Merck and Bristol Myers Squibb Report Significant Reduction in Mortality Risk with PD-1 Inhibitors Keytruda and Opdivo in First-Line Treatment of Gastric and Esophageal Cancers at ESMO 2020

Gastric cancer is the fifth most common cancer worldwide and the third leading cause of cancer-related deaths. In China, gastric cancer is the second most prevalent cancer after lung cancer, accounting for 44% and 50% of the global incidence and mortality rates, respectively. Eighty percent of Chinese patients with gastric cancer are already at an advanced stage at diagnosis, leaving them with limited treatment options and suboptimal therapeutic outcomes. Esophageal cancer is the seventh most common cancer globally and the fourth leading cause of cancer-related deaths in China, following lung, gastric, and liver cancers. The high incidence of esophageal cancer in China may be associated with the dietary habit of consuming food and beverages while they are still very hot.

Today, at the ESMO 2020 Virtual Congress, MSD and Bristol-Myers Squibb (BMS) respectively announced the latest clinical trial results of their respective combination therapies based on their blockbuster PD-1 inhibitors Keytruda and Opdivo for first-line treatment of patients with gastric cancer and esophageal cancer. Let’s take a look at how they performed.

First-line Treatment for Esophageal Cancer: Keytruda-Chemotherapy Combination Reduces Risk of Death by 27%

MSD Announces Results from the Pivotal Phase 3 KEYNOTE-590 Clinical Trial. In this randomized, double-blind clinical trial, patients with locally advanced or metastatic esophageal cancer received combination therapy consisting of Keytruda and platinum-based chemotherapy, or combination therapy consisting of placebo and platinum-based chemotherapy.

At a median follow-up of 10.8 months, the first interim analysis showed that Keytruda combination therapy reduced the risk of death by 27% compared with chemotherapy (HR=0.73, 95% CI, 0.62-0.86, p<0.0001). The median overall survival (OS) was 12.4 months in the Keytruda group versus 9.8 months in the chemotherapy group. Notably, these data were not stratified by patients’ PD-L1 expression levels.

In patients with tumors expressing PD-L1 (CPS > 10), Keytruda combination therapy demonstrated superior efficacy, with a median overall survival (OS) of 13.5 months compared to 9.4 months in the chemotherapy control group. Keytruda combination therapy reduced the risk of death by 38% (HR = 0.62; 95% CI, 0.49–0.78; p < 0.0001).

▲Survival data from the KEYNOTE-590 clinical trial of Keytruda combination therapy (Image source: MSD official website)

Keytruda combination therapy also significantly improved patients’ progression-free survival, reducing the risk of disease progression or death by 35% in the overall population and by 49% in patients with PD-L1–expressing tumors.

Notably, in the Asian patient subgroup, this combination therapy demonstrated superior efficacy compared with the overall patient population, reducing the risk of death by 36% (HR=0.64) and the risk of disease progression or death by 41% (HR=0.59).

▲Subgroup analysis of patients receiving Keytruda combination therapy; the red box highlights data for the Asian patient subgroup (Image source: MSD official website)

MSD plans to submit an application to regulatory authorities based on these positive data.

Opdivo Combination Therapy Reduces Risk of Death by 20% in First-Line Treatment of Patients with Gastric Cancer, Gastroesophageal Junction Cancer, or Esophageal Adenocarcinoma

In the randomized, open-label, phase 3 CheckMate-649 clinical trial, patients with non-HER2-positive advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma received combination therapy consisting of the PD-1 inhibitor Opdivo and chemotherapy, combination therapy consisting of Opdivo and Yervoy, or chemotherapy alone.

Across all patients, the combination therapy of Opdivo and chemotherapy reduced the risk of death by 20% (HR=0.80, 95% CI, 0.68-0.94, p=0.0002). The median OS for patients in the Opdivo combination therapy group was 13.8 months, compared to 11.6 months in the chemotherapy control group.

In patients with tumor PD-L1 expression (CPS > 5), Opdivo combination therapy demonstrated superior efficacy, with a median overall survival (OS) of 14.4 months compared to 11.1 months in the chemotherapy control group. Opdivo combination therapy reduced the risk of death by 29% (HR = 0.71; 98.4% CI, 0.59–0.86; p < 0.0001).

▲Survival data from CheckMate-649 (Image source: BMS official website)

Disease-Free Survival Doubles! Positive Clinical Results of Opdivo Adjuvant Therapy in Postoperative Esophageal Cancer/GEJ Patients

BMS also reported the results of the Phase 3 CheckMate-577 clinical trial evaluating Opdivo as adjuvant therapy in patients with esophageal cancer and gastroesophageal junction (GEJ) cancer.

The trial results demonstrated that the disease-free survival (DFS) for postoperative patients treated with Opdivo reached 22.4 months, significantly superior to the 11.0 months observed in the placebo group (HR=0.69, 96.4% CI, 0.56-0.86, p=0.0003). The median treatment duration was 10 months for patients receiving Opdivo and 9 months for those receiving placebo.

▲Clinical trial data from CheckMate-577 (Image source: BMS official website)

“70–75% of patients with esophageal cancer and gastroesophageal junction (GEJ) cancer fail to achieve a complete response after chemoradiotherapy and surgery, and there are currently no approved adjuvant therapy options to help improve their prognosis,” said Dr. Ronan J. Kelly, Director of the Charles A. Sammons Cancer Center at Baylor University Medical Center. “In CheckMate 577, Opdivo as adjuvant therapy doubled disease-free survival time, positioning it as the potential first adjuvant therapy for this patient population.”

References:

[1] Merck’s KEYTRUDA® (pembrolizumab) Plus Chemotherapy Reduced Risk of Death by 27% Versus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Esophageal Cancer. Retrieved September 21, 2020, from https://www.merck.com/news/mercks-keytruda-pembrolizumab-plus-chemotherapy-reduced-risk-of-death-by-27-versus-chemotherapy-as-first-line-treatment-for-locally-advanced-or-metastatic-esophageal-cancer/

[2] Opdivo (nivolumab) Plus Chemotherapy Demonstrated Significant Overall and Progression-Free Survival Benefits Versus Chemotherapy in First-Line Treatment of Gastric and Esophageal Cancers. Retrieved September 21, 2020, from https://news.bms.com/news/corporate-financial/2020/Opdivo-nivolumab-Plus-Chemotherapy-Demonstrated-Significant-Overall-and-Progression-Free-Survival-Benefits-Versus-Chemotherapy-in-First-Line-Treatment-of-Gastric-and-Esophageal-Cancers/default.aspx

[3] Opdivo (nivolumab) Demonstrated Superior Disease-Free Survival in Patients with Resected Esophageal or Gastroesophageal Junction Cancer Compared to Placebo in the Adjuvant Setting. Retrieved September 21, 2020, from https://news.bms.com/news/details/2020/Opdivo-nivolumab-Demonstrated-Superior-Disease-Free-Survival-in-Patients-with-Resected-Esophageal-or-Gastroesophageal-Junction-Cancer-Compared-to-Placebo-in-the-Adjuvant-Setting/default.aspx

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