Sintilimab Plus Standard Chemotherapy Misses OS End Point in Metastatic Pancreatic Cancer

Sintilimab (Tyvyt) plus standard-of-care chemotherapy failed to demonstrate a significant improvement in overall survival (OS) and progression-free survival (PFS) vs standard-of-care chemotherapy alone but did result in an improved objective response rate (ORR) in patients with metastatic or recurrent pancreatic adenocarcinoma (PDAC), according to findings from the phase 3 CISPD3 trial that were presented during the 2022 Gastrointestinal Cancers Symposium.

The standard of care for PDAC is the chemotherapy combination FOLFIRINOX (folinic acid, fluorouracil, irinotecan hydrochloride, and oxaliplatin) or modified-FOLFIRINOX (mFFX [folinic acid, irinotecan, oxaliplatin followed by fluorouracil]). Researchers in this study investigated whether sintilimab, a human immunoglobin G4 monoclonal antibody that binds to PD-1 and has shown efficacy in other cancer types, could improve outcomes for patients with PDAC in the first or second line.

“Pancreatic cancers are resistant to PD-1 [and] to PD-L1 used as monotherapy, so the chemotherapy may expand the efficacy of immunotherapy,” said Tingbo Liang, chairman of The First Affiliated Hospital at Zhejiang University School of Medicine, in his presentation.

The single-center, open-label phase 3 CISPD3 trial randomized patients 1:1 to receive either 200 mg of sintilimab every 3 weeks plus mFFX (irinotecan 85 mg/m², oxaliplatin 68 mg/m² followed by 5-FU 2400 mg/m²) every 2 weeks versus mFFX alone. Of the study population of 110 total patients, only 3 patients on the sintilimab arm and 5 on the mFFX-alone arm had previous chemotherapy.

Patients were treated until disease progression, unacceptable toxicity, or other reasons for discontinuation. The primary end point was OS, while secondary end points included ORR, PFS, and disease control rate (DCR).

Twenty-one patients receiving sintilimab had a partial response (PR) and 1 had a complete response (CR), while 11 had a PR and none had a CR when receiving mFFX alone. In the sintilimab arm, 11 patients were not evaluable compared with 9 in the mFFX arm. The ORR for sintilimab was 50.0% compared with 23.9% with mFFX alone (P = .05). The duration of response was 7.85 months for sintilimab compared with 4.63 months for mFFX, but this was not statistically significant (P > .05). The DCR was 84.0% and 71.7% for sintilimab and mFFX, respectively (P > .05).

However, the median OS was similar between the 2 arms for the intention-to-treat population: 10.9 months for sintilimab and 10.8 months for mFFX alone with a hazard ratio (HR) of 1.09 (95% CI, 0.70-1.690; P > .05). The median PFS was 5.9 months for sintilimab and 5.73 months for mFFX with a HR of 0.93 (95% CI, 0.62-1.41), showing no improvement in survival outcomes based on these data.

In terms of safety, grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 45 patients (84.9%) in the sintilimab arm compared with 40 (74.1%) in the mFFX-alone arm. The most common grade 3 or higher AE was neutropenia, which was reported in 31 patients (58.5%) given sintilimab and 24 patients (44.4%) given mFFX alone. Other AEs included thrombocytopenia, anemia, vomiting, and increased aminotransferase. Immune-related AEs of grade 3 or higher occurred in 3 patients in the sintilimab arm (5.7%) and pulmonary AEs occurred in 3 patients (5.7%) as well.

“From the study we conclude that from addition of the sinitilimab to the mFFX, we improved the ORR significantly for metastatic pancreatic cancer, but no superior OS and PFS were observed. The toxicity was manageable and acceptable until growth. These data suggest that a combination with PD-1 antibody may expand the benefit of the chemotherapy protocol,” said Liang.

Reference

Fu Q, Chen Y, Huang D, Guo C, et al. Randomized phase III study of sintilimab in combination with modified folfrinox versus folfrinox alone in patients with metastatic and recurrent pancreatic cancer in China: The CISPD3 trial. Presented at: 2022 ASCO Gastrointestinal Cancers Symposium. January 20-22, 2022. Abstract 560. https://bit.ly/3GS5QNg