Progression Type in HCC Influences Survival Duration

Jordi Bruix, MD

Patients with advanced hepatocellular carcinoma (HCC) had a worse survival following progression if they developed new extrahepatic lesions as opposed to other types of progression, supporting the concept of post-progression survival (PPS) and the influence of different patterns of progression, according to an analysis of the phase III RESORCE trial.¹

Results of the large, randomized, placebo-controlled trial showed that patients with new extrahepatic lesions had a median PPS of 8.2 months with placebo and 9.7 months with regorafenib (Stivarga), the briefest survival interval for either treatment arm. The results also showed that treatment with regorafenib led to better PPS, irrespective of the type of disease progression, Jordi Bruix, MD, head of the Barcelona Clinic Liver Cancer (BCLC) at University of Barcelona, and colleagues reported at the 2017 Gastrointestinal Cancers Symposium.

“This exploratory analysis validates the finding that the pattern of progression influences PPS,” the investigators concluded in a poster presentation. “The development of new extrahepatic lesions was associated with worse survival regardless of treatment, consistent with what has been reported. This exploratory analysis also showed that regorafenib provides an overall survival (OS) benefit, regardless of the pattern of progression on prior sorafenib (Nexavar) treatment.

“Progression pattern may be a key prognostic parameter and should be considered when designing and analyzing future trials.”

Progression of HCC occurs as a result of the growth of known intrahepatic or extrahepatic lesions or from the development of new lesions. Recently, Reig, et al, introduced the concept of PPS, along with 4 categories of progression for patients treated with sunitinib (Sutent).² They categorized progression as formation of new intrahepatic or extrahepatic lesions or growth of known intrahepatic or extrahepatic lesions.

A preliminary analysis of PPS showed that survival varied by type of progression, as determined by radiographic evidence. Additionally, the presence of new extrahepatic lesions emerged as an independent adverse predictor of progression-free survival (PFS) and overall survival (OS).

In an effort to confirm the previous findings and provide support for the concept of PPS, Bruix and colleagues analyzed data from the phase III RESORCE trial, conducted at 152 centers in 21 countries. Investigator enrolled 573 patients with radiographic progression of HCC during treatment with sorafenib. They were randomized 2:1 to regorafenib or placebo and followed until disease progression, death, or development of unacceptable toxicity.

The type of disease progression (new lesions or growth of existing lesions) was confirmed radiographically for all patients. Because of the method of data collection used in the trial, Bruix and colleagues classified disease progression in 1 of 3 ways: new extrahepatic lesion, new intrahepatic lesion, or growth of existing intra- or extrahepatic lesions.

The results showed that approximately 40% of patients had new extrahepatic lesions, 45% had new intrahepatic lesions, and 80% had growth of existing lesions. Some patients had more than 1 type of progression.

The primary outcome of the analysis was PPS after progression on sunitinib. The analysis showed that patients with new intrahepatic lesions had a median PPS of 12.2 months with regorafenib and 10.2 months with placebo (HR, 0.79; 95% CI, 0.58-1.08). Those without new intrahepatic lesions had a median PPS of 12.3 months with regorafenib and 9.5 months with placebo (HR, 0.59; 95% CI, 0.45-0.79).

Presence of new extrahepatic lesions was associated with a median PFS of 9.7 months with regorafenib and 8.2 months with placebo (HR, 0.70; 95% CI, 0.51-0.97), whereas patients without new extrahepatic lesions had a median PPS of 14.7 and 10.5 months with regorafenib and placebo, respectively (HR, 0.65; 95% CI, 0.49-0.85).

Examination of patients who had growth of existing lesions (intra- or extrahepatic) yielded a median PPS of 12.5 months with regorafenib and 9.5 months with placebo (HR, 0.64; 95% CI, 0.50-0.81). Patients without growth of existing lesions had a median PFS of 10.7 months with regorafenib and 9.8 months with placebo (HR, 0.85; 95% CI, 0.53-1.35).

References

1. Bruix J, Merle P, Granito A, et al. Survival by pattern of tumor progression during prior sorafenib (SOR) treatment in patients with hepatocellular carcinoma (HCC) in the phase III RESORCE trial comparing second-line treatment with regorafenib (REG) or placebo. J Clin Oncol. 2017;35 (suppl 4S; abstr 229).
2. Reig M, Rimola J, Torres F, et al. Postprogression survival of patients with advanced hepatocellular carcinoma: Rationale for second-line trial design. Hepatology. 2013;58:2023-2031.

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