Advanced HCC: IMbrave150 Trial

Pierre Gholam, MD: There have more recently been exciting and encouraging studies, encouraging findings, from the IMbrave150 trial. This is a trial whose results were just published in the New England Journal of Medicine. That is a combination of atezolizumab and bevacizumab in the setting of unresectable HCC [hepatocellular carcinoma].

This combination was basically studied in the first line versus sorafenib in a group of 336 patients. The primary outcome was overall survival, and this was met at an interim analysis, which led to the publication of these data. In the spirit of being transparent and reflecting the facts as we know them today, I will say that this combination is currently being studied and analyzed by the FDA and has not received FDA approval in the first line. Nonetheless, the findings from the atezolizumab-bevacizumab study in comparison with sorafenib in a 2-to-1 randomization schema essentially shows an overall survival of 67.2% for atezolizumab-bevacizumab versus 54.6% with sorafenib. Notice that I’m not giving absolute months here because at the time when these data were published, the actual overall survival for the cohorts had not been reached.

The median progression-free survival at the time of censoring of the data that I’m reporting today was 6.8 months for ATEZO-BEV [atezolizumab-bevacizumab] versus 4.3 months for sorafenib. This is additional ammunition, additional good news for patients who are considering therapy in the first line for BCLC stage C disease, which means disease that is typically metastatic to a blood vessel or to outside the liver. Certainly this adds to our potential armamentarium for treatment of these patients, as the NCCN [National Comprehensive Cancer Network] Guidelines have endorsed.

One question would be whether these treatments would be appropriate for patients who have hepatitis B or C depending on how patients fall into the category. The answer is these seem to be appropriate patients for treatment as the overall patient demographic in both the Lenvima (lenvatinib) study, REFLECT, as well as the IMbrave150 trial seemed to include a fair number of these patients with outcomes that are fairly comparable to the overall patient population.

Transcript edited for clarity.

Case: A 61-Year-Old Man with Stage 4 Hepatocellular Carcinoma

Initial presentation

• A 61-year-old man presented with nausea, vomiting, decreased appetite and occasional generalized itching
• PMH: diabetes, medially controlled; hepatitis C and B coinfection diagnosed and treated 6 years ago; diagnosed with HCC December 2018
• PE: scleral icterus; jaundice; spleen palpable 4-cm below the costal margin
  
  

Clinical workup

• Labs: AFP 436 ng/mL, bilirubin 1.6 mg/dL, AST 105 U/L, ALT 110 U/L, ALP 390 U/L, INR 1.9, albumin 3.8 g/dL, BUN 13 mg/dL, creatinine 1 mg/dL, plt 95,000
• HBV+, HCV+
• Abdominal ultrasound revealed 3 small hepatic lesions
• Chest/abdominal/pelvic CT scan confirmed 2 focal nodules in the right and 1 in the left hepatic lobe measuring 3.6 cm, 4.9 cm and 5.2 cm, a suspicious lesion in the right lower lung lobe; wide-spread lymphadenopathy was noted
• Biopsy findings showed grade 3 hepatocellular carcinoma with marked fibrosis
• Surgical consult: unresectable due to tumor size and location
• Child-Pugh A; BCLC stage C
• ECOG 1
  
  

Treatment and Follow-Up

• 2018: treated with lenvatinib 400 mg PO q12hr; he experienced diarrhea for 2 weeks which resolved; achieved PR
• 2020: Imaging showed a new lung lesion
  • Treatment was with cabozantinib 60 mg PO qDay was initiated