What is the prognosis and overall survival (OS) in a patient with stage 4 esophageal adenocarcinoma with a combined positive score (CPS) greater than 1, and in a patient with a CPS less than 1?

From the Guidelines

The prognosis for stage 4 esophageal adenocarcinoma varies significantly based on the Combined Positive Score (CPS), with patients having a CPS greater than 1 having a better overall survival (OS) compared to those with a CPS less than 1, as supported by the most recent guideline from the Journal of Clinical Oncology 1.

Key Considerations

• Patients with a CPS greater than 1 may benefit from first-line treatment with pembrolizumab plus chemotherapy, which has shown a median OS of approximately 12-14 months, with some patients experiencing extended survival up to 2 years.
• In contrast, patients with a CPS less than 1 typically have a median OS of 8-10 months with standard chemotherapy alone.
• The improved outcomes in CPS ≥1 patients reflect the tumor's immunogenicity and responsiveness to immunotherapy, as PD-L1 expression indicates potential benefit from immune checkpoint inhibitors.

Treatment Approach

• For CPS ≥1 patients, first-line treatment with pembrolizumab (200mg IV every 3 weeks) plus chemotherapy (fluoropyrimidine and platinum-based regimens) is recommended.
• Treatment response should be assessed every 6-9 weeks initially with imaging.
• Regardless of CPS status, supportive care including nutritional support, dysphagia management, and pain control remains essential.
• Performance status, comorbidities, and patient preferences should guide treatment decisions, as more aggressive regimens may not benefit patients with poor functional status despite favorable CPS scores.

Evidence Base

• The guideline from the Journal of Clinical Oncology 1 provides the most recent and highest quality evidence for the treatment of stage 4 esophageal adenocarcinoma, and is therefore the primary basis for these recommendations.
• Other studies, such as those published in the Journal of the National Comprehensive Cancer Network 1 and the European Journal of Nuclear Medicine and Molecular Imaging 1, provide additional context and support for the use of immunotherapy and chemotherapy in the treatment of esophageal cancer.

From the FDA Drug Label

The major efficacy outcome measure was OS. In an exploratory subgroup analysis in patients with PD-L1 CPS<1 (n=344) at the time of the pre-specified interim analysis of OS, the median OS was 12.7 months (95% CI: 11.4,15.0) for the KEYTRUDA arm and 12.2 months (95% CI: 9.5,14. 0) for the placebo arm, with a HR of 0.92 (95% CI: 0.73,1.17). Table 84: Efficacy Results* for KEYNOTE-859 OS Number (%) of patients with event603 (76)666 (84)464 (75)526 (85)188 (67)226 (83) Median in months (95% CI)12.9 (11.9,14.0)11. 5 (10.6,12.1)13.0 (11.6,14.2)11.4 (10.5,12.0)15.7 (13.8,19.3)11.8 (10.3,12.7)

• Prognosis and Overall Survival (OS):
  • For patients with a CPS greater than 1, the median OS was 12.9 months (95% CI: 11.9,14.0) for the KEYTRUDA arm and 11.5 months (95% CI: 10.6,12.1) for the placebo arm.
  • For patients with a CPS greater than 10, the median OS was 15.7 months (95% CI: 13.8,19.3) for the KEYTRUDA arm and 11.8 months (95% CI: 10.3,12.7) for the placebo arm.
  • For patients with a CPS less than 1, the median OS was 12.7 months (95% CI: 11.4,15.0) for the KEYTRUDA arm and 12.2 months (95% CI: 9.5,14.0) for the placebo arm 2

From the Research

Prognosis and Overall Survival in Stage 4 Esophageal Adenocarcinoma

• The prognosis for patients with stage 4 esophageal adenocarcinoma is generally poor, with less than 5% surviving 5 years 3.
• Treatment for stage 4 disease is typically chemotherapy in selected patients, while the role of radiation therapy and surgical resection remains controversial 3.
• A study found that pembrolizumab combined with chemotherapy has been proven effective as first-line therapy in patients with advanced esophageal cancer, with a median overall survival (OS) of 12.4 months in all randomized patients 4.
• In patients with a combined positive score (CPS) of 10 or more, pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for overall survival, with a median OS of 13.9 months 4.

Comparison of CPS Greater Than 1 and Less Than 1

• A study found that patients with a CPS of 10 or more had a better prognosis than those with a lower CPS, with a median OS of 13.5 months compared to 9.4 months 4.
• However, there is limited information available on the specific comparison of CPS greater than 1 and less than 1 in stage 4 esophageal adenocarcinoma.
• Another study found that treatment mode and metastasis patterns were independent risk factors affecting the overall survival time of patients with stage IV esophageal cancer, but did not specifically examine the impact of CPS 5.

Overall Survival Rates

• The median OS in patients with advanced esophageal cancer was not reached in one study, with a 12-month OS rate of 78.8% and an 18-month OS rate of 72.7% 6.
• In another study, the median OS was 12.4 months in all randomized patients, and 13.9 months in patients with a CPS of 10 or more 4.
• A study found that surgery combined with chemoradiotherapy may improve the OS time of patients with stage IV esophageal adenocarcinoma, but the impact of CPS on this outcome is unclear 5.