Arndt Vogel, MD

Arndt Vogel, MD, of Hannover Medical School in Germany, who served as discussant of the two studies of immunotherapy in hepatocellular carcinoma, said the findings point to a promising future in the treatment of this malignancy. He commented that the responses observed with nivolumab in CheckMate 459 and with atezolizumab/bevacizumab in GO30140 were quite durable—with some ongoing at 12 months. The hope is that these will translate into longer overall survival.

He found the data for the combination particularly impressive, he said, as improvements were achieved not only in the quantity of responses, but also in the quality. “A complete response rate of 12% and a 24% partial response rate in advanced [hepatocellular carcinoma] is remarkable.”

But treatment with single-agent nivolumab resulted in a median overall survival of 16.4 months. “That is the longest we have ever seen in advanced [hepatocellular carcinoma] in a first-line phase III study. Importantly, there was no early detrimental effect and the benefit of immunotherapy appears to increase over time,” Dr. Vogel continued.

Impact of Subsequent Therapies

Interestingly, even the control arm receiving sorafenib yielded better-than-expected survival, which is in line with the increasing survival times being observed over time: 10.7 months in SHARP, 12.3 months in REFLECT, and 14.7 months in CheckMate 459. This “almost 50%” increase in survival in the control arms is at least partly a result of better subsequent therapies. This makes it harder to reveal survival benefits in the experimental arms, he said.

Nevertheless, like many other trials of the past decade, “CheckMate 459 is negative,” Dr. Vogel acknowledged. This speaks to the need to identify populations who will most benefit from immunotherapies. But at this time, “there is no clinical black and white discriminator of efficacy,” he pointed out.

Altogether, these results add to the body of data suggesting that immunotherapy is active in hepatocellular carcinoma and may offer advantages in terms of tolerability and quality of life, he concluded. Whether monotherapy will be sufficient, or combinations will be better, is still an unanswered question, he said, though he further noted, “Atezolizumab/bevacizumab reached its primary endpoint, showing a clear, significant benefit vs monotherapy and a higher disease control rate.”

Cautious Conclusions

Also commenting on CheckMate 459, ESMO spokesperson Angela Lamarca, MD, PhD, from The Christie NHS Foundation Trust, Manchester, United Kingdom, said that since the study failed to meet its primary endpoint, conclusions regarding nivolumab’s benefits must be made cautiously. In view of this limitation, “these results are unlikely to change the current standard of care,” she said.

Angela Lamarca, MD, PhD

“However, it is becoming more apparent that immunotherapy could have a role for the first-line treatment of advanced [hepatocellular carcinoma] and the differences in response rates are clinically meaningful,” she continued. “The favorable safety profile with nivolumab is also of relevance” and could be important to clinicians and patients, though its higher cost should not be ignored, Dr. Lamarca added. ■

DISCLOSURE: Dr. Vogel has had consulting or advisory roles and served on speakers bureaus for Roche, Bayer, Sanofi, Bristol-Myers Squibb, Lilly, Novartis, Eisai, AstraZeneca, Merck, Incyte, Medac, Ipsen, Servier, Pierre Fabre, MSD, BTG, and Janssen. Dr. Lamarca has received honoraria or consulting fees from Eisai, Nutricia, and Ipsen; has been a member of speakers bureaus for Pfizer, Ipsen, Merck, Incyte, and QED; and has received travel or educational funding from Ipsen, Pfizer, Bayer, Advanced Accelerator Applications, Sirtex, Novartis, Mylan, and Delcath.