An early-phase clinical trial of nivolumab with radiotherapy in patients with relapsed unresectable/recurrent gastric cancer demonstrated prolonged patient survival.
Gastric cancer is one of the leading causes of cancer-related deaths worldwide. The standard treatment is resection with or without perioperative chemotherapy.1 However, in patients with unresectable or metastatic gastric cancer, chemotherapy is the standard therapy.1 Recently, immune checkpoint inhibitors (ICIs) have proved effective in cancer therapy.1 PD-1 and PD-L1 are inhibitory ICIs that have emerged as a treatment strategy in advanced gastric cancer.1 Blocking PD-L1 expression by PD-1 inhibitors has improved cancer treatment outcomes in some patients, but only a small percentage have any meaningful response.2 The use of ICIs in combination with anticancer agents can potentially improve patient response to therapy.2
Nivolumab is a monoclonal antibody that blocks the interaction among PD-1, PD-L1, and PD-L2.1 The phase 1/2 CIRCUIT clinical trial evaluated the use of nivolumab combined with radiotherapy in patients with unresectable or recurrent advanced gastric cancer who had failed standard chemotherapy.3 The study enrolled 40 patients who received localized radiotherapy (22.5 Gy/5 fractions/5 days) on days 1 to 5 to their largest or symptomatic lesion. This was followed by nivolumab, dosed at 3 mg/kg on days 15 to 22 every 2 weeks for a total of 6 administrations.3 The primary study end point was the disease control rate of the non-irradiated target lesions. Secondary study end points included safety, median survival rate, and the proportion of local control rate for irradiated lesions.
When the abscopal effect was analyzed, 1 patient had achieved a complete response, 5 patients achieved partial responses, 3 patients maintained stable disease, 15 patients had progressive disease, and 16 patients were not able to be evaluated. Local irradiated lesion control evaluation discovered 5 patients with complete response, 6 patients with partial response, 5 patients with stable disease, 4 patients with progressive disease, and 20 patients who were non-evaluable. There was a disease control rate of 22.5% and the response rate was 15%. The median survival was 230 days, and the 1-year survival rate was 28.6%. Evaluation of adverse events (AEs) found 19% of patients had anemia and 12% reported a loss of appetite. There were 16 participants who experienced grade ≥3 AEs.
In this early-phase study, nivolumab with radiotherapy prolonged patient survival time, setting the stage for further investigation.
Source: Kono K, Mimura K, Ogata T, et al. Phase I/II clinical trial of combination of anti-PD-1 mAb, nivolumab with radiotherapy for unresectable and recurrent gastric cancer who failed to standard chemotherapy. Ann Oncol. 2021;32(suppl_5): S1053-S1054.
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