NCT01494558.

The aim of this paper is to explore the efficacy of whole brain radiotherapy (WBRT) versus WBRT concurrent with erlotinib in patients with multiple brain metastases of lung adenocarcinoma. WBRT was administered at 30Gy/10f in both arms. In the combination arm, 150 mg erlotinib was given each day, starting the first day of radiotherapy and continuing for 1 month following the end of radiotherapy. Thereafter, pemetrexed or docetaxel monotherapy or the best supportive therapy was given to both arms. The intracranial objective response rate and the local progression-free survival (LPFS) were primary endpoints. Toxicity, progression-free survival (PFS) and overall survival (OS) were secondary endpoints. Thirty-one patients in the WBRT group and 23 patients in the combination group were enrolled from November 2009 to December 2011. In the WBRT and the combination arms, respectively, the objective response rate was 54.84% and 95.65% (P = 0.001), the median local progression-free survival was 6.8 months and 10.6 months (P = 0.003), the median PFS was 5.2 months and 6.8 months (P = 0.009), and median OS was 8.9 months and 10.7 months (P = 0.020). In the combination group, there were no differences of LPFS, PFS, and OS between the epidermal growth factor receptor (EGFR) mutation patients and EGFR wild-type patients. No Grade 4 or higher side effects were observed in either group. A multivariate analysis indicated that erlotinib was the most important prognostic factor for a prolonged survival. Data showed that erlotinib in combination with WBRT had a tolerable toxicity profile and prolonged the LPFS, PFS, and OS of lung adenocarcinoma patients with multiple brain metastases compared with WBRT monotherapy.

Background: Recent research has supported that a variety of cytokines play important roles during radiation-induced lung toxicity. The present study is designed to investigate the differences in early cytokine induction after radiation in sensitive (C57BL/6) and resistant mice (C3H).

Lessons Learned Radiotherapy plus anti–PD‐1 antibody as first‐line therapy is safe and feasible in locally advanced esophageal squamous cell carcinoma (ESCC). Tumor‐infiltrating and peripheral lymphocytes were associated with patient survival. Further studies combining chemoradiotherapy with immunotherapy in locally advanced ESCC and exploration of predictive biomarkers are warranted. Background We conducted a phase Ib study of radiotherapy plus programmed cell death protein 1 (PD‐1) monoclonal antibody camrelizumab as first‐line treatment for locally advanced esophageal squamous cell carcinoma (ESCC). Methods We planned to enroll 20 patients with newly diagnosed locally advanced ESCC. Patients received 60 Gy radiation (2.0 Gy/fraction, 5 fractions/week), with camrelizumab (200 mg every 2 weeks) starting with radiotherapy and continuing for 32 weeks (i.e., for 16 cycles). The primary endpoints were safety and feasibility. Secondary endpoints were rates of radiologic and pathologic response, overall survival (OS), and progression‐free survival (PFS). Study data were collected by the week during radiotherapy (RT), every month during the maintenance camrelizumab treatment, and every 3 months after treatment. Tumor microenvironment and peripheral blood were monitored at baseline and after 40 Gy radiation for association with efficacy. Results Twenty patients were enrolled and received treatment. One patient (patient 10) was excluded upon discovery of a second tumor in the bladder during treatment, leaving 19 patients for analysis. Toxicity was deemed tolerable. Fourteen (74%) patients had assessed objective response. At a median follow‐up time of 31.0 months (95% confidence interval [CI], 27.0–35.1), median OS and PFS times were 16.7 months (95% CI, 5.9–27.9) and 11.7 months (95% CI, 0–30.3), respectively. OS and PFS rates at 24 months were 31.6% and 35.5%, respectively. Kaplan‐Meier analysis revealed associations between the following factors and OS/PFS: tumor programmed cell death ligand 1 (PD‐L1) expression, PD‐1+CD8+, PD‐1+CD4+ T cells, and PD‐L1+CD4+ T cells; peripheral blood CD4+, CD8+, CD4+ regulatory T cells, and their subsets. Conclusion Radiotherapy plus camrelizumab had manageable toxicity and antitumor efficacy for locally advanced ESCC. Several biomarkers were associated with clinical benefit and deserve further study.

Patients with locally advanced esophageal squamous cell carcinoma (ESCC) show poor survival after concurrent chemoradiotherapy. This study investigated the safety and feasibility of combining concurrent chemoradiotherapy with the anti-PD-1 antibody camrelizumab as first-line treatment for these patients. In this phase 1b study (ClinicalTrials.gov NCT03671265), patients received concurrent chemotherapy (cisplatin [25 mg/m 2 ] plus docetaxel [25 mg/m 2 ] for 4 weeks) and radiotherapy (2.0 Gy/fraction, total 60 Gy) with camrelizumab (200 mg every 2 weeks for 32 weeks). Primary endpoints were safety and tolerability, and health-related quality of life. Secondary endpoints were radiological and pathological response rates, overall survival (OS), and progression-free survival (PFS). Candidate biomarkers in tumor and peripheral blood were monitored at baseline and after 40 Gy radiation. Twenty patients were enrolled. The most common treatment-related grade 3 adverse events included radiation esophagitis (20%) and esophageal fistula (10%). Serious treatment-related adverse events occurred in eight (40%) patients. No treatment-related deaths were reported. Health-related quality of life did not deteriorate. Thirteen (65%) patients had an objective response after 40 Gy radiation. At a median follow-up of 23.7 months (95% CI 21.9–24.5), OS and PFS time ranged from 8.2–28.5 and 4.0–28.5 months, respectively. The 12-month and 24-month OS rate was 85.0% and 69.6%; PFS rate was 80.0% and 65.0%. Tumor PD-L1 expression and CD11c + dendritic cells and peripheral-blood IL-27, IL-15, Eotaxin-3, and IL-22 were associated with OS. First-line concurrent chemoradiotherapy plus camrelizumab had a manageable safety profile and promising antitumour efficacy for ESCC, and deserves further study.