Bayer quietly claims its liver cancer prize

Bayer will this week claim an important prize for its multi-kinase inhibitor Stivarga as the new standard of care for second-line treatment of unresectable hepatocellular carcinoma.

The positive outcome of its Resorce trial will have important commercial implications for the group, especially given the approaching patent expiry on Nexavar. It might be savvy to conduct studies to move Stivarga up to the first-line setting, but here Bayer would face competition from Eisai’s Lenvima and Bristol-Myers Squibb’s Opdivo, which are both already in such trials (see tables below).

The German group yesterday disclosed the data it will present at the World Congress on Gastrointestinal Cancer on Thursday from Resorce, its pivotal study of Stivarga. These show that its drug conferred a statistically significant 2.8-month survival advantage in second-line HCC, with a 38% reduction in the risk of death.

Resorce study results
Stivarga Placebo Stats
Median OS* 10.6 months 7.8 months HR=0.62 (p<0.001)
Median PFS 3.1 months 1.5 months HR=0.44 (p<0.001)
Median TTP 3.2 months 1.5 months HR=0.46 (p<0.001)
Disease control rate 65.2% 36.1% p<0.001
Overall response rate 10.6% 4.1% p=0.005
*primary endpoint.

This level of benefit should be sufficient to ensure that Stivarga becomes the new standard for patients failing on or intolerant to first-line HCC treatment, which is Bayer’s own Nexavar.

Bayer disclosed that the 573-patient Resorce study had rendered a positive outcome some two months ago, but it held the full data back for presenting fresh to oncologists this week. However, it managed to do so with such a lack of ballyhoo that few noticed, which was all the more remarkable given that the study had broken a decade-long run of negative results in HCC.

Of course Stivarga has already been launched for other indications – colorectal cancer and gastrointestinal stromal tumours – though sales are modest, reaching $347m last year. Given its commercial availability patients might get the drug ahead of a formal HCC approval, which will probably come in 2017.

Competition looms

If the Stivarga data do prompt a move into first-line use Bayer must keep an eye on two ongoing HCC studies in this setting: Eisai’s Reflect trial of Lenvima is to render results in December, while Bristol’s CheckMate-459 study of Opdivo is projected to report in May 2017.

Lenvima has shown very strong early results, with a median time to progression of 7.4 months and a median OS of 18.7 months in a single-arm phase I/II trial. At the recent Asco meeting Bristol presented updated findings from its phase II Checkmate-040 study, which showed a 15% overall response rate.

It also reported preliminary data from a dose expansion in 206 HCC patients, which showed an ORR of 9%, with 14% in non-HCV/HBV infected Nexavar-naive/intolerant patients, and 7% in uninfected Nexavar progressors.

Phase III trials in advanced hepatocellular carcinoma
Project Company Trial name Design Trial ID  Data due
Localised first line
Therasphere  BTG Yes-P vs Nexavar NCT01887717 Jun 2019
Therasphere  BTG Stop-HCC Nexavar +/- NCT01556490 Jul 2019
First line
Cometriq Exelixis Celestial  vs placebo NCT01908426 Oct 2016
Lenvima Eisai Reflect vs Nexavar NCT01761266 Dec 2016 
Opdivo  BMS CheckMate 459 vs Nexavar NCT02576509 May 2017
Pexastimogene devacirepvec Sillagen/Transgene Phocus Nexavar +/- NCT02562755 Oct 2017
Donafenib Suzhou Zelgen - vs Nexavar NCT02645981 Dec 2018
Second line
Tivantinib  Daiichi Sankyo/Arqule Metiv-HCC vs placebo NCT01755767 Dec 2016
Tivantinib  Kyowa Hakko Kirin Jet-HCC vs placebo NCT02029157 Dec 2016
Apatinib Jiangsu HengRui - vs placebo NCT02329860 Jan 2017
Livatag Onxeo  Relive vs BSC NCT01655693 Jul 2017
Cyramza Lilly  Reach-2 vs placebo NCT02435433 Oct 2017

As such a possible move of Stivarga to the first-line setting has benefits and risks for Bayer, but there are also perils from not doing anything. There are two agents in pivotal studies for second-line HCC that are due to read out this year: Exelixis’s Cometriq and Arqule’s tivantinib.

Exelixis will be looking to gain an additional indication for Cometriq after its recent success in renal cell carcinoma, while Arqule and its partners Kyowa Hakko Kirin and Daiichi Sankyo are targeting patients with high c-met.

EP Vantage had forecast that progress would come in the HCC field just a few months ago (Hopes rise for a liver cancer breakthrough in 2016, February 19, 2016). Perhaps more will follow. 

To contact the writer of this story email Robin Davison at robind@epvantage.com or follow @RobinDavison2 on Twitter

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