Ventana PD-L1 (SP142) Assay

US Pharm. 2022;47(10):42-44.

Triple-negative breast cancer (TNBC) occurs when breast cancer (BC) cells test negative for the estrogen and progesterone hormones at their respective receptors and for the human epidermal growth factor receptor 2 protein. In this instance, hormonal treatments and trastuzumab would be ineffective. Manifestations of this cancer include pain, swelling, a lump in the breast, dimpling of the skin, orange-peel skin appearance, nipple discharge, inverted nipple, and skin changes such as redness, hardness, thickening, or flaking.¹ Tecentriq (atezolizumab) in combination with Abraxane (albumin-bound [nab]-paclitaxel) is a human monoclonal antibody that had an FDA-accelerated approval for programmed death-ligand 1 (PD-L1)–positive metastatic TNBC but was withdrawn in August 2021.² It binds to PD-L1 on tumor cells and/or tumor-infiltrating immune cells, which blocks it from binding to the PD-1 and B-7 receptors, resulting in reactivation of antitumor T-cells.¹ However, it is still currently indicated for urothelial carcinoma, non–small cell lung cancer (NSCLC), small cell lung cancer, hepatocellular carcinoma, and melanoma.

Epidemiology and Etiology

TNBC accounts for about 10% to 20% of all BCs worldwide and approximately 200,000 cases per year; it is more prevalent in women aged younger than 40 years and black or African American women.^3,4 Additionally, those who have the inherited BC gene (BRCA1 and lesser common BRCA2 mutations) are at a higher risk for developing TNBC. Lifestyle factors such as lack of physical activity, hormonal therapies, and alcohol consumption play a huge role in the development of TNBC. Lastly, studies have shown that women in a premenopausal status are at a higher risk of developing TNBC, and it is recommended that genetic testing be performed on these individuals. Other factors may include obesity and first pregnancy at a young age.

Ventana PD-L1 (Sp142) Assay Device

The Ventana PD-L1 (SP142) Assay is a qualitative immunohistochemical assay used in evaluating the proportion of tumor area occupied by PD-L1 expressing tumor-infiltrating immune cells (% IC) of any intensity or the percentage of PD-L1 expressing tumor cells (% TC) of any intensity.⁵ This device is not only used in TNBC but also urothelial carcinoma and NSCLC. The device uses a biopsy sample of the patient’s cancerous tissue to test for the presence of this protein at a laboratory. If PD-L1 proteins are present in the slide, it will stain brown, which indicates a positive result as interpreted by a qualified pathologist. Therefore, having a device such as the Ventana PD-L1 (SP142) Assay that specifically tests to determine if the patient has PD-L1-positive cells aids the patient’s physician in the decision to initiate atezolizumab, which is designed to specifically target the cause of their health condition. Furthermore, Tecentriq treatment costs around $13,860 per month depending on the dosage schedule and can be used in TNBC patients who have failed other standard-of-care therapies.⁶

Monitoring

There is a plethora of monitoring tests to determine the breast cancer stage and efficacy of the medication. Some of the exams include—but are not limited to—an ultrasound, mammogram, molecular breast imaging, or a breast MRI.^7,8 There are currently no known contraindications to using the Ventana PD-L1 (SP142) Assay. If a patient is initiated on atezolizumab, the following should be monitored⁹:
• Tumor response rate to indicate efficacy.
• Creatinine, liver enzymes, and thyroid function at baseline and periodically throughout treatment.
• Type 1 diabetes mellitus, which can present with diabetic ketoacidosis, and other signs and symptoms of diabetes.
• Immune-mediated adverse reactions: pneumonitis, colitis, hepatitis, endocrinopathies (e.g., adrenal insufficiency, hypophysitis, thyroiditis, hyper- or hypothyroidism), nephritis with renal dysfunction, solid organ transplant rejection, and dermatologic adverse reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms).
• Pregnancy status prior to initiation in women of reproductive potential.
• Transplant-related complications, such as graft-versus-host disease and veno-occlusive disease, in patients who receive allogeneic hematopoietic stem cell transplantation before or after being treated with a PD-1/PD-L1-blocking antibody.
• Signs and symptoms of infusion-related reactions.
• Any common side effects of atezolizumab.

Efficacy

The IMpassion130 trial was a phase III, international, randomized, double-blind, placebo-controlled trial.¹⁰ A total of 902 patients were enrolled and randomized into a 1:1 ratio to receive atezolizumab plus nanoparticle nab–paclitaxel compared with placebo plus nab-paclitaxel. The trial included patients aged 18 years and older who had metastatic or locally advanced unresectable TNBC to evaluate the primary outcome of progression-free survival and overall survival over a follow-up period of 12.9 months. A tumor specimen was collected and analyzed for PD-L1 expression utilizing the Ventana PD-L1 (SP142) Assay.

Statistically significant data from the IMpassion130 trial showed that treatment using atezolizumab plus nab-paclitaxel resulted in longer progression-free survival rates by a difference of 2.5 months compared with placebo plus nab-paclitaxel (7.5 months vs. 5.0 months, respectively). This clinical trial supported the efficacy of the Ventana PD-L1 (SP142) Assay in evaluating the PD-L1 expression, determination of treatment, and improvement in the overall survival of the patient. The 5-year survival rates for localized TNBC are 91%, regional is 65%, and metastasized is 11%.¹

Conclusion

The FDA-approved medical device, Ventana PD-L1 (SP142) Assay, has tremendously impacted treating TNBC. Based on its demonstration in the IMpassion130 clinical trial, it has shown to be effective in evaluating PD-L1 expression by analyzing a thin portion of the patient’s cancerous tissue. Its high sensitivity and low specificity have allowed it to help physicians determine whether or not Tecentriq will be optimally beneficial for TNBC patients before initiating a costly treatment regimen. Continued usage of the Ventana PD-L1 (SP142) Assay will improve overall mortality caused by TNBC. Additional information about the device can be found online through the FDA.gov website.¹¹

REFERENCES

1. Cancer Treatment Centers of America. Triple-negative breast cancer. June 24, 2022. www.cancercenter.com/cancer-types/breast-cancer/types/rare-breast-cancer-types/triple-negative-breast-cancer. Accessed September 15, 2022.
2. Genentech. Genentech provides an update on Tecentriq U.S. indication for PD-L1-positive, metastatic triple-negative breast cancer. August 27, 2021. www.gene.com/media/press-releases/14927/2021-08-27/genentech-provides-update-on-tecentriq-u. Accessed November 17, 2021.
3. Gierach GL, Burke A, Anderson WF. Epidemiology of triple negative breast cancers. Breast Dis. 2010;32(1-2):5-24.
4. Howard FM, Olopade OI. Epidemiology of triple-negative breast cancer: a review. Cancer J. 2021;27(1):8-16.
5. FDA. Summary of safety and effectiveness data (SSED). www.accessdata.fda.gov/cdrh_docs/pdf16/p160002s009b.pdf. Accessed September 18, 2021.
6. Drugs.com. What is the cost of Tecentriq? May 12, 2022. www.drugs com/medical-answers/cost-tecentriq-3064818/. Accessed September 15, 2022.
7. Breastcancer.org. Screening and testing. www.breastcancer.org/screening-testing. Accessed September 15, 2022.
8. McGarry WM, Bhole S (2018) Triple-negative breast cancer: what crucial information can imaging add to the diagnosis, treatment, and prognosis? Int J Womens Health Wellness. 2018;5(1):087.
9. Tecentriq (atezolizumab) package insert. San Francisco, CA: Genentech, Inc.; 2021.
10. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379(22):2108-2121.
11. FDA. Ventana PD-L1 (SP142) assay-P160002/S009. March 20, 2019. https://public4.pagefreezer.com/browse/FDA/28-01-2022T11:16/https://www.fda.gov/medical-devices/recently-approved-devices/ventana-pd-l1-sp142-assay-p160002s009. Accessed September 15, 2022.

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