KEYNOTE-590 extended follow-up shows pembro + chemo maintains survival in advanced oesophageal cancer

First-line treatment with pembrolizumab + chemotherapy maintains overall survival (OS) and progression-free survival (PFS) in patients with advanced or metastatic oesophageal cancer, according to an additional 12-month follow-up of the KEYNOTE-590* study presented at ASCO GI 2022.

This phase III, double-blind trial involved 749 patients with untreated, advanced/unresectable or metastatic oesophageal cancer or Siewert type 1 gastroesophageal junction (GEJ) adenocarcinoma. Participants were randomized 1:1 to receive either intravenous pembrolizumab 200 mg Q3W for ≤35 cycles plus chemotherapy** (pembro + chemo group; n=373, mean age 64 years) or placebo + chemotherapy (chemo-only group; n=376, mean age 62 years). Patients continued treatment until disease progression, unacceptable toxicity, or study withdrawal and were assessed at an additional follow-up of 12 months. [ASCO GI 2022, abstract 241]

At this extended follow-up (median follow-up 34.8 months), overall, patients in the pembro + chemo group demonstrated longer OS and PFS than those in the chemo-only group (median 12.4 vs 9.8 months; hazard ratio [HR], 0.73 [OS] and median 6.3 vs 5.8 months; HR, 0.64 [PFS]).

The 24-month OS and PFS rates were higher among those treated with pembro + chemo compared with chemo only (26.0 percent vs 16.0 percent [OS] and 12.0 percent vs 3.0 percent [PFS]).

In prespecified subgroup analyses of patients with oesophageal squamous cell carcinoma (ESCC) PD-L1 CPS*** ≥10 tumours, ESCC, or PD-L1 CPS ≥10, median OS was also longer in those treated with pembro + chemo compared with chemo only (13.9 vs 8.8 months; HR, 0.59 [ESCC PD-L1 CPS ≥10], 12.6 vs 9.8 months; HR, 0.73 [ESCC]), and 13.6 vs 9.4 months; HR, 0.64 [PD-L1 CPS ≥10]).

Similarly, the PFS benefit with pembro + chemo vs chemo only was demonstrated in patients with ESCC (6.3 vs 5.8 months; HR, 0.65) and PD-L1 CPS ≥10 (7.5 vs 5.5 months; HR, 0.51).

The longer OS and PFS with pembro + chemo vs chemo only was also observed among patients with adenocarcinoma (median 11.6 vs 9.9 months; HR, 0.73 [OS] and median 6.3 vs 5.7 months; HR, 0.61 [PFS]).

“Generally, OS was improved with pembro + chemo vs chemo across [all] prespecified subgroups,” said lead author Dr Jean-Philippe Metges from CHU Brest-Institut de Cancerologie et d’Hematologie ARPEGO Network in Brest, France.

With regard to antitumour response, patients on pembro + chemo demonstrated a higher overall response rate than those on chemo only (45.0 percent vs 29.3 percent), with more patients responding for ≥24 months (20.4 percent vs 6.2 percent).

There was no change in EORTC QLQ-30 global health status/quality of life (QoL) score (least squares mean [LSM] difference from baseline, -0.10) and EORTC QLQ-OES 18 pain and dysphagia scores (LSM difference from baseline, -2.94 and -5.54, respectively) between the pembro + chemo and chemo-only groups.

Grade ≥3 treatment-related adverse events occurred in 98.4 percent of patients in the pembro + chemo group and 97.3 percent in the chemo-only group. It is important to note that with this longer follow-up, no new or additional side effects were observed, Metges noted.

“With an additional 12 months of follow-up, first-line pembro + chemo continued to provide clinically meaningful benefit, … with a manageable safety profile and stable QoL … in all patients with locally advanced and metastatic oesophageal cancer including GEJ adenocarcinoma,” said Metges.

“These longer-term data further support first-line pembrolizumab + chemo as a new standard of care [in this population],” he added.

*KEYNOTE-590: First-line esophageal carcinoma study with chemo vs. chemo plus pembrolizumab

**Chemotherapy: Intravenous 5-fluorouracil 800 mg/m² on days 1–5 Q3W for ≤35 cycles + cisplatin 80 mg/m² Q3W for ≤6 cycles

***CPS: Combined positive score