Novel Triple Therapy Promising Option for Gastric Cancer

M. Alexander Otto, PA, MMS

November 02, 2022

The report covered in this summary was published on as a preprint and has not yet been peer reviewed.

Key Takeaway

  • A novel combination of a PD-1 inhibitor, a VEGFR-2 tyrosine kinase inhibitor, and chemotherapy led to a median overall survival of more than a year in patients with previously treated, inoperable gastric/gastroesophageal junction (GEJ) cancer in a single-arm study.

Why This Matters

  • The prognosis for advanced, refractory gastric/GEJ cancer is poor, and better second- and later-line treatments are needed.

  • Dual therapy — PD-1 inhibition plus either chemotherapy or VEGFR-2 blockade — has shown promise in past studies. 

  • The researchers combined all three options — PD-1 blockade, VEGFR-2 inhibition, and chemotherapy — into one regimen.

  • The results indicated an improvement in outcomes compared with findings reported in previous trials evaluating regimens with one or two agents.

Study Design

  • The trial included 28 evaluable patients with previously treated, inoperable metastatic or recurrent gastric or GEJ adenocarcinoma.

  • Patients had progressed on either first-line fluorouracil plus platinum or second-line paclitaxel/irinotecan.

  • Subjects received the anti–PD-1 sintilimab (approved in China) at 200 mg every 3 weeks; the VEGFR-2 inhibitor apatinib at 250 mg daily; and either irinotecan every 2 weeks or paclitaxel every 3 weeks at provider discretion.

  • Apatinib and sintilimab were continued for up to 2 years and chemotherapy for up to 6 months, or until disease progression or intolerable toxicity.

  • Imaging was performed every 6-8 weeks.

Key Results

  • The objective response rate (ORR) was 53.6% over a median follow-up of 12.3 months. 

  • Median progression-free survival (PFS) was 8.5 months and median overall survival (OS) 12.5 months.

  • These results appear promising compared with previous trials evaluating one-drug or two-drug combinations. For instance, in the RAINBOW study, ramucirumab combined with paclitaxel in a similar patient population led to an ORR of 28%, median PFS of 4.4 months, and median OS of 9.6 months.

  • In the current study, patients with liver metastases had substantially higher ORR, PFS, and OS than those without liver metastases, and patients with intestinal type histology had higher ORR and longer PFS. 

  • Overall tolerance was good, possibly because chemotherapy and apatinib doses were lower than when used as monotherapy, the authors noted.

  • The most frequent grade 3-4 adverse event was neutropenia (13.3%). Others included elevated liver enzymes, elevated alkaline phosphatase, elevated gamma-glutamyl transpeptidase, hyperbilirubinemia, and proteinuria.

  • There were no treatment-related deaths.


It was a small, single-center study with no control group.


  • The work was funded by Beijing Xisike Clinical Oncology Research Foundation.

  • The investigators reported no disclosures.

This is a summary of a preprint research study, “Sintilimab Plus Apatinib and Chemotherapy as Second‑ /Third-Line Treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: A Prospective, Single-Arm, Phase II Trial,” led by Le Zhang of the Tianjin Medical University Cancer Institute and Hospital, China, provided to you by Medscape. The study has not been peer reviewed. The full text can be found at

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who has worked for several major news outlets before joining Medscape and also an MIT Knight Science Journalism fellow. Email:

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