KEY TAKEAWAYS
- The phase 3 KEYNOTE-859 study evaluated pembrolizumab combined with chemotherapy vs. placebo with chemotherapy in HER2-negative G/GEJ adenocarcinoma pts.
- The post hoc analysis showed that adding pembrolizumab to initial chemotherapy retained its benefit in the PFS2 evaluation, similar to PFS.
The KEYNOTE-859 phase 3 trial demonstrated that pembrolizumab combined with chemotherapy notably enhanced the main outcome of OS (average 12.9 vs 11.5 months; HR 0.78; P < 0.0001) and secondary measures such as PFS (6.9 vs 5.6 months; HR 0.76; P < 0.0001) and ORR (51.3% vs 42%; P = 0.00009) in HER2-negative G/GEJ adenocarcinoma patients (pts), compared to solo chemotherapy. The safety of the combined treatment was as anticipated. A further post hoc analysis evaluated the time to tumor progression during follow-up treatment (PFS2).
In the study, 1,579 pts were equally divided to receive either pembrolizumab 200 mg or a placebo intravenously every three weeks, up to 35 cycles, in conjunction with a chosen chemotherapy. The HR and 95% CI for PFS2 were determined using a Cox model stratified by various factors. Data were up to October 3, 2022.
With a median tracking of 31.0 months, roughly 45% pts from both groups underwent additional cancer treatments. Specific therapy usage was consistent across groups. The median PFS2 was 11.2 months in the pembrolizumab group and 10.0 months in the placebo group (HR 0.76, 95% CI 0.68-0.85).
The post hoc analysis indicated sustained benefits of pembrolizumab with first-line chemotherapy when assessing PFS2. This supported its combination with chemotherapy as a new primary treatment for HER2-negative G/GEJ adenocarcinoma.
Source: https://www.annalsofoncology.org/article/S0923-7534(23)00160-6/fulltext
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03675737
Wyrwicz, L., Oh, D., Weber, P., Bai, Y., Ryu, M., Lee, J., Rivera, F., Alves, G.V., Garrido, M., Shiu, K., Fernandez, M.G., Li, J., Lowery, M., Çil, T., Cruz, F., Qin, S., Yin, L., Bordia, S., Bhagia, P., Rha, S. O-3 Additional data from the KEYNOTE-859 study of pembrolizumab plus chemotherapy versus placebo plus chemotherapy for advanced HER2-negative gastric or gastroesophageal junction (G/GEJ) cancer. https://doi.org/10.1016/j.annonc.2023.04.018
