Frontline Pembrolizumab Combo Obtains EU Approval for HER2+ Gastric Cancer

News
Article

Data from the phase 3 KEYNOTE-811 trial highlight a trend towards improved overall survival among patients with HER2-positive, PD-L1–positive advanced gastric or gastroesophageal junction adenocarcinoma receiving pembrolizumab, trastuzumab, and chemotherapy.

The FDA granted accelerated approval to pembrolizumab, trastuzumab, and chemotherapy as a treatment for locally advanced or metastatic gastric or GEJ carcinoma that is HER2 positive in May 2021.

The FDA granted accelerated approval to pembrolizumab, trastuzumab, and chemotherapy as a treatment for locally advanced or metastatic gastric or GEJ carcinoma that is HER2 positive in May 2021.

The European Commission has approved a combination of pembrolizumab (Keytruda) plus trastuzumab (Herceptin) and fluoropyrimidine- and platinum-based chemotherapy for the frontline treatment of patients with locally advanced unresectable or metastatic HER2-positive, PD-L1–positive gastric or gastroesophageal junction (GEJ) adenocarcinoma, according to a press release from Merck.1

The approval was supported by findings from the phase 3 KEYNOTE-811 study (NCT03615326) in which investigators reported a statistically significant improvement in progression-free survival and objective response rate with the pembrolizumab combo vs trastuzumab and chemotherapy.2 A trend towards improved overall survival was also observed in the experimental arm, although it was not considered to be statistically significant.

“Patients in the [European Union] EU diagnosed with HER2-positive advanced gastric cancer [have] an aggressive disease associated with a poor prognosis, underscoring the need for additional first-line treatment options for these patients,” Scot Ebbinghaus, MD, vice president of global clinical development at Merck Research Laboratories, said in the press release. “With today’s approval of [pembrolizumab], we’re proud that patients whose tumors express PD-L1 with a combined positive score [of 1 or higher] and health care providers in the EU will have an option that includes immunotherapy for this difficult-to-treat disease.”

The FDA granted accelerated approval to pembrolizumab, trastuzumab, and chemotherapy as a treatment for locally advanced or metastatic gastric or GEJ carcinoma that is HER2 positive in May 2021.3 The regulatory decision was also based on data from the phase 3 KEYNOTE-811 study.

References

  1. European Commission approves KEYTRUDA® (pembrolizumab) plus trastuzumab and chemotherapy as first-line treatment for HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma expressing PD-L1 (CPS ≥1). News release. Merck. August 29, 2023. Accessed August 29, 2023. https://bit.ly/3PhgAeA
  2. KEYTRUDA® (pembrolizumab) plus trastuzumab and chemotherapy met primary endpoint of progression-free survival as first-line treatment in patients With HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. News release. Merck. News release. June 16, 2023. Accessed August 29, 2023. bit.ly/3p903iB
  3. FDA approves Merck’s KEYTRUDA (pembrolizumab) combined with trastuzumab and chemotherapy as first-line treatment in locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma. News release. Merck. May 5, 2021. Accessed August 29, 2023. https://bit.ly/2SjmdOj
Recent Videos
Those being treated for peritoneal carcinomatosis may not have to experience the complication rates or prolonged recovery associated with surgical options.
For patients with peritoneal carcinomatosis, integrating PIPAC into a treatment regimen does not interrupt their systemic therapy.
According to Benjamin J. Golas, MD, PIPAC could be used as a bridging therapy before surgical debulking or between subsequent large surgical operations.
According to Benjamin Golas, MD, PIPAC is emerging as minimally invasive laparoscopic approach for patients with peritoneal carcinomatosis.
According to Ronan J. Kelly, deciding whether to give nivolumab- or durvalumab-based regimens in gastric cancers may rely on a patient’s frailty.
Five-year follow-up revealed that patients treated with nivolumab vs placebo in the phase 3 CheckMate 577 trial experienced a “doubling” of survival.
Patients treated with nivolumab in the phase 3 CheckMate 577 trial were less likely to experience progression-related treatment discontinuation vs placebo.
Testing a patient’s genetics may influence decisions such as using longer courses of radiotherapy, says Rachit Kumar, MD.
Related Content
Data from the phase 3 INAVO120 trial support the approval of inavolisib-based treatment for patients with PIK3CA+, ER+/HER2– disease in the EU.

Inavolisib Combo Receives EU Approval in PIK3CA+ ER+/HER2– Breast Cancer

Russ Conroy
July 24th 2025
Article

Data from the phase 3 INAVO120 trial support the approval of inavolisib-based treatment for patients with PIK3CA+, ER+/HER2– disease in the EU.

Benjamin Golas, MD, discusses how the use of PIPAC may work in conjunction with systemic chemotherapy for those with peritoneal carcinomatosis.

Harnessing PIPAC to Improve Outcomes in Peritoneal Carcinomatosis

Benjamin J. Golas, MD
June 30th 2025
Podcast

Benjamin Golas, MD, discusses how the use of PIPAC may work in conjunction with systemic chemotherapy for those with peritoneal carcinomatosis.

Subcutaneous Daratumumab Approved by EC in Smoldering Multiple Myeloma

Subcutaneous Daratumumab Approved by EC in Smoldering Multiple Myeloma

Ariana Pelosci
July 23rd 2025
Article

Results from the AQUILA trial led to the approval of subcutaneous daratumumab for patients with smoldering multiple myeloma at risk of developing the disease.

The approval of sotorasib plus panitumumab is a “welcome step” in KRAS G12C-mutated colorectal cancer, according to Marwan G. Fakih, MD.

Sotorasib Combo Approval May Address Novel Therapy Need in KRAS G12C+ CRC

Marwan G. Fakih, MD
February 24th 2025
Podcast

The approval of sotorasib plus panitumumab is a “welcome step” in KRAS G12C-mutated colorectal cancer, according to Marwan G. Fakih, MD.

EU approval of the agent is based on phase 2b ReNeu trial results, which met its primary end point of confirmed objective response rate in NF1-PN.

Mirdametinib Earns Conditional European Approval in Adult/Pediatric NF1-PN

Roman Fabbricatore
July 21st 2025
Article

EU approval of the agent is based on results from the phase 2b ReNeu trial, which met its primary end point of confirmed objective response rate in NF1-PN.

Radiotherapy Plus Sintilimab and Chemo Improves pCR in Rectal Cancer

Radiotherapy Plus Sintilimab and Chemo Improves pCR in Rectal Cancer

Tim Cortese
July 20th 2025
Article

Short-course radiotherapy combined with sintilimab plus oxaliplatin-capecitabine yielded a pCR rate of 59.2% vs 32.7% with the control arm in locally advanced rectal cancer.