An updated overall survival analysis of the phase III HIMALAYA study, now at 5 years, has confirmed the robust benefit for the STRIDE regimen of durvalumab plus tremelimumab in unresectable hepatocellular carcinoma.1 At the European Society for Medical Oncology (ESMO) Congress 2024 (Abstract 947MO), investigators reported a doubling of 5-year survival, which was 19.6% with STRIDE vs 9.4% with sorafenib alone—a 24% reduction in the risk of death. This benefit was accentuated in patients achieving disease control, and no additional safety concerns were observed with extended follow-up.
Lorenza Rimassa, MD
“These results set a new benchmark, with one in five patients alive with STRIDE at 5 years,” said Lorenza Rimassa, MD, Associate Professor of Medical Oncology in the Department of Biomedical Sciences, Humanitas University, Pieve Emanuele and Humanitas Cancer Center, and IRCCS Humanitas Research Hospital in Rozzano, Italy.
“Another important finding is that we observed a classical objective response by [Response Evaluation Criteria in Solid Tumors version 1.1] is not necessary to have long-term survival,” Dr. Rimassa added. The improvement in survival across multiple tumor response categories provides novel insights on the clinical benefit of dual immune checkpoint inhibition beyond conventional measures of response, she said.
Now with 5 years of extensive analyses, Dr. Rimassa stated, “the data are mature…. We can be comfortable with it in our clinical practices and in sharing it with our patients.”
About HIMALAYA
The phase III study enrolled 1,171 patients and randomly assigned them to one of three regimens: STRIDE (tremelimumab at 300 mg plus durvalumab at 1,500 mg followed by durvalumab at 1,500 mg every 4 weeks); sorafenib at 400 mg twice daily; or single-agent durvalumab at 1,500 mg every 4 weeks.
A survival benefit was reported in previous analyses, with durability of survival observed at 48 months.2,3 At the ESMO Congress, Dr. Rimassa reported the first 5-year overall survival analysis and evaluated survival according to tumor response after a median follow-up of about 63 months.
KEY POINTS
- The latest analysis of the phase III HIMALAYA trial shows the 5-year survival advantage for the STRIDE regimen of tremelimumab and durvalumab in unresectable hepatocellular carcinoma.
- One in 5 patients treated with STRIDE remained alive at 5 years, vs 1 in 10 treated with sorafenib (19.6% vs 9.4%).
- The safety profile of the regimen remained unchanged from the primary analysis.
In addition to the survival benefit, which essentially doubled overall for patients receiving STRIDE, those patients achieving disease control had more than a doubling in survival time, from 12.7% with sorafenib to 28.7% with STRIDE. In addition, an exploratory analysis of the depth of response (DpR) showed that more patients treated with the STRIDE regimen experienced deep responses leading to longer survival compared with sorafenib:
- DpR > 75% at 60 months: 72.7% vs 33.3%
- DpR > 50% and ≤ 75%: 57.8% vs 32.1%.
“Even small reductions in tumor diameters can be associated with long-term survival, though, of course, patients with deeper responses are more represented among long-term survivors,” she indicated.
Ghassan Abou-Alfa, MD
Dr. Rimassa said that the rate of treatment-related serious adverse events with STRIDE did not change from the primary analysis. HIMALAYA co-investigator Ghassan Abou-Alfa, MD, commented on this observation: “The safety profile doesn’t change at 5 years. It’s incredible that we are able to see people function with limited adverse events…. Patients can keep going on with their lives, coming in for one injection once a month, and that’s it.”
Disclosure: Dr. Rimassa reported financial relationships with AbbVie, Agios, AstraZeneca, Basilea, Bayer, Eisai, Elevar Therapeutics, Exelixis, FibroGen, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Jazz Pharmaceuticals, Lilly, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, and BMS. Dr. Abou-Alfa reported financial relationships with Arcus, AstraZeneca, Autem, Berry Genomics, BioNTech, Boehringer Ingelheim, BMS, Eisai, Elicio, Exelixis, Genentech/Roche, Helsinn, Incyte, Ipsen, Merck, Novartis, Parker Institute, Pertzye, Puma, QED, Servier, Vector, Yiviva, AbbVie, BioNTech, BMS, Merus, and Tempus. For full disclosures of all study authors, visit cslide.ctimeetingtech.com/esmo2024.
REFERENCES
1. Rimassa L, Chan SL, Sangro B, et al: Five-year overall survival (OS) and OS by tumour response measures from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. ESMO Congress 2024. Abstract 947MO. Presented September 16, 2024.
2. Abou-Alfa GK, Lau G, Kudo M, et al: Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid 1:1-12, 2022.
3. Sangro B, Chan SL, Kelley RK, et al: Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. Ann Oncol 35:448-457, 2024.
