Sintilimab With Chemoradiotherapy Improved Event-Free Survival for Patients With High-Risk Nasopharyngeal Carcinoma

In an interview with Oncology Learning Network, Jun Ma, MD, Sun Yat-sen University Cancer Center, Guangzhou, China, discusses results of the phase 3, randomized controlled CONTINUUM trial. This trial evaluated the addition of sintilimab to induction chemotherapy and concurrent chemoradiotherapy for patients with nasopharyngeal carcinoma. These results were first presented at the 2023 American Society of Clinical Oncology (ASCO) Meeting.

Oncology Learning Network (OLN): What were the aims of the phase 3 CONTINUUM trial?

Briefly, [nasopharyngeal carcinoma] (NPC) is a unique head and neck cancer with an extremely unbalanced geographic distribution. NPC has a high incidence in Southeast Asia, North Africa, and especially South China. About half of all NPC cases worldwide were diagnosed in China. Our cancer center, Sun Yat-sen University, is the biggest treatment center for NPC all around the world. We treat over 6,500 patients every year. In 2019, we published a trial in the New England Journal of Medicine. That trial established the induction chemotherapy plus concurrent chemoradiotherapy as the standard of care in locoregionally advanced NPC.

However, despite such intensified treatment, about 20 to 30 [percent] of the patients still experience disease recurrence. This is the unmet need for this population. Interestingly, NPC used to be called lymphoepithelioma because of its abundant infiltration of lymphocytes. Moreover, NPC is characterized by high PD-L1 expression. Most patients had a PD-L1 expression in the tumor, thus the NPC is considered potentially suitable for anti PD-1 immunotherapy. In fact, in current or metastatic NPC, there are 3 phase 3 trials that have demonstrated the efficiency after adding anti PD-1 therapy to chemotherapy. The CONTINUUM trial is the first to evaluate the safety and the efficiency of 18 PD-1 blockades to the curative chemoradiotherapy in locoregional, advanced NPC.

What were the trial methods?

CONTINUUM is a phase 3 randomized trial conducted in 9 Chinese centers. Patients with Stage III or Stage IVA NPC were eligible, excluding those with a lower risk of recurrence. That is patients with T3/T4 lymph nodes negative and T3 in one disease. They were randomized to receive induction chemotherapy and concurrent chemo radiotherapy, or the same treatment plus the sintilimab. Patients in the sintilimab group received 200 milligram sintilimab every 3 weeks for 12 cycles, including 3 cycles before, 3 cycles concurrent, and 6 cycles after radiotherapy.

The primary end point was event-free survival (EFS) which is the most common primary endpoint in trials in locoregional, advanced NPC. Event includes the locoregional recurrence, distant metastasis or deaths, secondary end points including overall survival, distant metastasis-free survival, locoregional recurrence-free survival, safety, and health related quality of life.

What were the results?

The study results are exciting. The 3-year EFS increased by 10% from 76% in the standard group to 86% in the sintilimab group. The risk of developing events was reduced by 41%. The risk of distant metastasis is reduced by 43% while the risk of the locoregional recurrence is reduced by 48%. In this trial, the incidence of the high grade, that is the grade 3 to 4, adverse events is higher in the sintilimab, which is 74% and 64%, respectively.

Adverse events leading to the deaths occurred in 2 patients in the sintilimab group and 1 patient in the standard group. However, the incidence of the high-grade immune-related adverse events was then 10%. These immune-related adverse events usually resolve soon with the dose interruption and [  ] supportive care. Overall, 70% of the patients were able to complete the protocol-defined sintilimab treatment.

What are the significance of these results?

Based on the significant improved EFS and higher but manageable adverse events, the CONTINUUM trial supports the use of sintilimab and maybe other PD-1 inhibitors, plus induction chemotherapy and concurrent chemoradiotherapy in patients with high-risk or locoregional advanced NPC. CONTINUUM is practice-changing, and this agent will become the standard care of locoregional NPC. 

Source:

Ma J, Sun Y, Liu X, et al. PD-1 blockade with sintilimab plus induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) versus IC-CCRT in locoregionally-advanced nasopharyngeal carcinoma (LANPC): A multicenter, phase 3, randomized controlled trial (CONTINUUM). Presented at 2023 ASCO Annual Meeting; June 2-6, 2023; Chicago, Illinois. Abstract #LBA6002