木瓜直播

SAN FRANCISCO -- In patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma, a checkpoint inhibitor combination showed promise in the preoperative setting, while a bispecific antibody added to upfront chemotherapy elicited responses in two-thirds of patients with advanced disease, according to a pair of early-phase trials.

In the first -- the study -- investigators found that neoadjuvant therapy with nivolumab (Opdivo) and ipilimumab (Yervoy) appeared to be effective in patients with resectable microsatellite instability-high/mismatch repair deficient (MSI/dMMR) gastric/GEJ cancers.

The combination, followed by surgery, led to a pathologic complete response in 59% of patients with MSI/dMMR gastric or GEJ adenocarcinoma, reported Thierry Andre, MD, of Sorbonne University in Paris.

In a , a combination of the next-generation PD-1/CTLA-4 bispecific antibody AK104 and chemotherapy demonstrated an objective response rate of 65.9% as a first-line therapy for patients with advanced gastric or GEJ cancer, according to Jiafu Ji, MD, PhD, Peking University Cancer Hospital in Beijing.

The two studies were presented during a fast abstract session at the Gastrointestinal Cancers Symposium.

GERCOR NEONIPIGA

In explaining the rationale behind the study, Andre noted that patients with locally advanced MSI/dMMR gastric and GEJ adenocarcinomas have a better prognosis compared with MMR-proficient cases.

"Perioperative chemotherapy with fluoropyrimidines combined with platinum salt offers questionable benefit in this population and might decrease both event-free and overall survival," he added, and pointed out that dMMR status is predictive for the efficacy of immune checkpoint inhibitors and that using them in this population before and/or after radical surgery might improve outcomes.

The study enrolled 32 patients (median age 65.5 years). Most patients (n=22) had initial stage usT3Nx disease, while four had usT2Nx and six had disease that was not evaluable on ultrasound.

Patients were treated with nivolumab 240 mg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks, followed by radical surgery 5 weeks after the last injection of nivolumab. Patients with Becker tumor regression grade (TRG) <3 were treated with adjuvant nivolumab 480 mg every 4 weeks.

Of the 32 patients, 29 underwent surgery, two had complete endoscopic response with tumor-free biopsies and refused surgery, and one had a metastatic progression and did not undergo surgery.

Of the 29 patients who underwent surgery, 17 had a pathological complete response (TRG 1a as per Becker grade), four had TRG 1b (<10% residual tumor per tumor bed), two had TRG 2 (10-50% of residual tumor), and six had TRG 3 (˃50% of residual tumor).

With a median follow-up of 12 months, 30 patients were alive and without relapse.

As for safety, 25% of patients had grade 3/4 treatment-related adverse events (TRAEs), while 17 patients had perioperative and/or postoperative complications (up until 90 days after surgery).

The study "raises the question whether surgery can be delayed or avoided for some patients with localized MSI/dMMR gastric or [GEJ] adenocarcinoma if immune checkpoint inhibitors are effective," Andre said.

AK104

In their phase Ib/II study, Ji and his colleagues included 96 patients (median age 62.7 years, 70.8% male, 62.5% with ECOG PS 1, and 44.8% with liver metastasis) with unresectable advanced gastric or GEJ adenocarcinoma (regardless of PD-L1 status) and with a history of no prior therapy. Patients with known HER2-positive status were excluded.

Enrolled patients received AK104 (4 mg/kg, 6 mg/kg, 10 mg/kg, once every 2 weeks, or 10 mg/kg, 15 mg/kg once every 3 weeks), plus chemotherapy (either modified XELOX once every 2 weeks, or XELOX once every 3 weeks).

At a median follow-up of 9.95 months, 88 of the 96 patients had at least one post-baseline tumor evaluation. Of those 88 patients, 56 had a partial response, while two had a complete response. Stable disease was reported in another 23 patients, accounting for a disease control rate of 92.0%.

The median duration of response was 6.93 months, with a median time to response of 1.46 months.

Median progression-free survival was 7.1 months (95% CI 5.5-10.48), while median overall survival was 17.41 months (bottom limit of 95% CI 12.35).

TRAEs occurred in 97.9% of patients, the most frequent of which were decreased platelet count (60.4%), decreased white blood cell count (58.3%), reduced neutrophil count (56.3%), anemia (47.9%), nausea (30.2%), vomiting (30.2%), and increased aspartate aminotransferase (30.2%). Grade ≥3 TRAEs occurred in 62.5% of patients.

"AK104 plus chemo presents a potential new first-line treatment option for these patients," observed Ji, who added that a phase III study of AK104 combined with chemotherapy as a first-line therapy for gastric or GEJ cancer is ongoing.

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