Health-related quality-of-life analysis from KEYNOTE-590: pembrolizumab plus chemotherapy versus chemotherapy for advanced esophageal cancer.

BACKGROUND: In the KEYNOTE-590 study, first-line pembrolizumab plus chemotherapy provided statistically significant improvement in overall survival, progression-free survival, and objective response rate compared with chemotherapy, with a manageable safety profile in patients with advanced esophageal cancer. Prespecified health-related quality-of-life (HRQoL) outcomes are reported. MATERIALS AND METHODS: Change from baseline to week 18 in the EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) global health status/QoL (GHS/QoL) and QLQ-Esophageal cancer module (OES18) dysphagia, pain, and reflux scales were evaluated. RESULTS: The HRQoL analysis included 730 patients who received treatment and completed ≥1 HRQoL assessment. Least squares mean (LSM) change from baseline to week 18 was similar between treatment groups for QLQ-C30 GHS/QoL and physical functioning and QLQ-OES18 reflux scales. The QLQ-OES18 dysphagia (LSM difference, -5.54; 95% CI, -10.93 to -0.16) and pain (LSM difference, -2.94; 95% CI, -5.86 to -0.02) scales favored pembrolizumab plus chemotherapy over placebo plus chemotherapy. Median time to confirmed deterioration (TTD) was similar between treatment groups for QLQ-C30 GHS/QoL and physical functioning and QLQ-OES18 dysphagia and reflux scales. Compared with chemotherapy, pembrolizumab plus chemotherapy prolonged median TTD, as seen on the QLQ-OES18 pain scale (HR, 0.69; 95% CI, 0.51 to 0.95). CONCLUSION: The use of pembrolizumab plus chemotherapy maintained HRQoL at week 18 relative to baseline and was comparable with placebo plus chemotherapy. These HRQoL results together with published reports of efficacy, support the use of pembrolizumab plus chemotherapy as first-line therapy for advanced/metastatic esophageal cancer. CLINICALTRIALS.GOV ID: NCT03189719.

Atezolizumab Plus PEGPH20 Versus Chemotherapy in Advanced Pancreatic Ductal Adenocarcinoma and Gastric Cancer: MORPHEUS Phase Ib/II Umbrella Randomized Study Platform.

BACKGROUND: The MORPHEUS platform comprises multiple open-label, randomized, phase Ib/II trials designed to identify early efficacy and safety signals of treatment combinations across cancers. Atezolizumab (anti-programmed cell death 1 ligand 1 [PD-L1]) was evaluated in combination with PEGylated recombinant human hyaluronidase (PEGPH20). METHODS: In 2 randomized MORPHEUS trials, eligible patients with advanced, previously treated pancreatic ductal adenocarcinoma (PDAC) or gastric cancer (GC) received atezolizumab plus PEGPH20, or control treatment (mFOLFOX6 or gemcitabine plus nab-paclitaxel [MORPHEUS-PDAC]; ramucirumab plus paclitaxel [MORPHEUS-GC]). Primary endpoints were objective response rates (ORR) per RECIST 1.1 and safety. RESULTS: In MORPHEUS-PDAC, ORRs with atezolizumab plus PEGPH20 (n = 66) were 6.1% (95% CI, 1.68%-14.80%) vs. 2.4% (95% CI, 0.06%-12.57%) with chemotherapy (n = 42). In the respective arms, 65.2% and 61.9% had grade 3/4 adverse events (AEs); 4.5% and 2.4% had grade 5 AEs. In MORPHEUS-GC, confirmed ORRs with atezolizumab plus PEGPH20 (n = 13) were 0% (95% CI, 0%-24.7%) vs. 16.7% (95% CI, 2.1%-48.4%) with control (n = 12). Grade 3/4 AEs occurred in 30.8% and 75.0% of patients, respectively; no grade 5 AEs occurred. CONCLUSION: Atezolizumab plus PEGPH20 showed limited clinical activity in patients with PDAC and none in patients with GC. The safety of atezolizumab plus PEGPH20 was consistent with each agent's known safety profile. (ClinicalTrials.gov Identifier: NCT03193190 and NCT03281369).

Immunotherapy in gastrointestinal cancer: Recent results, current studies and future perspectives.

The new therapeutic approach of using immune checkpoint inhibitors as anticancer agents is a landmark innovation. Early studies suggest that immune checkpoint inhibition might also be effective in patients with gastrointestinal cancer. To improve the efficacy of immunotherapy, different strategies are currently under evaluation. This review summarises the discussion during the European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cancer Translational Research Meeting in Mainz in November 2014 and provides an update on the most recent results of immune therapy in gastrointestinal cancers. Knowledge of potential relationships between tumour cells and their microenvironment including the immune system will be essential in gastrointestinal malignancies. In this context, the density of T cell infiltration within colorectal cancer metastases has been associated with response to chemotherapy, and a high expression of programmed cell death ligand 1 (PD-L1) in advanced gastric cancer has been related with poor prognosis. Effective targets might include neo-antigens encoded from genes carrying tumour-specific somatic mutations. Tailored immunotherapy based on such mutations could enable the effective targeting of an individual patient's tumour with vaccines produced on demand. Other strategies considering checkpoint inhibitors have shown efficacy by targeting cytotoxic T-lymphocyte-associated protein 4 and PD-1 or PD-L1. DNA mismatch repair-deficient tumours appear to be potentially the best candidates for these therapies. Finally, the combination of oncolytic viruses with immunotherapy might boost antitumour activity as well. Further evaluation of these promising immunological therapeutic approaches will require large prospective clinical studies.

[Merkel cell cancer of the skin: population-based incidence and survival, 1995-2005]. / Carcinoma de células de Merkel cutáneo: incidencia y supervivencia poblacional, 1995-2005.

BACKGROUND AND OBJECTIVE: We aimed to assess the population-based incidence and survival of primary Merkel cell carcinoma. MATERIAL AND METHOD: From January 1995 to December 2005, 19 patients diagnosed with primary Merkel cell carcinoma were recruited in the population-based Cancer Registry of Girona. RESULTS: The age-adjusted incidence was 1,3 per 10(6) person-year; higher in males (1,5) than in females (1,1). Cases occurred mostly in people older than 65 years (94,7%), especially involving the head (79%). CONCLUSIONS: To our knowledge, this study is the first to define the incidence and survival of Merkel cell carcinoma in Europe. The age-adjusted incidence of primary Merkel cell carcinoma in our area is similar than the age-adjusted incidence of the 2000 US standard population.

Carcinoma de células de Merkel cutáneo: incidencia y supervivencia poblacional, 1995–2005 / Merkel cell cancer of the skin: population-based incidence and survival, 1995–2005

Fundamento y objetivo: Conocer la incidencia y supervivencia poblacional del carcinoma de células de Merkel. Material y método: De enero de 1995 a diciembre de 2005 se registraron un total de 19 casos de carcinoma primario de células de Merkel en la población cubierta por el Registro de Cáncer Poblacional de Girona. Resultados: La incidencia ajustada por edad a la población estándar mundial fue de 1,3 casos por 106 personas-año, siendo superior en varones (1,5) que en mujeres (1,1), con predominio de los casos en mayores de 65 años (94,7%). La región anatómica de la cabeza fue la localización afectada con mayor frecuencia (79%). Conclusiones: Se trata del primer trabajo, en nuestro conocimiento, que estima la incidencia y la supervivencia poblacional del carcinoma de células de Merkel en Europa. La incidencia observada en nuestra área es similar a la incidencia observada en EE. UU (AU)

Background and objective: We aimed to assess the population-based incidence and survival of primary Merkel cell carcinoma. Material and method: From January 1995 to December 2005, 19 patients diagnosed with primary Merkel cell carcinoma were recruited in the population-based Cancer Registry of Girona. Results: The age-adjusted incidence was 1,3 per 106 person-year; higher in males (1,5) than in females (1,1). Cases occurred mostly in people older than 65 years (94,7%), especially involving the head (79%). Conclusions: To our knowledge, this study is the first to define the incidence and survival of Merkel cell carcinoma in Europe. The age-adjusted incidence of primary Merkel cell carcinoma in our area is similar than the age-adjusted incidence of the 2000 US standard population (AU)