First-line therapy for advanced oesophageal cancer is currently limited to fluoropyrimidine plus platinum-based chemotherapy. We aimed to evaluate the antitumour activity of pembrolizumab plus ...chemotherapy versus chemotherapy alone as first-line treatment in advanced oesophageal cancer and Siewert type 1 gastro-oesophageal junction cancer.
We did a randomised, placebo-controlled, double-blind, phase 3 study across 168 medical centres in 26 countries. Patients aged 18 years or older with previously untreated, histologically or cytologically confirmed, locally advanced, unresectable or metastatic oesophageal cancer or Siewert type 1 gastro-oesophageal junction cancer (regardless of PD-L1 status), measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, and Eastern Cooperative Oncology Group performance status of 0–1, were randomly assigned (1:1) to intravenous pembrolizumab 200 mg or placebo, plus 5-fluorouracil and cisplatin (chemotherapy), once every 3 weeks for up to 35 cycles. Randomisation was stratified by geographical region, histology, and performance status. Patients, investigators, and site staff were masked to group assignment and PD-L1 biomarker status. Primary endpoints were overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 combined positive score (CPS) of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients. This trial is registered with ClinicalTrials.gov, NCT03189719, and is closed to recruitment.
Between July 25, 2017, and June 3, 2019, 1020 patients were screened and 749 were enrolled and randomly assigned to pembrolizumab plus chemotherapy (n=373 50%) or placebo plus chemotherapy (n=376 50%). At the first interim analysis (median follow-up of 22·6 months), pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more (median 13·9 months vs 8·8 months; hazard ratio 0·57 95% CI 0·43–0·75; p<0·0001), oesophageal squamous cell carcinoma (12·6 months vs 9·8 months; 0·72 0·60–0·88; p=0·0006), PD-L1 CPS of 10 or more (13·5 months vs 9·4 months; 0·62 0·49–0·78; p<0·0001), and in all randomised patients (12·4 months vs 9·8 months; 0·73 0·62–0·86; p<0·0001). Pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for progression-free survival in patients with oesophageal squamous cell carcinoma (6·3 months vs 5·8 months; 0·65 0·54–0·78; p<0·0001), PD-L1 CPS of 10 or more (7·5 months vs 5·5 months; 0·51 0·41–0·65; p<0·0001), and in all randomised patients (6·3 months vs 5·8 months; 0·65 0·55–0·76; p<0·0001). Treatment-related adverse events of grade 3 or higher occurred in 266 (72%) patients in the pembrolizumab plus chemotherapy group versus 250 (68%) in the placebo plus chemotherapy group.
Compared with placebo plus chemotherapy, pembrolizumab plus chemotherapy improved overall survival in patients with previously untreated, advanced oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients regardless of histology, and had a manageable safety profile in the total as-treated population.
Merck Sharp & Dohme.
Background
The COVID‐19 outbreak has resulted in collision between patients infected with SARS‐CoV‐2 and those with cancer on different fronts. Patients with cancer have been impacted by deferral, ...modification, and even cessation of therapy. Adaptive measures to minimize hospital exposure, following the precautionary principle, have been proposed for cancer care during COVID‐19 era. We present here a consensus on prioritizing recommendations across the continuum of sarcoma patient care.
Material and Methods
A total of 125 recommendations were proposed in soft‐tissue, bone, and visceral sarcoma care. Recommendations were assigned as higher or lower priority if they cannot or can be postponed at least 2–3 months, respectively. The consensus level for each recommendation was classified as “strongly recommended” (SR) if more than 90% of experts agreed, “recommended” (R) if 75%–90% of experts agreed and “no consensus” (NC) if fewer than 75% agreed. Sarcoma experts from 11 countries within the Sarcoma European‐Latin American Network (SELNET) consortium participated, including countries in the Americas and Europe. The European Society for Medical Oncology‐Magnitude of clinical benefit scale was applied to systemic‐treatment recommendations to support prioritization.
Results
There were 80 SRs, 35 Rs, and 10 NCs among the 125 recommendations issued and completed by 31 multidisciplinary sarcoma experts. The consensus was higher among the 75 higher‐priority recommendations (85%, 12%, and 3% for SR, R, and NC, respectively) than in the 50 lower‐priority recommendations (32%, 52%, and 16% for SR, R, and NC, respectively).
Conclusion
The consensus on 115 of 125 recommendations indicates a high‐level of convergence among experts. The SELNET consensus provides a tool for sarcoma multidisciplinary treatment committees during the COVID‐19 outbreak.
Implications for Practice
The Sarcoma European‐Latin American Network (SELNET) consensus on sarcoma prioritization care during the COVID‐19 era issued 125 pragmatical recommendations distributed as higher or lower priority to protect critical decisions on sarcoma care during the COVID‐19 pandemic. A multidisciplinary team from 11 countries reached consensus on 115 recommendations. The consensus was lower among lower‐priority recommendations, which shows reticence to postpone actions even in indolent tumors. The European Society for Medical Oncology‐Magnitude of Clinical Benefit scale was applied as support for prioritizing systemic treatment. Consensus on 115 of 125 recommendations indicates a high level of convergence among experts. The SELNET consensus provides a practice tool for guidance in the decisions of sarcoma multidisciplinary treatment committees during the COVID‐19 outbreak.
The COVID‐19 pandemic has caused deferral, modification, or cessation of treatment for patients with cancer. This article presents a consensus on prioritizing recommendations across the continuum of sarcoma patient care.
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