5/26/2023 0 Comments Her2 postie received zalota“Importantly, patients were enrolled based on histology as opposed to tumor location. The primary end points of the trial for nivolumab plus chemotherapy versus chemotherapy were OS and PFS by blinded independent central review in patients whose tumors expressed PD-L1 with a CPS of 5 or greater. Participants were randomized to receive nivolumab at 360 mg every 3 weeks or 240 mg every 2 weeks plus chemotherapy comprised of XELOX every 3 weeks or FOLFOX every 2 weeks, nivolumab plus ipilimumab (Yervoy), or chemotherapy. Those with HER2 positivity were excluded from the trial. Patients with previously treated, unresectable advanced, or metastatic gastric cancer, GEJ cancer, or esophageal adenocarcinoma were enrolled to the trial, irrespective of PD-L1 expression. The phase 3 CheckMate-649 trial (NCT02872116) was a larger study than KEYNOTE-062. There was no benefit for pembrolizumab compared with chemotherapy or pembrolizumab with chemotherapy.”ĬheckMate-649 Introduces New Standard First-Line Treatment Option “Nonetheless, the study was heartbreaking to everyone because it did not change practice. Statistically, it was underpowered and had too many complicated alphas and questions to answer,” said Janjigian. “This was an eagerly awaited study, but relatively poorly designed with a small sample size. 05) or a CPS of 10 or greater, at a median of 6.9 months versus 6.4 months, respectively (HR, 0.84 95% CI, 0.70-1.02 P =.04). Moreover, pembrolizumab plus chemotherapy was not superior to chemotherapy for OS in patients with a CPS of 1 or greater, at a median of 12.5 months versus 11.1 months, respectively (HR, 0.85 95% CI, 0.70-1.03 P =. The PD-1 inhibitor prolonged OS versus chemotherapy in patients with a CRPS of 10 or greater, at a median of 17.4 months versus 10.8 months, respectively (HR, 0.69 95% CI, 0.49-0.97). Single-agent pembrolizumab was not superior to chemotherapy alone in patients with a CPS of 1 or greater. Results showed that pembrolizumab was noninferior to chemotherapy in terms of OS in patients with a CPS of 1 or greater, at a median OS of 10.6 months versus 11.1 months, respectively (HR, 0.91 99.2% CI, 0.69-1.18). The primary end points of the trial were overall survival (OS) and progression-free survival (PFS) in patients with PD-L1 CPS of 1 or greater or 10 or greater. 2Ī total of 763 patients were randomized 1:1:1 to receive pembrolizumab at 200 mg (n = 256) pembrolizumab plus chemotherapy which was comprised of cisplatin at 80 mg/m2 on day 1 plus fluorouracil (5-FU) at 800 mg/m2 on days 1 to 5 or capecitabine 1000 mg/m2 twice daily (n = 257) or chemotherapy plus placebo (n = 250) every 3 weeks. The randomized, controlled, partially blinded phase 3 KEYNOTE-062 trial (NCT02494583) enrolled patients with untreated, locally advanced, unresectable, or metastatic gastric/gastroesophageal junction (GEJ) cancer with a PD-L1 CPS of 1 or greater. However, 2020 was a groundbreaking year.” When their tumors are PD-L1 negative, they feel like you’re withholding some therapy from them, but really doesn’t benefit them. That’s part of the frustration that experience. “Disappointingly, with anti–PD-1 therapy alone, CPS-low expressors benefit very little. “TMB has been approved for pembrolizumab as well, although it’s important to know that for gastric cancer, pretty much all patients who have TMB-high tumors are also MSI high that’s really our niche,” said Janjigian. Additionally, pembrolizumab (Keytruda) was approved by the FDA for use in the third-line setting in patients with a PD-L1 combined positive score (CPS) of 1 or higher, tumor mutational burden (TMB) of 10 or higher, or those with microsatellite instability–high tumors. In Asia, the PD-1 agent nivolumab (Opdivo) was approved for use as third-line treatment in patients with adenocarcinoma, regardless of PD-L1 expression status. Checkpoint inhibitors are typically given after disease progression on standard chemotherapy, usually in the third-line setting, said Janjigian. Immunotherapy is an approach that is utilized in later lines of treatment in gastric cancer. “We’re going to examine what’s to come in 20 for anti–PD-1 combination strategies and review some of the molecular features that will allow us to understand how to time treatments and allow our patients to achieve maximum benefits with maximum options to maximize cures,” said Janjigian, associate attending physician and associate professor of Weill Cornell Medical College, and chief of Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center, in a virtual presentation during the 2020 Ruesch Center Symposium. Janjigian, MD, who added that certain molecular features will affect response and inform treatment selection and timing. Future research efforts are focused on examining anti–PD-1 combination strategies, particularly with HER2-directed therapies, according to Yelena Y.
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