Liver cancer is the 3rd leading cause of cancer death worldwide;10 less than half of patients with unresectable HCC are still alive 1 year after diagnosis.11,12
Since 2017, new systemic therapies for advanced HCC have become available, resulting in a major paradigm shift in the treatment pathway.13
TECENTRIQ + bevacizumab was the first systemic combination to show prolonged HCC survival since the approval of sorafenib in 2007, setting a new 1L median OS benchmark of 19 months – a breakthrough in HCC management.13
It is now considered a standard-of-care (SOC) for 1L systemic therapy of unresectable HCC1,7,9 and marks a new era for Immune checkpoint inhibitor-based combination therapies.13
For over a decade, systemic therapy for 1L HCC has shown limited survival benefit and has impacted patient QoL.
TECENTRIQ + bevacizumab, the first cancer immunotherapy combination in 1L unresectable HCC, is revolutionizing the treatment paradigm and bringing new hope to patients.7,14-16
TECENTRIQ, in combination with bevacizumab, is indicated for the treatment of adult patients with advanced or unresectable HCC who have not received prior systemic therapy.14
A global, open-label, Phase III, randomized trial in patients with previously untreated, unresectable HCC7
Patients received IV infusions of TECENTRIQ 1200 mg q3w and bevacizumab 15 mg/kg q3w on Day 1 of each 21-day cycle. Sorafenib was administered orally, 400 mg twice daily, on Days 1 to 21 of each 21-day cycle. Randomization was stratified by geographic region (Asia excluding Japan vs rest of world), macrovascular invasion and/or extrahepatic spread (presence vs absence), baseline AFP (<400 vs ≥400 ng/mL), and ECOG performance status (0 vs 1). The randomization stratification factors were applied to all stratified efficacy analyses except ECOG performance.
*In ITT population. †Assessed by IRF per RECIST v1.1. ‡Assessed by IRF per RECIST v1.1 and HCC mRECIST.
1L, first line; AFP, alpha-fetoprotein; ECOG, Eastern Cooperative Oncology Group; HCC mRECIST, hepatocellular carcinoma modified Response Evaluation Criteria In Solid Tumors; IRF, independent review facility; ITT, intent to treat; IV, intravenous; mHCC, metastatic hepatocellular carcinoma; q3w, every 3 weeks; RECIST, Response Evaluation Criteria In Solid Tumors.
TECENTRIQ + bevacizumab provides durable efficacy for your 1L HCC patients, with a significant OS benefit (34% reduction in risk of death) vs sorafenib8
Clinical cutoff: August 31, 2020; median follow-up: 15.6 months
a: P-value for descriptive purposes only.
CI, confidence interval; HR, hazard ratio; NE, not estimatable; PFS, progression-free survival.
TECENTRIQ + bevacizumab provides durable efficacy, with the longest progression-free survival outcome reported in a global Phase III trial8
TECENTRIQ + bevacizumab demonstrated a median PFS of 6.9 months, compared with 4.3 months following sorafenib8
Clinical cutoff: August 31, 2020; median follow-up: 15.6 months
a: P-value for descriptive purposes only.
CI, confidence interval; HR, hazard ratio; NE, not estimatable; PFS, progression-free survival.
TECENTRIQ + bevacizumab provides the greatest Overall Response Rate (ORR) reported in global Phase III trial, with almost three times the ORR and double the partial response rate observed with sorafenib8
TECENTRIQ + bevacizumab reduced tumor burden vs sorafenib and have demonstrated a disease control rate (objective response or stable disease) of 74% compared with 55% with sorafenib8
*Assessed by IRF per RECIST v1.1.
ORR as assessed by RECIST v1.1 was 30% with TECENTRIQ + bevacizumab (n=97/326; 95% CI, 25–35) vs 11% with sorafenib (n=18/159; 95% CI, 7–17)
At the time of analysis, CCOD: 31 August 2020, median DoR was 18.1 month with TECENTRIQ + bevacizumab (95% CI, 14.6–NE) vs 14.9 months with sorafenib (95% CI, 4.9–17.0).
1L, first line; CCOD, clinical cutoff date; CI, confidence interval; CR, complete response; DCR, disease control rate; DoR, duration of response; IRF, independent review facility; ORR, overall response rate; PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease.
TECENTRIQ + bevacizumab significantly improved OS and PFS vs sorafenib7
Median OS was a coprimary endpoint
CI, confidence interval; HR, hazard ratio; NE, not estimatable; OS, overall survival.
Survival curves separated early, with a median PFS of 6.8 months and 41% reduction in disease progression or death vs sorafenib7
Median PFS as assessed by IRF per RECIST v1.1 was a coprimary endpoint
1L, first line; CI, confidence interval; HR, hazard ratio; IRF, independent review facility; NE, not estimatable; PFS, progression-free survival, RECIST, Response Evaluation Criteria in Solid Tumors.
TECENTRIQ + bevacizumab reduced tumor burden vs sorafenib and have demonstrated a disease control rate (objective response or stable disease) of 74% compared with 55% with sorafenib7
*Assessed by IRF per RECIST v1.1.
ORR as assessed by RECIST v1.1 was 30% with TECENTRIQ + bevacizumab (n=97/326; 95% CI, 25–35) vs 11% with sorafenib (n=18/159; 95% CI, 7–17)
At the time of analysis, CCOD: 31 August 2020, median DoR was 18.1 month with TECENTRIQ + bevacizumab (95% CI, 14.6–NE) vs 14.9 months with sorafenib (95% CI, 4.9–17.0).
1L, first line; CCOD, clinical cutoff date; CI, confidence interval; CR, complete response; DCR, disease control rate; DoR, duration of response; IRF, independent review facility; ORR, overall response rate; PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease.
Pre-specified secondary endpoint that was not formally tested.
*TTD defined as first decrease from baseline of ≥10 points on the EORTC QLQ-C30 maintained for two consecutive assessments or one assessment followed by death from any cause within 3 weeks.
CI, confidence interval; EORTC QLQ, EORTC Quality of Life Questionnaire; HR, hazard ratio; NE, not estimatable; QoL, quality of life; TTD, time to deterioration.
Listen to Dr. David J. Pinato, Imperial College London, UK
Listen to Dr. David J. Pinato and Prof. Amit Singal
Patients with cirrhosis are at risk of upper gastrointestinal bleeding of variceal and nonvariceal origin, with portal hypertension associated with a high risk of gastroesophageal varices.20
Patients with unresectable HCC are at particular risk of gastrointestinal bleeding, estimated at 5–15% per year and related to the size of the varices. This may be exacerbated by treatments that include antiangiogenic agents.
Understanding the safety and AE management profiles of antiangiogenic-based combinations, such as atezolizumab plus bevacizumab, is necessary to support appropriate clinical decision making.20
In clinical practice, patients with cirrhosis (particularly those with portal hypertension) should undergo upper endoscopy to assess their bleeding risk. This is recommended before starting treatment with TECENTRIQ + bevacizumab.20
In the absence of high-risk varices, or where varices have been adequately treated, trial data suggest that patients may benefit from TECENTRIQ + bevacizumab.20
TECENTRIQ + bevacizumab is recognized as a standard of care for 1L unresectable HCC across major treatment guidelines, demonstrating superior efficacy to sorafenib, and with an accepted risk: benefit profile across a broad range of patients.1-6 TECENTRIQ + bevacizumab has been approved in more than 100 countries, with more regulatory authorities performing licensing reviews.22
Listen to Prof. Lorenza Rimassa and Prof. Jörg Trojan
“We can summarize the value of atezolizumab + bevacizumab for patients with advanced HCC in three words: efficacy, safety, and quality of life. Atezolizumab + bevacizumab provides improved efficacy, a good safety profile, and an improved quality of life.”
Atezolizumab + bevacizumab is an effective and safe 1L therapy for advanced-stage HCC in Real-World clinical practice
India
Safety and Efficacy of Atezolizumab-Bevacizumab in Real World: The First Indian Experience
‘Atezolizumab-bevacizumab is safe and effective in uHCC in real-world settings[…]survival and response to therapy are dependent on the severity of liver disease’23
Germany
Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: Results from a German real-world cohort
‘Atezolizumab plus bevacizumab showed good efficacy and safety in patients with unresectable HCC and partially advanced liver cirrhosis in a real-world setting’24
Japan
Comparative efficacy and safety of atezolizumab and bevacizumab between hepatocellular carcinoma patients with viral and non-viral infection: A Japanese multicenter observational study
‘Atezolizumab/bevacizumab had good efficacy and safety for HCC patients with non-viral infection as well as those with viral infection – underlying liver diseases did not affect the clinical outcome of Atezolizumab/bevacizumab treatment’25
International
Reproducible safety and efficacy of atezolizumab plus bevacizumab for HCC in clinical practice: Results of the AB-real study
‘This global observational study confirms the reproducible safety and efficacy of atezolizumab plus bevacizumab in routine clinical practice’26
Watch the videos of international experts examining real-world clinical practice and discussing the value of a multidisciplinary approach for HCC management
Listen to Prof. Lorenza Rimassa and Prof. Peter R. Galle
● The importance of endoscopy in patients presenting with HCC
● The risk of bleeding in patients with varices
● Treatment plans with the hepatologist and treating varices prior to initiation of therapy
● The importance of monitoring patients with varices regularly
● The use of TECENTRIQ® + bevacizumab in HCC patients with varices
Listen to Prof. Lorenza Rimassa and Prof. Bruno Sangro
● Experiences of treating high-risk HCC patients with Vp4
● Important aspects to be considered in your daily practice when treating high-risk HCC patients
● High-risk patients deserve to be treated as much as low-risk patients, and therapy should be based on available clinical and real-world data
● The use of TECENTRIQ® + bevacizumab in high-risk patients with Vp4
Listen to Prof. Ahmed Kaseb and Prof. Jörg Trojan
● Overview of treating patients in the Real World
● Identify which treatment regimen is suited for your patient
● Consider how to appropriate sequence treatment to maximize control of tumors while also improving patient QoL
● HCPs share feedback from their unresectable HCC patients about their treatment experience with 1L atezolizumab + bevacizumab
● Daily life activity is maintained since starting treatment
Listen to Prof. Ahmed Kaseb and Prof. Jörg Trojan
● Overview of the value and benefits of liver patient management via a multidisciplinary team
● Importance of access to all key clinicians when considering management of a new patient to determine eligibility for transplant, tumor resection, radiation, or systemic treatment
● Involvement of a liver MDT improves patient outcomes compared with alternative care routes
● MDTs have a critical role across both early and advanced stage disease, providing quick and effective curative strategies in early disease, and avoidance of unsuitable therapies in advanced disease
Listen to Dr. Peter R. Galle, University Medical Center Mainz, Germany
● 65 years old, male, Chronic HBV with no liver cirrhosis. Diagnosis of HCC with pulmonary and lymph node metastases
● Evaluation and inclusion in the IMbrave150 trial
● Initiated TECENTRIQ + bevacizumab, presents Grade 2 rash but reaches partial response
● Suffers a stroke: Left hemiplegia, Dysarthria, Intracranial hemorrhage
● In follow-up brain scan, confirmation of two new brain metastases. Following the cerebral complications, discontinue bevacizumab and continue with TECENTRIQ
Listen to Dr. Han Chong Toh, National Cancer Centre, Singapore
● 80 years old, male, HBV+, treated with antivirals, hypertensive, treated with single anti-hypertensive agent, fatty liver. Diagnosed with rim-enhancing lesion and multiple bilateral pulmonary metastases
● Initiation of TECENTRIQ + bevacizumab. Scan showed stable hypervascular liver nodule. Multiple lung metastases smaller and one stable lung nodule has increased solid component
● Patient presents Grade 3 hypertension and mild fatigue. If hypertension is not medically controlled, bevacizumab should be withheld and resumed once hypertension is controlled
● After 34 cycles TECENTRIQ + bevacizumab was tolerated well. Patient developed Grade 3 proteinuria and had to omit his latest bevacizumab but continued with TECENTRIQ
Listen to Dr. Vincent Tam, University of Calgary, Canada
● 60 years old, female, history of HCV and liver cirrhosis. Presented severe abdominal pain to the Emergency Department and an MRI abdomen diagnosed HCC
● Hepatologist discussed the case at hepatobiliary MDT rounds and the interventional radiologists (IRs) suggested TACE which was completed and resulted in a complete response
● 3 months later there was recurrent growing tumor in segment VII and V; AFP. A second TACE was suggested and completed. Repeat MRI showed partial response but nodular enhancing tissue was still present
● The case was discussed again at HPB MDT rounds and systemic therapy with TECENTRIQ + bevacizumab was recommended
● An ultrasound-guided biopsy was performed and confirmed HCC. Hepatologist was asked to perform an EGD and band the esophageal varices
● She received TECENTRIQ + bevacizumab and after 3 months (4 cycles) had a decrease in size and enhancement of the nodular enhancing HCC tissue with stability of the new (AFP decreased to 155 ng/mL)
● The patient tolerated TECENTRIQ + bevacizumab well. She developed cold intolerance and was found to be hypothyroid (Grade 2) after 4 cycles where her TSH was 72 mIU/L
● She also developed hypertension with a blood pressure up to 174/102 (Grade 3) and was started on amlodipine 10 mg daily with good effect
● She continues on TECENTRIQ + bevacizumab and has completed 10 cycles
● Last MRI showed the segment IVB HCC had increased to 1.8 cm, with stability of the other HCC lesions (AFP increased to 710 ng/mL)
● Her case will be discussed at HPB MDT rounds again for locoregional treatment options given oligoprogression
Listen to Dr. Michael Morse, Duke Cancer Institute, USA
● Male patient 70 years old with an HCV-related cirrhosis (Gt 4 SVR 2010) and a history of paroxysmal atrial fibrillation and hypercholesterolemia. He was diagnosed with HCC with a 2cm nodule in segment IV
● From 2010 to 2014 he received 4 cycles of RFA. In 2015 he was treated with TACE after recurrence in the left lobe and achieved a complete response. Between 2016 and 2018, the patient received two further ablations. In December 2019, he was found to have diffuse signal abnormality in segments II, IV and VI with indistinct margins (indistinct left lobe infiltrative lesion); his AFP level was 1,754 ng/mL
● No esophageal varices, ascites or encephalopathy and had Child-Pugh class A liver function after evaluation. Initiation of treatment with TECENTRIQ + bevacizumab
● Three cycles of treatment with no headaches, palpitations or heat intolerance. Reasonable appetite and liver function tests were stable. Reported Grade 2 fatigue, and diffuse myalgias in his proximal joints
● After Cycle 4, imaging showed a partial response
● Fatigue subsided and the patient is currently continuing to receive TECENTRIQ + bevacizumab
Listen to Dr. David J. Pinato and Prof. Amit Singal
● For patients with advanced HCC, varices are a common and natural consequence of the portal hypertension associated with progression of cirrhosis.
● Assessment of varices and GI bleeding risk should be undertaken as a standard of care in patients with cirrhosis.
● Risk stratification is very important prior to treatment selection.
● Patients with portal hypertension and significant liver dysfunction are more susceptible to high-risk bleeding events.
● Guidance on delivery of combination immunotherapy enables clinicians to minimize the risk of bleeding in these patients, while maximizing the opportunities for long-term survival.
● Ongoing monitoring of patients with high risk of bleeding is critical.
Listen to Prof. Lorenza Rimassa and Prof. Jörg Trojan
● Summary of clinical experience treating 1L unresectable HCC with atezolizumab + bevacizumab
● Atezolizumab + bevacizumab is now a standard of care for patients who are not candidates for curative therapy
● Treatment is well tolerated, with robust survival benefit
● Benefit associated with a 3-weekly infusion regimen
● Most patients do not experience relevant adverse events
Listen to Dr. David J. Pinato
● Treating with confidence: managing patients on TECENTRIQ + bevacizumab
● How to use TECENTRIQ + bevacizumab in daily clinical practice and what to consider in order to use the combination in clinic and to optimize the patient experience
● HCC patients may present reduced overall mental condition after diagnosis
● Different AEs can have varying degrees of impact on a patient’s physical and emotional wellbeing, especially for skin disorders and fatigue which can significantly affect a patient’s quality of life
● Higher QoL usually comes with longer DoT; such patients will benefit more from the regimen, therefore, it serves the ultimate goal of longer OS
● In the IMbrave150 trial, TECENTRIQ + bevacizumab delayed the time to deterioration of PROs compared with sorafenib
● TECENTRIQ + bevacizumab delayed deterioration of symptoms including appetite loss, diarrhea, fatigue, jaundice and pain, which usually have a significant impact on patients’ daily lives
● Most Grade 3/4 AEs in the TECENTRIQ + bevacizumab arm were usually associated with mild symptoms or are asymptomatic, hypertension, proteinuria or aminotransferase increase
● Sorafenib was more associated with symptomatic AEs: PPE/HFSR and diarrhea with a significant impact on a patient’s quality of life
● The inclusion criteria from the IMbrave150 trial population is a solid foundation when selecting a patient to receive TECENTRIQ + bevacizumab
● HCC patients usually have cirrhosis, a risk factor for the development of esophageal varices, and may lead to rupture and bleeding
● Not every patient needs an endoscopy for varices. If CT indicates splenomegaly or portal hypertension, such high-risk patients will be given an endoscopy. Close monitoring and prediction help to detect early, and intervene
● In the IMbrave150 trial, 26% of patients in each arm had varices at baseline; only 11% of patients treated with TECENTRIQ + bevacizumab had treated varices at baseline
● During treatment with the combination, routine practice should be followed such as liver function monitoring, ultrasound, endoscopy, etc.
● From the safety data of IMbrave150, most bleeding events with TECENTRIQ + bevacizumab were Grade 1 or 2 and manageable. The majority of bleeding events were low-grade. Rates of GI bleeding were low
● There was no difference in Grade 3/4 bleeding events with the combination versus sorafenib (both 6% in each arm) and the overall rate of bleeding events with TECENTRIQ + bevacizumab was also similar to that in the REFLECT trial [Kudo et al. Lancet 2018]
● TECENTRIQ + bevacizumab offers a same-day dosing schedule with consistent 3-weekly infusions. The bevacizumab dose for HCC is 15 mg/kg every 3 weeks, which is similar to many other indications. This is based on dose-escalation studies that showed tolerable safety
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At Roche, we believe in a shared purpose in improving the care and treatment of patients living with difficult to treat cancers. We understand and empathise with the demands you face managing the needs of these patients.
Roche is committed to exploring new treatment options to individualise treatment and meet patients’ needs. TECENTRIQ has proven efficacy as monotherapy as well as in combination with other medicines and we are committed to exploring new combinations to improve patient outcomes (ref. SmPC).
TECENTRIQ is an anti PD-L1 cancer immunotherapy that specifically targets PD-L1 on tumour and tumour-infiltrating immune cells across a broad range of solid tumours. TECENTRIQ offers a pioneering, targeted treatment with proven efficacy and an acceptable tolerability profile (ref. SmPC). Please see the specific indications for more information.
TECENTRIQ has proven efficacy as monotherapy as well as in combination with other medicines and we are committed to explore new combinations for better patient outcomes (ref. SmPC).
In many difficult-to-treat tumour types with a high unmet need, including metastatic urothelial carcinoma, triple negative breast cancer and lung cancer (non-small cell lung cancer and small cell lung cancer), TECENTRIQ has shown significant improvements in progression-free and/or overall survival (ref. SmPC). Importantly, treatment can be tailored (i.e., in combination with the standard of care, or different dosing schedules) according to the type of cancer and the patient’s individual needs (ref. SmPC).
Read SmPC for more details
The multiple indications of TECENTRIQ (ref. SmPC)
provide a wealth of data to inform treatment decision-making and deliver valuable reassurance when considering the needs of your patients with cancer. Please see the specific indications for more information.
TECENTRIQ treatment offers the potential to improve treatment outcomes and maintain patient quality of life in your difficult to treat cancer patients, so they can hopefully spend more time with their loved ones.
TECENTRIQ is approved in metastatic urothelial carcinoma, non-small cell lung cancer, extensive-stage small cell lung cancer and triple negative breast cancer (ref. SmPC).
1L, first line; AE, adverse event; AFP, alpha-fetoprotein; CI, confidence interval; CR, complete response; CT, computed tomography; DCR, disease control rate; DoR, duration of response; DoT, duration of treatment; EORTCQLQ, EORTC Quality of Life Questionnaire; HCC, hepatocellular carcinoma; HFSR, hand-foot skin reaction; HCV, hepatitis C virus; HPB, hepato-pancreato-biliary; HR, hazard ratio; MDT, multidisciplinary team; MRI, magnetic resonance imaging; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PPE, palmar plantar erythrodysesthesia; PR, partial response; SD, stable disease; SoC, standard of care; QoL, quality of life; RECIST, Response Evaluation Criteria in Solid Tumors; RFA, radiofrequency ablation; TACE, transcatheter arterial chemoembolization; TTD, time to deterioration; uHCC, unresectable hepatocellular carcinoma.