KEY TAKEAWAYS
- Phase 3 trial (KEYNOTE-240) evaluated the efficacy and safety of pembrolizumab (pembro) vs. placebo (pbo) in patients with aHCC previously treated with sorafenib.
- The dual primary endpoints were OS and PFS, assessed by blinded independent central review (BICR) per RECIST v1.1.
- Pembrolizumab demonstrated a statistically significant and clinically meaningful improvement in OS.
- Pembrolizumab also showed a higher ORR of 18.3% vs. 4.4%, longer DOR (median 13.9 vs. 15.2 months), and a higher DCR of 63.3% vs. 55.6% compared to placebo.
- These findings from KEYNOTE-240 and data from other trials (KEYNOTE-224 and KEYNOTE-394) support the long-term efficacy and favorable benefit-risk profile of pembrolizumab in the treatment of aHCC.
Sorafenib-treated patients (pts) with aHCC showed an encouraging ORR with Pembro in KEYNOTE-224, prompting the FDA to fast-track the drug’s approval in the United States. Prespecified statistical significance criteria for OS and PFS were narrowly missed in KEYNOTE-240, despite similar ORR and clinically meaningful improvements in OS and PFS. Patients from Asia treated for aHCC with sorafenib or oxaliplatin-based chemotherapy showed significant and clinically meaningful improvement in OS, PFS, and ORR with pembro compared to pbo in the KEYNOTE-394 trial. After 4.5 years of follow-up, KEYNOTE-240 data are presented. Sorafenib-treated patients with aHCC were randomly assigned to receive either pembro 200 mg IV Q3W or a placebo. According to RECIST v1.1, the primary endpoints were overall survival (OS) and progression-free survival (PFS), both of which were evaluated by blinded, independent central review (BICR). BICR evaluated ORR, DOR, DCR, and TTP as secondary endpoints using RECIST v1.1. Safety was also a primary concern.
The median (range) time from randomization to data cutoff for pembro was 53.9 (46.1-63.1) months, and for pbo, it was 54.1 (46.0-62.2) months as of 8/22/2021. Survival rates for pembro were 13.9 (11.6-16.0) months, and for pbo, they were 10.6 (8.3-13.5) months (HR, 0.774; 95% CI, 0.623-0.963). There was an estimated 17.9% and 11.1% OS rate at 36 and 48 months for pembro and pbo, respectively. PFS for pembro was 3.0 (95% CI: 2.8-4.1) months, while PFS for pbo was 2.8 (1.6-3.0) months (HR: 0.726; 95% CI: 0.577-0.913). At 36 and 48 months, the estimated PFS rates for pembro and pbo were 8.6% and 0%, respectively. Pembro had an ORR (95% CI) of 18.3% (14.0-23.4), while pbo’s was 4.4% (1.6-9.4). Both pembro and pbo had median (range) DORs of 13.9 (1.5+ to 51.0+) months, and 15.2 (2.8-21.9) months, respectively. DCR for pembro was 63.3%, and DCR for pbo was 55.6%. TTP (95% CI) for pembro was 3.8 (2.8-4.4) months, and for pbo, it was 2.8 (1.6-3.0) months. There were no unanticipated or novel side effects.
Pembro, in patients with sorafenib-treated aHCC, improved overall survival (OS) and progression-free survival (PFS) compared to pbo, with a tolerable safety profile. These results and those from the KEYNOTE-224 and KEYNOTE-394 studies further support pembro’s long-term efficacy and favorable benefit-risk profile in treating aHCC.
Source: https://oncologypro.esmo.org/meeting-resources/esmo-congress/pembrolizumab-pembro-vs-placebo-pbo-as-second-line-treatment-for-sorafenib-treated-advanced-hepatocellular-carcinoma-ahcc-4.5-year-follow-up
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02702401
Pembrolizumab (Pembro) vs. placebo (Pbo) as second-line treatment for sorafenib-treated advanced hepatocellular carcinoma (aHCC): 4.5-year follow-up… | OncologyPRO. (n.d.). Oncologypro.esmo.org. Annals of Oncology (2022) 33 (suppl_7): S323-S330. 10.1016/annonc/annonc1057
