Pembrolizumab Plus Chemotherapy vs. Chemotherapy Alone for Advanced Oesophageal Cancer

Fluoropyrimidine with platinum-based chemotherapy is the only option for treating advanced oesophageal cancer. The researcher’s study’s objective was to compare the efficacy of first-line chemotherapy with that of first-line chemotherapy + pembrolizumab in treating advanced oesophageal cancer and Siewert type 1 gastro-oesophageal junction cancer. Researchers conducted a randomized, double-blind, placebo-controlled, stage 3 research at 168 medical facilities in 26 nations. Pembrolizumab 200 mg or placebo was administered intravenously to patients aged 18 and up with 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. Regional, histological, and clinical factors all influenced how participants were randomly distributed. No one knew who was in which group, including patients, researchers, or site employees. Overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma and a PD-L1 combined positive score (CPS) of 10 or more, and all randomized patients, were the primary endpoints of this study. ClinicalTrials.gov identifies this study (NCT03189719) as complete and no longer accepting participants.

Pembrolizumab plus chemotherapy (n=373 [50%]) or placebo plus chemotherapy (n=376 [50%]) was randomly assigned to 749 out of 1,020 patients between July 25, 2017, and June 3, 2019. At the first interim analysis (median follow-up of 22.6 months), patients with 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 randomized 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 randomized 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.

In untreated patients with advanced oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more, pembrolizumab plus chemotherapy showed improved overall survival compared to placebo plus chemotherapy. Additionally, both overall survival and progression-free survival were improved in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomized patients regardless of histology. The treatment had an acceptable safety profile in the total population studied.

Source:https://pubmed.ncbi.nlm.nih.gov/34454674/

Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03189719

Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Mansoor W, Li SH, Sunpaweravong P, Maqueda MA, Goekkurt E, Hara H, Antunes L, Fountzilas C, Tsuji A, Oliden VC, Liu Q, Shah S, Bhagia P, Kato K; KEYNOTE-590 Investigators. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomized, placebo-controlled, phase 3 study. Lancet. 2021 Aug 28;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4. Erratum in: Lancet. 2021 Nov 20;398(10314):1874. PMID: 34454674