REFLECT is a positive, head-to-head, phase 3 trial vs sorafenib in first-line unresectable HCC1,2
A large, phase 3, multicenter, randomized, open-label, noninferiority trial1-3
- aEligible patients had unresectable HCC, with diagnoses confirmed histologically or cytologically, or confirmed clinically in accordance with American Association for the Study of Liver Diseases criteria.3
- bIneligible for local liver-directed therapy.1
- The REFLECT trial included 217 patients (23%) with hepatitis C and 479 patients (50%) with hepatitis B2
- Patients with ≥50% liver occupation, obvious bile duct invasion, or main portal vein invasion were excluded from the trial2
- The primary endpoint, OS, was tested for noninferiority1
- mRECIST and RECIST version 1.1 were used for independent assessment of PFS and ORR. Secondary endpoints were tested for superiority2
- REFLECT excluded patients who had a gastrointestinal bleeding event or active hemoptysis within 28 days prior to randomization3
mRECIST for HCC criteria measure the sum of viable (enhancement in the arterial phase) tumor diameters and may more accurately measure response in HCC liver lesions than RECIST 1.14,5
REFLECT=A Multicenter, Randomized, Open-Label, Phase 3 Trial to Compare the EFficacy and Safety of LEnvatinib (E7080) Versus Sorafenib in First-Line Treatment of Subjects With UnreseCtable HepaTocellular Carcinoma; HCC=hepatocellular carcinoma; ECOG PS=Eastern Cooperative Oncology Group performance status; BCLC=Barcelona Clinic Liver Cancer; MPVI=macroscopic portal vein invasion; EHS=extrahepatic spread; QD=once daily; BID=twice daily; OS=overall survival; PFS=progression-free survival; ORR=objective response rate; mRECIST=modified Response Evaluation Criteria In Solid Tumors; RECIST=Response Evaluation Criteria In Solid Tumors.
Baseline patient characteristics2
ECOG PS=Eastern Cooperative Oncology Group performance status; PVl=portal vein invasion; EHS=extrahepatic spread; AFP=alpha-fetoprotein; BCLC=Barcelona Clinic Liver Cancer.
- aBased on 471 and 463 patients in the LENVIMA and sorafenib arms, respectively.
- bOne patient had no baseline target lesion.
Classification of macroscopic portal vein invasion (PVI) in REFLECT
Macroscopic PVI is classified according to the site of tumor thrombus6*
Patients with macroscopic PVI Vp1-3 were allowed to be enrolled in REFLECT.3 Patients were stratified by the presence or absence of macroscopic PVI1
Vp1, presence of a tumor thrombus distal to, but not in, the second-order branches of the portal vein6
Vp2, presence of a tumor thrombus in the second-order branches of the portal vein6
Vp3, presence of a tumor thrombus in the first-order branches of the portal vein6
Patients with macroscopic PVI at the main portal branch (Vp4) were excluded from REFLECT per JSH-LCSGJ consensus-based treatment algorithm3,7
Vp4, presence of a tumor thrombus in the main trunk or both first-order branches of the portal vein6
REFLECT=A Multicenter Randomized, Open-Label, Phase 3 Trial to Compare the EFficacy and Safety of LEnvatinib (E7080) Versus Sorafenib in First-Line Treatment of Subjects With UnreseCtable HepaTocellular Carcinoma; JSH-LCSGJ=Japan Society of Hepatology-Liver Cancer Group of Japan.
- *Classification of macroscopic PVI per JSH-LCSGJ.
Assessing antitumor activity (mRECIST for HCC and RECIST 1.1)5,8
mRECIST for HCC and RECIST 1.1
- mRECIST for HCC has introduced specific amendments to RECIST version 1.1 to address the unique complexities involved in the evaluation of tumor response in HCC
- mRECIST for HCC measures the longest viable tumor diameter in the arterial phase of contrast-enhanced imaging
mRECIST for HCC measures the longest viable tumor diameter5
| mRECIST for HCCa | |
| CR | Disappearance of any intratumoral arterial enhancement in all target legions |
| PR | ≥30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions |
| PD | ≥20% increase in the sum of diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started |
RECIST 1.1 measures the longest overall tumor diameter5
| RECIST 1.1 | |
| CR | Disappearance of all target legions |
| PR | ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of the diameters of target lesions |
| PD | ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started. The sum must also demonstrate an absolute increase of at least 5 mm |
| mRECIST for HCCa | RECIST 1.1 | |
| CR | Disappearance of any intratumoral arterial enhancement in all target legions | Disappearance of all target legions |
| PR | ≥30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions | ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of the diameters of target lesions |
| PD | ≥20% increase in the sum of diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started | ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started. The sum must also demonstrate an absolute increase of at least 5 mm |
mRECIST=modified Response Evaluation Criteria in Solid Tumors; HCC=hepatocellular carcinoma; RECIST=Response Evaluation Criteria In Solid Tumors; CR=complete response; PR=partial response; PD=progressive disease.
- aTarget lesions measured by mRECIST are confined to the liver.