A Phase 2 Study of Tislelizumab in Combination With Platinum-Based Chemotherapy as First-line Treatment for Advanced Lung Cancer in Chinese Patients.

OBJECTIVES: This phase 2 study explored tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy as first-line treatment of advanced lung cancer. MATERIAL AND METHODS: Eligible patients had histologically/cytologically confirmed advanced/metastatic nonsquamous non-small cell lung cancer (NSQ), squamous NSCLC (SQ), or extensive-stage small cell lung cancer (SCLC). All patients received tislelizumab 200 mg in combination with 4-6 cycles of platinum-doublet. The NSQ cohort received pemetrexed + platinum Q3W for 4 cycles followed by pemetrexed maintenance, the SQ cohort received paclitaxel + platinum (A) or gemcitabine + platinum (B) Q3W, and the SCLC cohort received etoposide + platinum Q3W. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Progression-free survival (PFS) and tolerability profile were secondary endpoints; exploratory endpoints included overall survival (OS) and predictive biomarkers. RESULTS: Fifty-four patients (NSQ, n = 16; SQ = 21 [SQ-A, n = 15; SQ-B, n = 6]; SCLC, n = 17) were enrolled; as of February 25, 2019, 14 remained on treatment. Confirmed ORRs were 44% (NSQ), 80% (SQ-A), 67% (SQ-B), and 77% (SCLC). Median PFS were 9.0 months (NSQ), 7.0 months (SQ-A), and 6.9 months (SCLC); PFS in SQ-B are not mature. Median OS was not reached in all cohorts except for SCLC (15.6 months). Common treatment-emergent AEs included anemia (79.6%, n = 43) and decreased white blood cell count (74.1%, n = 40). Gene expression analyses revealed distinct patterns by histology type; lower tumor inflammation signature levels were observed among nonresponding patients with NSQ and SCLC. CONCLUSIONS: Tislelizumab plus chemotherapy demonstrated encouraging antitumor activity, was generally well tolerated, and distinct immune- and cell cycle-related gene signatures were associated with efficacy across cohorts.

Comparison of cisplatin- and carboplatin-based third-generation chemotherapy in 1,014 Chinese patients with advanced non-small-cell lung cancer.

The outcome of patients with stage IIIB/IV non-small-cell lung cancer treated with platinum-based chemotherapy as first-line therapy was investigated to determine if cisplatin- or carboplatin-based combination therapy have similar efficacy by comparing the overall survival and safety profile for each combination regimen. A total of 1,014 patients, treated for stage IIIB and IV NSCLC between January 2002 and December 2008, with initial ECOG performance status of 0 and 1, adequate hematologic, hepatic, and renal function, who received at least two cycles of third-generation platinum-based chemotherapy, survived greater than 90 days, and experienced death were included for survival and safety analysis. Of them, 788 patients received cisplatin-based chemotherapy and 226 carboplatin-based. Cisplatin-based regimen yield significant better overall survival with a median survival time of 324 days compared to that of the carboplatin-based regimen of 286 days, attributable to the survival benefit of patients with stage III B (379 days vs. 283 days, Log-rank P=0.003), or with histology of squamous (308 days vs. 262 days, Log-rank P=0.01). Patients of the carboplatin-based arm were more likely to experience thrombocytopenia (OR=0.560, 95% CI=0.332-0.944, P=0.028), while cisplatin-based chemotherapy was associated with more nausea and vomiting (OR=3.720, 95% CI=1.971-7.021, P<0.0001). Non-small-cell lung cancer patients with stage IIIB disease and good performance status have a better survival advantage when treated with third-generation cisplatin-based chemotherapy compared to carboplatin-based regimen, and patients with squamous histology type may have experienced greater survival benefit than those with adenocarcinoma.

Validity study of the EDI-2 in Israeli population.

This study was designed to validate the EDI-2 (1) in an Israeli population. The sample consisted of 29 anorectic patients and 18 recovering anorectics, recruited from six hospitals, and 67 female control subjects matched by age. Results of the validity study indicate that the translated EDI-2 was reliable and valid. Anorectic patients scored higher than the recovering anorectics on most scales. Recovering anorectics resembled the control subjects on most scales except Perfectionism.

Does culture make a difference? Racial/ethnic patterns of completed suicide in San Francisco, CA 1987-1996 and clinical applications.

Completed suicides in San Francisco were examined in the racial groups of African Americans, Asians, Caucasians, Hispanics, and Native Americans for a 10-year period (1987-1996). Comparisons of rates across race and gender showed that both Caucasian men and women had the highest rates. Significant differences were found when racial groups were compared across age groups, gender, and method, but no significant difference was found in the use of firearms as a method of suicide. Differences and similarities are illustrated by comparing Caucasian and Asian patterns of suicide in the areas of (1) suicide in Asian homelands, (2) cultural context, and (3) cultural beliefs regarding psychopathology. A framework relating cultural variables to predisposing client variables is suggested for clinicians and researchers.

Suicide in San Francisco, CA: a comparison of Caucasian and Asian groups, 1987-1994.

Completed suicides in the city of San Francisco, California, were examined across all ages in the racial groups of Caucasians (n = 798) and Asians (n = 124) from 1987 to 1994. A comparison of Caucasians and Asians showed that there were differences between them in their rates across all age groups. The major findings are: (1) Caucasians predominantly used gunshot to complete suicide whereas Asians predominantly used hanging to complete suicide, (2) Asian women over the age of 85 have the highest rates across both groups and genders, (3) Asians, as compared to Caucasians, used fewer drugs and alcohol at time of death. Theoretical connections between differences in suicide and definition of the self, as influenced by culture, are discussed.

Circulating angiotensin-converting enzyme, von Willebrand factor antigen and thrombomodulin in exertional heat stroke.

1. Military recruits frequently succumb to exertional heat stroke during intensive training. Since widespread endothelial injury is often associated with exertional heat stroke, the relationship between changes in three circulating endothelial cell markers (angiotensin-converting enzyme, von Willebrand factor antigen and thrombomodulin) and exertional heat stroke was studied. 2. Twelve recruits who had succumbed to exertional heat stroke during basic physical training (5000 m running) were included in the study. Another 10 age-matched healthy subjects who had gone through the same physical training regimen were selected as controls. 3. Blood was withdrawn on admission and on discharge for analyses of angiotensin-converting enzyme, von Willebrand factor antigen and thrombomodulin. Other physiological parameters and biochemical analyses reflecting renal and liver functions were also recorded. 4. Our results indicated that these subjects with exertional heat stroke exhibited impaired liver function as revealed by the significant elevation of both serum glutamic oxaloacetic transaminase (P < 0.05) and serum glutamic pyruvic transaminase (P < 0.05) as compared with normal healthy control subjects. Unfortunately, these values remained mostly somewhat elevated on discharge, although serum glutamic oxaloacetic transaminase was reduced dramatically. Indices of kidney functions, including creatinine clearance and uric acid and phosphorus secretion, were not significantly different from those observed in healthy controls. 5. Circulating angiotensin-converting enzyme activities in exertional heat stroke patients on admission were significantly lower than in normal subjects (10.68 +/- 2.15 versus 21.21 +/- 3.18 nmol hippuric acid min-1 ml-1, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)