Site of Care
The data from the team led by Dr Parikh, culled from a Flatiron Health database of 1965 patients with advanced bladder cancer, came largely from patients who were treated at community centers (94% of those whom were included in the analysis received care at community-based practices).1 “Most patients receive care [at] community oncology sites,” said Dr Parikh, “and so we feel that our study population accurately reflects the real-world population of patients with cancer.”
But prior research has found that the overall survival of patients treated at academic centers tends to be longer than the survival of those who receive care at community oncology centers.8 And in that same study, the receipt of innovative therapies was more likely to occur at an academic center than at a community practice. The adoption of genomics testing at community locations lagged, too, compared with the sequencing uptake seen at large, specialty sites of care.
Prior to the June 2018 mandate from the FDA that narrowed the pool of patients who would be eligible to receive atezolizumab or pembrolizumab to those with PD-L1–positive disease, testing for PD-L1 was not required nor routinely completed in cisplatin-ineligible patients with urothelial carcinoma. In fact, in another study from Flatiron Health, it was found that PD-L1 testing occurred in only 7% of patients with urothelial carcinoma before immunotherapies were distributed.9
The sharp decline in immunotherapy prescribing in UC in 2018 could also have been associated with the increased accessibility of PD-L1 testing. Although the testing for the PD-L1 protein can be performed by different assays, there are 2 tests that interrogate for PD-L1 that are often mentioned in studies of UC: one is the SP142 assay from Roche Diagnostics subsidiary Ventana Medical Systems, Inc., and the other is the PD-L1 IHC 22C3 pharmDx test from Dako North America, Inc., which the FDA approved for use in urothelial carcinoma in August 2018.10
That UC indication added to the scope of the 22C3 device’s existing utility, as it had already been approved to measure PD-L1 in other cancers, including non-small cell lung cancer (NSCLC), gastric/gastroesophageal junction (GEJ) adenocarcinoma, cervical cancer, and most recently, head and neck cancer.11
Although increased competition in the field between players who run these assays could be beneficial, the existence of more than 1 device and testing firm may also introduce some uncertainty surrounding the value and meaning of the PD-L1 score — especially if new research shows that competing tests have discordant results. So far, there are mixed results regarding assay agreement; the results depend on the type of cancer being assayed. It appears that a few of the assays seem to be discordant in the setting of triple-negative breast cancer,12 for example, but appear to have some concordance in the setting of lung cancer.13,14
Disclosure: Most of the authors of the main study featured in this article disclosed ties to the pharmaceutical industry. For a full list of disclosures, please refer to the original JAMA study.
- Parikh RB, Adamson BJS, Khozin S, et al. Association between FDA label restriction and immunotherapy and chemotherapy use in bladder cancer. JAMA. 2019;322(12):1209–1211.
- US Food and Drug Administration. FDA alerts health care professionals and oncology clinical investigators about an efficacy issue identified in clinical trials for some patients taking Keytruda (pembrolizumab) or Tecentriq (atezolizumab) as monotherapy to treat urothelial cancer with low expression of PD-L1. Updated August 16, 2018. Accessed November 22, 2019.
- Nelson R. Oncologists respond rapidly to labeling changes for immunotherapy. Medscape website. Published October 23, 2019. Accessed November 22, 2019.
- Aetna clinical medical policy bulletin. Atezolizumab (Tecentriq). Aetna website. Updated October 15, 2019. Accessed November 22, 2019.
- Aetna clinical medical policy bulletin. Pembrolizumab (Keytruda). Aetna website. Updated August 15, 2019. Accessed November 22, 2019.
- Flaig TW, Spiess PE, Agarwal N, et al. NCCN Guidelines Insights: Bladder Cancer, Version 5.2018. J Natl Compr Canc Netw. 2018;16(9):1041-1053. doi:10.6004/jnccn.2018.0072
- Highmark. Fourth quarter 2018 update: Changes to the Highmark drug formularies. Published October 2018. Accessed November 22, 2019.
- Furlow B. Trials, collaboration might help reduce survival disparities between community, academic cancer centers. Cancer Therapy Advisor website. Published November 15, 2019. Accessed November 22, 2019.
- Felda E, Harton J, Meropol NJ, et al. Effectiveness of first-line immune checkpoint blockade versus carboplatin-based chemotherapy for metastatic urothelial cancer. Eur Urol. 2019;76(4):524-532.
- US Food and Drug Administration. PD-L1 IHC 22C3 pharmDx – P150013/S011. Published August 28, 2018. Accessed November 22, 2019.
- US Food and Drug Administration. PD-L1 IHC 22C3 pharmDx – P150013/S014. Published August 2, 2019. Accessed November 22, 2019.
- Bennett, C. IHC assays for PD-L1 lack concordance in metastatic TNBC. Cancer Therapy Advisor website. Published October 8, 2019. Accessed November 22, 2019.
- Krigsfeld GS, Zerba K, Chizhevsky V, Ragheb JW, White J. Analysis of real-world PD-L1 testing for clinical use in patients with lung cancer. Presented at: 2019 Multidisciplinary Thoracic Cancers Symposium; March 14-16, 2019: San Diego, California. Abstract 100.
- Krigsfeld GS, Zerba K, Novotny J, Chizhevsky V, Ragheb JW, and White J. A comparative study of the PD-L1 IHC 22C3 and 28-8 assays on lung cancer samples. Presented at: 2019 Multidisciplinary Thoracic Cancers Symposium; March 14-16, 2019: San Diego, California. Abstract 101.