Addressing Disparities in Liver Cancer Care to Improve Access to First-Line Treatment for Minority and Underserved Populations with Hepatocellular Carcinoma

Shikha Jain, MD, FACP, discusses disparities in HCC and the need for equitable treatment and care.

While hepatocellular carcinoma (HCC) is the most common form of primary liver cancer¹, it disproportionately impacts certain populations.² These include minorities and underserved communities who face unique socioeconomic, cultural and geographic barriers that may prevent them from accessing quality and timely care.

The disparities are not merely statistical. Shikha Jain, MD, FACP, associate professor of medicine, division of hematology and oncology, GI oncology integrated practice unit lead and director of communication strategies in medicine, University of Illinois (UI) Chicago, associate director of oncology communication & digital Innovation, UI Cancer Center, discusses how they have profound implications for patient outcomes and treatment efficacy—presenting both a challenge and an opportunity for healthcare providers to improve care.

Understanding the Impact of Disparities

In the U.S., liver cancer incidence rates are approximately 1.5 to 2 times higher in American Indian or Alaska Native, Asian, Black and Latino populations than in White populations.³ But even within broad racial or ethnic categories, there are important distinctions to understand.

“To address healthcare disparities and ensure equitable care, it's essential to avoid grouping patients into broad categories that overlook individual diversity," explains Dr. Jain. "For instance, a 'Latin American patient' could be someone with Mexican, Venezuelan, or Chilean heritage, each with unique experiences. Similarly, Black patients, whether immigrants from Nigeria or born in the U.S., face distinct challenges. Recognizing this diversity is crucial for addressing healthcare disparities and providing truly equitable care."

This nuance is crucial because a one-size-fits-all approach is insufficient when addressing the needs of diverse patient populations. Adopting a more holistic approach to care may help reduce disparities. This includes understanding the cultural and socioeconomic contexts of patients and advocating for more inclusive practices in clinical trials.

“Many of the trials have less than 5% Black and Hispanic patients,” Dr. Jain points out. “We’re really at a disadvantage because we don’t know if the biology or pathophysiology are the same.”

By advocating for more inclusive research practices, healthcare providers can help to ensure groundbreaking therapies like Tecentriq (atezolizumab) plus Avastin (bevacizumab), approved for the treatment of first-line unresectable or metastatic hepatocellular carcinoma (mHCC), are accessible for patients with certain types of liver cancer.

Improving the Standard of Care with Tecentriq + Avastin

The availability of Tecentriq plus Avastin has brought significant progress in managing unresectable or mHCC. Approved in 2020, this combination treatment was the first and only cancer immunotherapy (CIT) approved for mHCC that demonstrated superior overall survival and progression-free survival compared to the previous standard of care, sorafenib.⁴ The approval was based on results from the Phase III IMbrave150 study, which demonstrated that the immunotherapy combination reduced the risk of death (overall survival; OS) by 42% (hazard ratio [HR]=0.58; 95% CI: 0.42-0.79; p=0.0006) and reduced the risk of disease worsening or death (progression-free survival; PFS) by 41% (HR=0.59; 95% CI: 0.47-0.76; p<0.0001), compared with sorafenib.⁴ In this study, 38% of patients on the Tecentriq plus Avastin regimen experienced serious adverse reactions.⁴

Select Important Safety Information: Serious and sometimes fatal adverse reactions occurred with TECENTRIQ treatment. Warnings and precautions include severe and fatal immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, endocrinopathies, dermatologic adverse reactions, nephritis with renal dysfunction, and solid organ transplant rejection. Other warnings and precautions include infusion-related reactions, complications of allogeneic HSCT, and embryo-fetal toxicity.

Please see additional Important Safety Information in the full Prescribing Information and below.

For many clinicians, including Dr. Jain, they choose to prescribe this first line (1L) treatment option for mHCC.*⁵ “I usually start with atezolizumab (Tecentriq) and bevacizumab (Avastin) if that patient doesn’t have varices or if they have varices that are controlled,” Dr. Jain states. “It’s been around for a while in the cancer world and I found that it’s fairly well tolerated.”

While Tecentriq plus Avastin could benefit many patients, there are barriers that prevent patients from getting treatment. Socioeconomic factors, such as lack of insurance or the inability to take time off work, often prevent patients from receiving care.

Dr. Jain recounts a case that starkly illustrates this issue: “I had a patient who needed to be admitted for HCC. I told him ‘you are going to die if we do not admit you.’ He refused to get admitted because he thought he was going to lose his job,” she recalls. “So I ended up getting on the phone with a translator, the patient and his boss to explain the situation. Ultimately, we ended up getting him admitted to the hospital.”

Such stories underscore the importance of open communication between healthcare providers and patients. “I think as HCPs, we need to really spend that time to figure out why the patient didn’t come, instead of labeling them as non-compliant. Maybe they didn’t have a ride. Maybe they were scared,” Dr. Jain says.

While access and clinical factors are important, it’s up to the decision of the provider to use the guideline-recommended treatments and participate in clinical trials. Addressing these factors is essential to ensure that all patients receive the appropriate care and have equal opportunities to benefit from advanced treatments.

Moving Toward More Equitable Care

As a standard of care in 1L mHCC, Tecentriq plus Avastin may provide an important treatment option for patients. However, to truly make an impact, it’s vital to address the disparities that prevent many patients from accessing this treatment, which includes increasing access to care, ensuring clinical trials are representative of the populations they aim to serve and prioritizing patient-centered communication.

By embracing this responsibility, healthcare providers can help close the gap in liver cancer care and move toward a more equitable healthcare system. As Dr. Jain aptly states, “It’s our job to communicate openly with these patients as much as we can.”

*Based on Flatiron EMR dating ending in Q4 ‘23

Indication
TECENTRIQ, in combination with bevacizumab, is indicated for the treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy.

Important Safety Information
Severe and Fatal Immune-Mediated Adverse Reactions
TECENTRIQ is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. The following immune-mediated adverse reactions may not include all possible severe and fatal immune-mediated reactions.

Immune-mediated adverse reactions can occur in any organ system or tissue and at any time after starting TECENTRIQ. While immune-mediated adverse reactions usually manifest during treatment with TECENTRIQ, they can also manifest after discontinuation of treatment. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of TECENTRIQ.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue TECENTRIQ depending on severity. In general, if TECENTRIQ requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less, then initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

• TECENTRIQ can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation
• Immune-mediated pneumonitis occurred in 3% (83/2616) of patients receiving TECENTRIQ alone, including fatal (<0.1%), Grade 4 (0.2%), Grade 3 (0.8%), and Grade 2 (1.1%) adverse reactions. Pneumonitis led to permanent discontinuation of TECENTRIQ in 0.5% and withholding of TECENTRIQ in 1.5% of patients
• Systemic corticosteroids were required in 55% (46/83) of patients with pneumonitis. Pneumonitis resolved in 69% of the 83 patients. Of the 39 patients in whom TECENTRIQ was withheld for pneumonitis, 25 reinitiated TECENTRIQ after symptom improvement; of these, 4% had recurrence of pneumonitis

Immune-Mediated Colitis

• TECENTRIQ can cause immune-mediated colitis. Colitis can present with diarrhea, abdominal pain, and lower gastrointestinal (GI) bleeding. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies
• Immune-mediated colitis occurred in 1% (26/2616) of patients receiving TECENTRIQ alone, including Grade 3 (0.5%) and Grade 2 (0.3%) adverse reactions. Colitis led to permanent discontinuation of TECENTRIQ in 0.2% and withholding of TECENTRIQ in 0.5% of patients. Systemic corticosteroids were required in 50% (13/26) of patients with colitis. Colitis resolved in 73% of the 26 patients. Of the 12 patients in whom TECENTRIQ was withheld for colitis, 8 reinitiated TECENTRIQ after symptom improvement; of these, 25% had recurrence of colitis

Immune-Mediated Hepatitis

• TECENTRIQ can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 1.8% (48/2616) of patients receiving TECENTRIQ alone, including fatal (<0.1%), Grade 4 (0.2%), Grade 3 (0.5%), and Grade 2 (0.5%) adverse reactions. Hepatitis led to permanent discontinuation of TECENTRIQ in 0.2% and withholding of TECENTRIQ in 0.2% of patients. Systemic corticosteroids were required in 25% (12/48) of patients with hepatitis. Hepatitis resolved in 50% of the 48 patients. Of the 6 patients in whom TECENTRIQ was withheld for hepatitis, 4 reinitiated TECENTRIQ after symptom improvement; of these, none had recurrence of hepatitis

Immune-Mediated Endocrinopathies
Adrenal Insufficiency

• TECENTRIQ can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated
• Adrenal insufficiency occurred in 0.4% (11/2616) of patients receiving TECENTRIQ alone, including Grade 3 (<0.1%) and Grade 2 (0.2%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of TECENTRIQ in 1 patient and withholding of TECENTRIQ in 1 patient. Systemic corticosteroids were required in 82% (9/11) of patients with adrenal insufficiency; of these, 3 patients remained on systemic corticosteroids. The single patient in whom TECENTRIQ was withheld for adrenal insufficiency did not reinitiate TECENTRIQ

Hypophysitis

• TECENTRIQ can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated
• Hypophysitis occurred in <0.1% (2/2616) of patients receiving TECENTRIQ alone, including Grade 2 (1 patient, <0.1%) adverse reactions. Hypophysitis led to permanent discontinuation of TECENTRIQ in 1 patient and no patients required withholding of TECENTRIQ. Systemic corticosteroids were required in 50% (1/2) of patients with hypophysitis. Hypophysitis did not resolve in these 2 patients

Thyroid Disorders

• TECENTRIQ can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or medical management for hyperthyroidism as clinically indicated
• Thyroiditis occurred in 0.2% (4/2616) of patients receiving TECENTRIQ alone, including Grade 2 (<0.1%) adverse reactions. Thyroiditis did not lead to permanent discontinuation of TECENTRIQ in any of these patients, but led to withholding of TECENTRIQ in 1 patient. Hormone replacement therapy was required in 75% (3/4) of patients with thyroiditis. Systemic corticosteroids were required in 25% (1/4) of patients with thyroiditis. Thyroiditis resolved in 50% of patients. The single patient in whom TECENTRIQ was withheld for thyroiditis reinitiated TECENTRIQ; this patient did not have recurrence of thyroiditis
• Hyperthyroidism occurred in 0.8% (21/2616) of patients receiving TECENTRIQ alone, including Grade 2 (0.4%) adverse reactions. Hyperthyroidism did not lead to permanent discontinuation of TECENTRIQ in any of these patients, but led to withholding of TECENTRIQ in 0.1% of patients. Antithyroid therapy was required in 29% (6/21) of patients with hyperthyroidism. Of these 6 patients, the majority remained on antithyroid treatment. Of the 3 patients in whom TECENTRIQ was withheld for hyperthyroidism, 1 patient reinitiated TECENTRIQ; this patient did not have recurrence of hyperthyroidism
• Hypothyroidism occurred in 4.9% (128/2616) of patients receiving TECENTRIQ alone, including Grade 3 (0.2%) and Grade 2 (3.4%) adverse reactions. Hypothyroidism did not lead to permanent discontinuation of TECENTRIQ in any of these patients, but led to withholding of TECENTRIQ in 0.6% of patients. Hormone replacement therapy was required in 81% (104/128) of patients with hypothyroidism. The majority of patients with hypothyroidism remained on thyroid hormone replacement. Of the 17 patients in whom TECENTRIQ was withheld for hypothyroidism, 8 reinitiated TECENTRIQ after symptom improvement

Type 1 Diabetes Mellitus, Which Can Present With Diabetic Ketoacidosis

• Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated
• Type 1 diabetes mellitus occurred in 0.3% (7/2616) of patients receiving TECENTRIQ alone, including Grade 3 (0.2%) and Grade 2 (<0.1%) adverse reactions. Type 1 diabetes mellitus led to permanent discontinuation of TECENTRIQ in 1 patient and withholding of TECENTRIQ in 2 patients. Treatment with insulin was required for all patients with confirmed Type 1 diabetes mellitus and insulin therapy was continued long-term. Of the 2 patients in whom TECENTRIQ was withheld for Type 1 diabetes mellitus, both reinitiated TECENTRIQ treatment

Immune-Mediated Nephritis With Renal Dysfunction

• TECENTRIQ can cause immune-mediated nephritis
• Immune-mediated nephritis with renal dysfunction occurred in <0.1% (1/2616) of patients receiving TECENTRIQ alone, and this adverse reaction was a Grade 3 (<0.1%) adverse reaction. Nephritis led to permanent discontinuation of TECENTRIQ in this patient. This patient required systemic corticosteroids. In this patient, nephritis did not resolve

Immune-Mediated Dermatologic Adverse Reactions

• TECENTRIQ can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), DRESS, and toxic epidermal necrolysis (TEN), has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes
• Immune-mediated dermatologic adverse reactions occurred in 0.6% (15/2616) of patients receiving TECENTRIQ alone, including Grade 3 (<0.1%) and Grade 2 (0.2%) adverse reactions. Dermatologic adverse reactions led to permanent discontinuation of TECENTRIQ in 0.1% and withholding of TECENTRIQ in 0.2% of patients. Systemic corticosteroids were required in 20% (3/15) of patients with dermatologic adverse reactions. Dermatologic adverse reactions resolved in 87% of the 15 patients. Of the 4 patients in whom TECENTRIQ was withheld for immune-mediated dermatologic adverse reactions, none reinitiated TECENTRIQ

Other Immune-Mediated Adverse Reactions

• The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received TECENTRIQ or were reported with the use of other PD-1/PD-L1 blocking antibodies

- Cardiac/Vascular: Myocarditis, pericarditis, vasculitis
- Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy
- Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss
- Gastrointestinal: Pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis
- Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic
- Endocrine: Hypoparathyroidism
- Other (Hematologic/Immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection

Infusion-Related Reactions

• TECENTRIQ can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue TECENTRIQ based on the severity. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses
• Infusion-related reactions occurred in 1.3% of patients receiving TECENTRIQ alone, including Grade 3 (0.2%) reactions
• The frequency and severity of infusion-related reactions were similar across the recommended dose range

Complications of Allogeneic HSCT After PD-1/PD-L1 Inhibitors

• Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody
• Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause)
• These complications may occur despite intervening therapy between PD-1/PD-L1 blockage and allogeneic HSCT
• Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefits versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT

Embryo-Fetal Toxicity

• Based on its mechanism of action, TECENTRIQ can cause fetal harm when administered to a pregnant woman. There are no available data on the use of TECENTRIQ in pregnant women. Animal studies have demonstrated that inhibition of the PD-L1/PD-1 pathway can lead to increased risk of immune-related rejection of the developing fetus, resulting in fetal death
• Verify pregnancy status of females of reproductive potential prior to initiating TECENTRIQ. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment with TECENTRIQ and for at least 5 months after the last dose

Use in Specific Populations
Nursing Mothers

• There is no information regarding the presence of TECENTRIQ in human milk, the effects on the breastfed infant, or the effects on milk production. As human IgG is excreted in human milk, the potential for absorption and harm to the infant is unknown
• Because of the potential for serious adverse reactions in breastfed infants from TECENTRIQ, advise female patients not to breastfeed while taking TECENTRIQ and for at least 5 months after the last dose

Fertility

• Based on animal studies, TECENTRIQ may impair fertility in females of reproductive potential while receiving treatment

Most Common Adverse Reactions
The most common adverse reactions (rate ≥20%) in patients who received TECENTRIQ in combination with bevacizumab for HCC were hypertension (30%), fatigue/asthenia (26%), and proteinuria (20%).

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see full TECENTRIQ Prescribing Information and full Avastin Prescribing Information for additional Important Safety Information.

References

1. American Cancer Society. (2019). What is liver cancer?: Liver cancer types. Liver Cancer Types https://www.cancer.org/cancer/types/liver-cancer/about/what-is-liver-cancer.html
2. Flores, Y. N., Datta, G. D., Yang, L., Corona, E., Devineni, D., Glenn, B. A., Bastani, R., & May, F. P. (2021). Disparities in hepatocellular carcinoma incidence, stage, and survival: A large population-based study. Cancer Epidemiology, Biomarkers &amp; Prevention, 30(6), 1193–1199. https://doi.org/10.1158/1055-9965.epi-20-1088
3. Herren, O. M., Gillman, A. S., Marshall, V. J., & Das, R. (2023). Understanding the changing landscape of health disparities in chronic liver diseases and liver cancer. Gastro Hep Advances, 2(4), 505–520. https://doi.org/10.1016/j.gastha.2022.12.001
4. Genentech. (2020). FDA approved Genentech’s Tecentriq in combination with Avastin and chemotherapy for people with advanced liver cancer. https://www.gene.com/media/press-releases/14856/2020-05-29/fda-approves-genentechs-tecentriq-in-com#:~:text=The%20approval%20was%20based%20on,0.0001
5. Data on file. Genentech, Inc.

M-US-00024594(v2.0)