Background: CameL phase 3 study demonstrated the superiority of camrelizumab plus chemotherapy over chemotherapy alone for progression-free survival in patients with previously untreated advanced non-squamous non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations. Here, we present the 5-year outcomes. Methods: Patients were randomized (1:1) and received 4–6 cycles of camrelizumab plus carboplatin and pemetrexed (n=205) or carboplatin and pemetrexed (n=207) every 3 weeks, followed by maintenance camrelizumab plus pemetrexed or pemetrexed only. Crossover from chemotherapy group to camrelizumab monotherapy was permitted after disease progression. Results: Median time from randomization to data cut-off was 65.2 months (range, 59.7–72.2). HR for overall survival (OS) was 0.74 (95% CI 0.58 to 0.93; one-sided p=0.0043), and was 0.62 (95% CI 0.49 to 0.79; one-sided p<0.0001) after adjustment for crossover. Five-year OS rates were 31.2% (95% CI 24.7% to 37.9%) with camrelizumab plus chemotherapy versus 19.3% (95% CI 13.9% to 25.3%) with chemotherapy alone. Among the 33 patients who completed 2 years of camrelizumab, 5-year OS rate was 84.3% (95% CI 66.4% to 93.2%), and 5-year duration of response rate was 46.5% (95% CI 24.9% to 65.6%) in the 32 responders. No new safety signals were noted. Conclusions: Camrelizumab plus carboplatin and pemetrexed as first-line therapy continued to demonstrate long-term OS benefit over carboplatin and pemetrexed, with manageable toxicity. Patients who completed 2 years of camrelizumab had enduring response and impressive OS. Current 5-year updated analysis further supports camrelizumab plus carboplatin and pemetrexed as a standard-of-care for previously untreated advanced non-squamous NSCLC without EGFR/ALK alterations. Trial registration number: NCT03134872.

Use of chimeric antigen receptors (CARs), as an immune cell therapy, has generated excellent clinical outcomes against hematologic tumors in recent years. Among them, the CAR-NK (natural killer) therapy has shown better efficacy, and less toxicity, than chimeric antigen receptor T-cell (CAR-T) therapy. In our phase II clinical trials, administering chimeric costimulatory converting receptor (CCCR)-NK92 cells on advanced non-small cell lung cancer patients proved efficacious in cell and animal experiments. However, we observed occurrence of cytokine release syndrome (CRS), a rare and unexpected side effect, never reported before during CAR-NK therapy. Here, we provide a detailed report of the patient’s case, emphasize on the need to pay attention to CRS in NK cell therapy, and suggest improvements that will minimize potential toxicity.

Background: The benefit of systemic treatments in esophageal squamous cell carcinoma (ESCC) which has progressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established. We aimed to compare the efficacy of irinotecan plus S‐1 with S‐1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum‐ or taxane‐based chemotherapy. Methods: We conducted a prospective randomized, multicenter, open‐label, phase 3 trial in 15 centers across China. Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC, and were randomly assigned (ratio, 1:1) to receive either irinotecan plus S‐1 (intravenous infusion of irinotecan [160 mg/m ² ] on day 1 and oral S‐1 [80–120 mg] on days 1–10, repeated every 14 days) or oral S‐1 monotherapy (80–120 mg/day on days 1–14, repeated every 21 days) using a central computerized minimization procedure. The primary endpoint was progression‐free survival (PFS). Results: Between December 23, 2014 and July 25, 2016, we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S‐1 regimen ( n = 61) or S‐1 monotherapy ( n = 62). After a median follow‐up of 29.2 months (95% confidence interval [CI] 17.5–40.9 months), the median PFS was significantly longer in the irinotecan plus S‐1 group than in the S‐1 monotherapy group (3.8 months [95% CI 2.9–4.3 months] vs. 1.7 months [95% CI 1.4–2.7 months], hazard ratio = 0.58, 95% CI 0.38–0.86, P = 0.006). The objective response rates were 24.6% in the irinotecan plus S‐1 group and 9.7% in the S‐1 monotherapy group ( P = 0.002). The patients in the irinotecan plus S‐1 group presented with increased rates of grade 3–4 leukopenia (16.4% vs. 0%), neutropenia (14.8% vs. 1.6%), and nausea (4.9% vs. 0%). No significant difference in grade 3–4 diarrhea and no treatment‐related deaths were observed in both groups. Conclusions: The combination of irinotecan with S‐1 was similarly tolerable but significantly prolonged PFS compared to S‐1 monotherapy as a second‐ or third‐line treatment in patients with recurrent or metastatic ESCC. Clinical Trial Registration NCT02319187. Registered on December 9, 2014

Radiotherapy plays a major role in the management of brain metastases. This study aimed to identify the subset of patients with multiple brain metastases who may not benefit from whole brain irradiation (WBI) due to a short survival time regardless of treatment. We analyzed a total of 339 patient records with brain metastases treated with whole brain radiotherapy from January 2009 to January 2016. External beam radiotherapy techniques were used to deliver 33 Gy in 11 fractions (4 fractions per week) to the whole brain. Eight clinical factors with a potential influence on survival were investigated using the Kaplan-Meier method. All factors with a P < 0.05 in univariate analysis were entered into multivariate analysis using Cox regression. In the present series of 339 patients, median survival time was 2.5 months (M; range, 0–61 months). Four risk factors Karnofsky Performance Score (KPS) < 70, age > 70, > 3 of metastases intracranial, uncontrolled primary tumor) were identified that were significant and negatively correlated with median survival time. Patients with no risk factors had a median survival of 4.7 M; one risk factor, 2.5 M; two risk factors, 2.3 M; and 3–4 risk factors, 0.4 M (p < 0.00001). Patients with identified risk factors might have a negatively impacted overall survival after WBI. Accordingly, patients who will not benefit from WBI can be easily predicted if they have 3–4 of these risk factors.