Abstract
Simple SummaryThe use of checkpoint inhibitors has changed the treatment landscape for gastroesophageal cancer in the third-line setting. However, success rates in earlier treatment lines are highly variable across trials. Herein, we compare the efficacy and safety of the different anti-PD-1/PD-L1 regimens with or without chemotherapy.Background: The use of checkpoint inhibitors has changed the treatment landscape for gastroesophageal cancer in the third-line setting. However, success rates in earlier treatment lines are highly variable across trials. Herein, we compare the efficacy and safety of the different anti-PD-1/PD-L1 regimens with or without chemotherapy; Methods: We performed a network meta-analysis (NMA) of anti-PD-1/PD-L1 monotherapy or combined with chemotherapy (chemoimmunotherapy) for gastroesophageal cancers without ERBB2 overexpression; Results: The first-line NMA included four trials (N = 3817), showing that chemoimmunotherapy improved OS and PFS without significant safety difference: Nivolumab-chemotherapy, OS (HR: 0.83 [95% CI, 0.75–0.92]), PFS (HR 0.68 [95% CI, 0.57–0.81]), Pembrolizumab-chemotherapy: OS (HR 0.77 [95% CI, 0.67–0.88]), PFS (HR: 0.72 [95% CI, 0.60–0.85]. Pembrolizumab monotherapy was the safest first-line treatment, SAE (OR 0.02 [95% CI, 0.00–0.2]) but showed no survival benefit. The second-line NMA encompassed four trials (N = 2087), showing that anti-PD-1 significantly improved safety but not survival: camrelizumab, SAE (OR 0.37; [95% CI, 0.24–0.56]); nivolumab, SAE (OR 0.13, [95% CI, 0.08–0.2]) pembrolizumab, SAE (OR 0.4; [95% CI, 0.30–0.53]); Conclusions: chemoimmunotherapy improves OS and PFS in previously untreated gastroesophageal cancers. Anti-PD-1 monotherapies improve safety in refractory disease, with no significant survival benefit.
Highlights
Gastric and esophageal cancers are the third and sixth leading causes of cancer mortality worldwide, with an estimated 768,793 and 544,076 deaths in 2020, respectively [1].The diagnosis usually occurs in patients with locally advanced unresectable or metastatic disease, when treatment options are limited and with no curative intent
The second-line NMA encompassed four trials (N = 2087), showing that anti-programmed death-1 (PD-1) significantly improved safety but not survival: camrelizumab, serious adverse events (SAEs); nivolumab, SAE pembrolizumab, SAE; Conclusions: chemoimmunotherapy improves overall survival (OS) and progression-free survival (PFS) in previously untreated gastroesophageal cancers
We found no significant safety difference in SAE from Nivo-Chemo or Pembrolizumab monotherapy (Pembro)-Chemo SAE (OR, 1.31; 0; 95% confidence interval (95% CI), 0.23–7.35), compared with chemotherapy (Figure 1A)
Summary
Gastric and esophageal cancers are the third and sixth leading causes of cancer mortality worldwide, with an estimated 768,793 and 544,076 deaths in 2020, respectively [1].The diagnosis usually occurs in patients with locally advanced unresectable or metastatic disease, when treatment options are limited and with no curative intent. Chemotherapy remains the primary way to improve survival and quality of life in patients with gastroesophageal cancer For those without overexpression of ERBB2 (previously, HER2), the first-line treatment is usually a choice of a platinum-fluoropyrimidine doublet, resulting in median survival of one year [2,3,4,5]. We compare the efficacy and safety of the different anti-PD1/PD-L1 regimens with or without chemotherapy; Methods: We performed a network meta-analysis (NMA) of anti-PD-1/PD-L1 monotherapy or combined with chemotherapy (chemoimmunotherapy) for gastroesophageal cancers without ERBB2 overexpression; Results: The first-line NMA included four trials (N = 3817), showing that chemoimmunotherapy improved OS and PFS without significant safety difference: Nivolumab-chemotherapy, OS (HR: 0.83 [95% CI, 0.75–0.92]), PFS (HR 0.68 [95% CI, 0.57–0.81]), Pembrolizumab-chemotherapy: OS (HR 0.77 [95% CI, 0.67–0.88]), PFS Anti-PD-1 monotherapies improve safety in refractory disease, with no significant survival benefit
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