Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer.

BACKGROUND: In an interim analysis of this phase 3 trial, the addition of pembrolizumab to chemotherapy resulted in longer progression-free survival than chemotherapy alone among patients with advanced triple-negative breast cancer whose tumors expressed programmed death ligand 1 (PD-L1) with a combined positive score (CPS; the number of PD-L1-staining tumor cells, lymphocytes, and macrophages, divided by the total number of viable tumor cells, multiplied by 100) of 10 or more. The results of the final analysis of overall survival have not been reported. METHODS: We randomly assigned patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer in a 2:1 ratio to receive pembrolizumab (200 mg) every 3 weeks plus the investigator's choice of chemotherapy (nanoparticle albumin-bound paclitaxel, paclitaxel, or gemcitabine-carboplatin) or placebo plus chemotherapy. The primary end points were progression-free survival (reported previously) and overall survival among patients whose tumors expressed PD-L1 with a CPS of 10 or more (the CPS-10 subgroup), among patients whose tumors expressed PD-L1 with a CPS of 1 or more (the CPS-1 subgroup), and in the intention-to-treat population. Safety was also assessed. RESULTS: A total of 847 patients underwent randomization: 566 were assigned to the pembrolizumab-chemotherapy group, and 281 to the placebo-chemotherapy group. The median follow-up was 44.1 months. In the CPS-10 subgroup, the median overall survival was 23.0 months in the pembrolizumab-chemotherapy group and 16.1 months in the placebo-chemotherapy group (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.55 to 0.95; two-sided P = 0.0185 [criterion for significance met]); in the CPS-1 subgroup, the median overall survival was 17.6 and 16.0 months in the two groups, respectively (hazard ratio, 0.86; 95% CI, 0.72 to 1.04; two-sided P = 0.1125 [not significant]); and in the intention-to-treat population, the median overall survival was 17.2 and 15.5 months, respectively (hazard ratio, 0.89; 95% CI, 0.76 to 1.05 [significance not tested]). Adverse events of grade 3, 4, or 5 that were related to the trial regimen occurred in 68.1% of the patients in the pembrolizumab-chemotherapy group and in 66.9% in the placebo-chemotherapy group, including death in 0.4% of the patients in the pembrolizumab-chemotherapy group and in no patients in the placebo-chemotherapy group. CONCLUSIONS: Among patients with advanced triple-negative breast cancer whose tumors expressed PD-L1 with a CPS of 10 or more, the addition of pembrolizumab to chemotherapy resulted in significantly longer overall survival than chemotherapy alone. (Funded by Merck Sharp and Dohme; KEYNOTE-355 ClinicalTrials.gov number, NCT02819518.).

Effects of depression and anxiety on mortality in a mixed cancer group: a longitudinal approach using standardised diagnostic interviews.

BACKGROUND: Distress and psychiatric morbidity in cancer patients are associated with poorer outcomes including mortality. In this study, we examined the prevalence of psychiatric morbidity and its association with cancer survival over time. METHODS: Participants were 467 consecutive adult cancer patients attending oncology follow-ups at a single academic medical centre. Assessment consisted of the Hospital Anxiety and Depression Scale and Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision. Comparison between co-morbid psychiatric cases and non-cases was made in follow-ups of up to 24 months. RESULTS: Of the 467 patients, 217 of 220 patients with elevated total Hospital Anxiety and Depression Scale scores (≥16) met the criteria for an Axis I disorder at 6 months follow-up, with 102 of the follow-up sample having a persistent diagnosable psychiatric disorder after 1 year. The most frequent initial diagnoses were minor depression (17.6%), major depressive disorder (15.8%) and adjustment disorder (15.8%). Cancer patients without psychiatric morbidity had a survival benefit of 2.24 months or 67 days. Mean survival at 24 months was 20.87 months (95% CI 20.06-21.69) for cancer patients with psychiatric morbidity versus 23.11 months (95% CI 22.78-23.43) for those without (p < 0.001 for log rank). After adjusting for demographics and cancer stage on a Cox proportional hazards model, psychiatric morbidity remained associated with worse survival (hazard ratio 4.13, 95% CI 1.32-12.92, p = 0.015). CONCLUSIONS: This study contributes to the growing body of evidence linking psychiatric morbidity to cancer mortality. Treating underlying psychiatric conditions in cancer may therefore improve not just quality of life but also survival.