV NSCLC were randomized to receive either a biweekly regimen of GC [gemcitabine (1,000 mg/m(2) on days 1 and 14) and carboplatin (area under the concentration-time curve, AUC = 3 on days 1 and 14)] every 28 days or a standard regimen of GC [gemcitabine (1,000 mg/m(2) on days 1 and 8) and carboplatin (AUC = 5 on day 1)] every 21 days. These cycles were repeated until disease progression. RESULTS: Response rates were 55% for the biweekly regimen and 40% for the standard regimen. Median overall and progression-free survival times were 19.7 and 6.2 months, respectively, for the biweekly regimen, and 11.8 and 2.8 months, respectively, for the standard GC regimen. Hematologic toxicity was prominent. However, the incidence of grade 1 or 2 thrombocytopenia was significantly lower in the biweekly than in the standard GC regimen (p < 0.05). Nonhematologic toxicity was mild. CONCLUSION: A biweekly GC regimen was better tolerated than a standard GC regimen in patients with advanced NSCLC.

Percutaneous coronary intervention without use of guiding catheters for extreme downsizing: the Emperor's new clothes technique.

A 72-year-old male with effort angina pectoris and old myocardial infarction underwent percutaneous coronary intervention (PCI). A 4 Fr sheath was inserted in the radial artery. After diagnostic angiography, a guidewire was inserted from the diagnostic catheter. The diagnostic catheter is removed, and the distal tip of the guidewire remains in the coronary artery. Intravascular ultrasound (IVUS) could be performed via the 4 Fr sheath without guiding catheters. IVUS-guide PCI was successfully performed with 4 Fr sheath, although IVUS requires at least a 5 Fr or larger system. This technique is called "The Emperor's New Clothes Technique" because PCI is performed as if an invisible guiding catheter was being used.