NICE Recommends Pembrolizumab Plus Chemo for Untreated HER2– Superior Gastric/GEJ Adenocarcinoma

The Nationwide Institute for Well being and Care Excellence has really helpful the advertising and marketing authorization of pembrolizumab (Keytruda) paired with platinum- and fluoropyrimidine-based chemotherapy for the remedy of sufferers with untreated domestically superior unresectable for metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors have a PD-L1 mixed constructive rating (CPS) of at the very least 1.¹

The advice is predicated on findings from the section 3 KEYNOTE-859 trial (NCT03675737), during which the addition of the immunotherapy to chemotherapy (n = 790) considerably prolonged total survival (OS) vs chemotherapy alone (n = 789), at 12.9 months (95% CI, 11.9-14.0) vs 11.5 months (95% CI, 10.6-12.1), translating to a 22% discount within the danger of loss of life (HR, 0.78; 95% CI, 0.70-0.87; P < .0001).²

In these with a PD-L1 CPS of 1 or increased, those that obtained pembrolizumab plus chemotherapy (n = 618) skilled a median OS of 13.0 months (95% CI, 11.6-14.2) vs 11.4 months (95% CI, 10.5-12.0) with chemotherapy alone (n = 617; HR, 0.74; 95% CI, 0.65-0.84; P < .0001). In these with a PD-L1 CPS of 10 or increased, the median OS with pembrolizumab (n = 279) was 15.7 months (95% CI, 13.8-19.3) vs 11.8 months (95% CI, 10.3-12.7) with out (n = 272; HR, 0.65; 95% CI, 0.53-0.79; P < .0001).

The addition of pembrolizumab to chemotherapy additionally resulted in a considerably longer progression-free survival (PFS) vs chemotherapy alone, at a median of 6.9 months (95% CI, 6.3-7.2) and 5.6 months (95% CI, 5.5-5.7), respectively (HR, 0.76; 95% CI, 0.67-0.85; P < .0001). In these with a CPS of 1 or increased, the median PFS with pembrolizumab was 6.9 months (95% CI, 6.0-7.2) vs 5.6 months (95% CI, 5.4-5.7) with out (HR, 0.72; 95% CI, 0.63-0.82; P < .0001). In these with a PD-L1 CPS of 10 or increased, the median PFS with pembrolizumab was 8.1 months (95% CI, 6.8-8.5) vs 5.6 months (95% CI, 5.4-6.7) with out (HR, 0.62; 95% CI, 0.51-0.76; P < .0001).

“We’re happy that entry to a further remedy choice will likely be made accessible for some folks dwelling with abdomen most cancers and gastroesophageal junction most cancers,” Katie Midday, interim chief govt officer at Guts UK, said in a information launch.¹ “For eligible sufferers, this information will likely be warmly welcomed as it might give folks extra alternative and options relating to appropriate therapies.”

The double-blind, randomized, section 3 examine enrolled sufferers with histologically or cytologically confirmed adenocarcinoma of the abdomen or GEJ that was domestically superior however unresectable or metastatic.² Sufferers had been at the very least 18 years of age, had tumors that had been HER2 unfavourable, had measurable illness by RECIST 1.1 standards and had not obtained prior remedy. They had been required to have an ECOG efficiency standing of 0 or 1 and had acceptable organ operate.

If sufferers had squamous cell or undifferentiated gastric most cancers, recognized historical past of hepatitis C an infection, immunodeficiency or historical past of receiving persistent systemic immunosuppressive remedy, or a recognized historical past of human immunodeficiency virus, they had been excluded. Sufferers additionally couldn’t have energetic autoimmune illness in want of remedy or energetic central nervous system metastases.

Sufferers had been randomly assigned 1:1 to obtain pembrolizumab at 200 mg or placebo on day 1 of every 3-week cycle for as much as 35 cycles. Chemotherapy regimens had been chosen by investigators and included fluorouracil at 800 mg/m² each day given constantly on days 1 to five of every 3-week cycle plus cisplatin at 80 mg/m² on day 1 of every 3-week cycle or capecitabine at 1000 mg/m² given twice each day on days 1 to 14 of every 3-week cycle plus oxaliplatin at 130 mg/m² on day 1 of every 3-week cycle.

The trial’s major finish level was OS and secondary finish factors included PFS, goal response fee, DOR, and security.

Stratification elements included geographical area (western Europe, Israel, North America, and Australia vs Asia vs remainder of the world), PD-L1 CPS (<1 vs ≥1), and investigator’s alternative of chemotherapy (fluorouracil plus cisplatin vs capecitabine plus oxaliplatin).

Extra information confirmed that within the intention-to-treat (ITT) inhabitants, 51.3% of those that obtained pembrolizumab plus chemotherapy achieved an goal response vs 42.0% of those that obtained chemotherapy alone (P = .0001). On this inhabitants, the median period of response (DOR) was 8.0 months (95% CI, 7.0-9.7) within the pembrolizumab arm vs 5.7 months (95% CI, 5.5-6.9) within the chemotherapy-alone arm. In these with a PD-L1 CPS or 1 or increased, 52% vs 43% of sufferers achieved an goal response; the median DORs had been 8.3 months (95% CI, 7.0-10.9) and 5.6 months (95% CI, 5.4-6.9). In these with a PD-L1 CPS of 10 or increased, 61% and 43% of sufferers, respectively, achieved an goal response; the median DORs had been 10.9 months (95% CI, 8.0-13.8) and 5.8 months (95% CI, 5.3-7.0).

Concerning security, no new security indicators had been noticed. Therapy-related toxicities that had been grade 3 to five occurred in 59% of sufferers within the pembrolizumab arm (n = 785) vs 51% of these within the chemotherapy-alone arm (n = 787). The most typical grade 3 to five antagonistic results of any trigger had been anemia (12% vs 10%) and decreased neutrophil depend (10% vs 8%). Immune-mediated AEs had been reported in 27.0% vs 9.0% of sufferers, respectively. AEs led to loss of life for 1.0% vs 2.0% of sufferers.¹

References

1. NICE recommends MSD’s KEYTRUDA (pembrolizumab) with platinum- and fluoropyrimidine-based chemotherapy for untreated HER2-negative superior gastric or gastro-oesophageal junction adenocarcinoma. Information launch. MSD. July 26, 2024. Accessed July 26, 2024.
2. Rha SY, Oh D-Y, Yañez P, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative superior gastric most cancers (KEYNOTE-859): a multicentre, randomised, double-blind, section 3 trial. Lancet Oncol. 2023;24(11):P1181-P1195. doi:10.1016/S1470-2045(23)00515-6