Advertisement

Clinical and Patient-Reported Outcomes of Advanced Urothelial Carcinoma Following Discontinuation of PD-1/L1 Inhibitor Therapy

Published:August 05, 2022DOI:https://doi.org/10.1016/j.clgc.2022.08.002

      Highlights

      • An ambispective chart review of patients with la/mUC following PD-1/L1 therapy.
      • Following PD-1/L1 inhibitor discontinuation, only one third received subsequent treatment.
      • OS was longer in patients who received additional therapy following discontinuation of PD-1/L1 inhibitor.
      • Real-world outcomes in patients with la/mUC following PD-1/L1 therapy are poor.

      Abstract

      Introduction

      The patterns of care and attrition of locally advanced or metastatic urothelial carcinoma (la/mUC) patients eligible for systemic therapy following PD-1/L1 inhibitors are unclear. The objective of this study was to evaluate the clinical characteristics and treatment patterns among patients with la/mUC following discontinuation of first-line (1L) or second-line (2L) PD-1/L1 inhibitor therapy.

      Methods

      An ambispective, multisite, chart review study was conducted in the United States, including patients with la/mUC. Eligible patients had initiated and subsequently discontinued PD-1/L1 therapy in the 1L or 2L setting for la/mUC between May 2016–July 2018; with follow-up through October 2019. Patient characteristics, treatments and overall survival (OS) were described. Patients had the option to complete a one-time patient reported outcomes (PRO) survey.

      Results

      Among 300 patients included in the chart review, 198 (66%) received 1L PD-1/L1 inhibitor and 102 (34%) received 2L PD-1/L1 inhibitor. Following discontinuation of PD-1/L1 inhibitor therapy, 34% (n=68) received subsequent therapy in 2L and 29% (n=30) in third-line (3L). The median OS post-1L PD-1/L1 inhibitor was 9.4 (95% CI 8.6–NA) and 2.5 months (95% CI 2.24–3.50) for those who received and did not receive subsequent therapy, respectively. Following 2L PD-1/L1 inhibitor discontinuation, the median OS was 5.7 (95% CI 5.1–7.8) and 3.98 (95% CI 3.29–4.87) months for those who received and did not receive subsequent therapy, respectively. Among those with PRO data, 64% reported experiencing cancer-related pain and 29.6% received an opioid. Only 12.7% reported having a caregiver, requiring approximately 13 hours/day of service .

      Conclusions

      The symptom and caregiver burden are high among real-world patients with la/mUC who discontinued 1L or 2L PD-1/L1 inhibitors and outcomes are dismal, with a minority receiving subsequent therapy. Patterns of care in the setting of 1L maintenance avelumab and novel agents require further investigation.
      Microabstract
      Real-world patterns of care and attrition of la/mUC patients eligible for systemic therapy following PD-1/L1 inhibitors are not well understood. In an ambispective chart review of patients with la/mUC after PD-1/L1 discontinuation, only one third received subsequent treatment. Prior to the introduction of novel therapies, real-world outcomes following treatment with PD-1/L1 inhibitor therapy were poor.

      Keywords

      Abbreviations:

      1L (first-line), 2L (second-line), 3L (third-line), BPI-SF (Brief Pain Inventory—Short Form), ECOG PS (Eastern Cooperative Oncology Group performance status), EORTC (European Organisation for Research and Treatment of Cancer), EV (enfortumab vedotin-ejfv), FDA (Food and Drug Administration), FGFR (fibroblast growth factor receptor), HRQoL (health-related quality of life), IRB (institutional review board), la (locally advanced), m (metastatic), ONCS (Medical Oncologists and Hematologists/Oncologists), PD-1 (programmed death receptor-1), PD-L1 (programmed death-ligand 1), PRO (patient-reported outcome), QLQ-C30 ([Health-Related] Quality of Life Questionnaire), SD (standard deviation), SG (sacituzumab govitecan), UC (urothelial carcinoma)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Genitourinary Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bellmunt J
        • de Wit R
        • Vaughn DJ
        • et al.
        Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma.
        N Engl J Med. 2017; 376: 1015-1026
        • Powles T
        • Durán I
        • van der Heijden MS
        • et al.
        Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial.
        Lancet. 2018; 391: 748-757
      1. National Comprehensive Cancer Network. Bladder Cancer (Version 6.2021). 2021. Available at: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1417. Accessed: 21 October, 2021.

        • Rosenberg JE
        • Hoffman-Censits J
        • Powles T
        • et al.
        Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial.
        Lancet. 2016; 387: 1909-1920
        • Powles T
        • Csőszi T
        • Özgüroğlu M
        • et al.
        Pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma (KEYNOTE-361): a randomised, open-label, phase 3 trial.
        Lancet Oncol. 2021; 22: 931-945
        • Galsky MD
        • JÁA Arija
        • Bamias A
        • et al.
        Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial.
        Lancet. 2020; 395: 1547-1557
      2. US Food and Drug Administration. FDA approves avelumab for urothelial carcinoma maintenance treatment. 2020. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-avelumab-urothelial-carcinoma-maintenance-treatment#:∼:text=Efficacy%20of%20avelumab%20for%20maintenance,to%20six%20cycles%20of%20first%2D. Accessed: 14 September 2021.

        • Morgans AK
        • Grewal SK
        • Hepp Z
        • et al.
        Treatment patterns among patients with advanced urothelial carcinoma following discontinuation of PD1/L1 inhibitor therapy.
        J Clin Oncol. 2021; 39 (414–414)
        • Hepp Z
        • Shah S
        • Tan K
        • Balakrishna S.
        Real-world outcomes in patients with locally advanced or metastatic urothelial carcinoma receiving taxane monotherapy following platinum and anti-PD-1/L1 therapy.
        J Clin Oncol. 2020; 38 (458–458)
        • Hepp Z
        • Morgans A
        • Shah SN
        • et al.
        C27 Real world burden of illness and unmet need in locally advanced or metastatic urothelial carcinoma following discontinuation of PD-1/PD-L1 inhibitor therapy: a Medicare claims database analysis.
        J Manag Care Spec Pharm. 2019; 25: S34
      3. US Food and Drug Administration. FDA grants regular approval to enfortumab vedotin-ejfv for locally advanced or metastatic urothelial cancer. 2021. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-enfortumab-vedotin-ejfv-locally-advanced-or-metastatic-urothelial-cancer. Accessed: 6 September 2021.

        • Powles T
        • Rosenberg JE
        • Sonpavde GP
        • et al.
        Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma.
        N Engl J Med. 2021; 384: 1125-1135
        • Yu EY
        • Petrylak DP
        • O'Donnell PH
        • et al.
        Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV‑201): a multicentre, single-arm, phase 2 trial.
        Lancet Oncol. 2021; 22: 872-882
      4. US Food and Drug Administration. FDA grants accelerated approval to erdafitinib for metastatic urothelial carcinoma. 2019. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-erdafitinib-metastatic-urothelial-carcinoma. Accessed: 24 March 2021.

        • Loriot Y
        • Necchi A
        • Park SH
        • et al.
        Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma.
        N Engl J Med. 2019; 381: 338-348
      5. US Food and Drug Administration. FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. 2021. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sacituzumab-govitecan-advanced-urothelial-cancer. Accessed: 6 September 2021.

        • Hepp Z
        • Shah SN
        • Smoyer K
        • Vadagam P.
        Epidemiology and treatment patterns for locally advanced or metastatic urothelial carcinoma: a systematic literature review and gap analysis.
        J Manag Care Spec Pharm. 2021; 27: 240-255
        • Fayers P
        • Bottomley A.
        Quality of life research within the EORTC-the EORTC QLQ-C30. European Organisation for Research and Treatment of Cancer.
        Eur J Cancer. 2002; 38: S125-S133
        • Aaronson NK
        • Ahmedzai S
        • Bergman B
        • et al.
        The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology.
        J Natl Cancer Inst. 1993; 85: 365-376
      6. MD Anderson Cancer Center. The Brief Pain Inventory. 2021. Available at: https://www.mdanderson.org/research/departments-labs-institutes/departments-divisions/symptom-research/symptom-assessment-tools/brief-pain-inventory.html. Accessed: 8 September 2021.

        • Grewal SK
        • Hepp Z
        • Liu Y
        • et al.
        Opioid use in locally advanced or metastatic urothelial carcinoma patients and matched non-cancer controls.
        Journal of Clinical Oncology. 2021; 39 (e16517-e16517)
      7. National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Bladder Cancer. 2021. Available at: https://seer.cancer.gov/statfacts/html/urinb.html. Accessed: 9 July, 2021.

        • Cumberbatch MGK
        • Jubber I
        • Black PC
        • et al.
        Epidemiology of Bladder Cancer: A Systematic Review and Contemporary Update of Risk Factors in 2018.
        Eur Urol. 2018; 74: 784-795
        • Barata PC
        • Gopalakrishnan D
        • Koshkin VS
        • et al.
        Atezolizumab in Metastatic Urothelial Carcinoma Outside Clinical Trials: Focus on Efficacy, Safety, and Response to Subsequent Therapies.
        Target Oncol. 2018; 13: 353-361
        • Sonpavde G
        • Pond GR
        • Mullane S
        • et al.
        Outcomes in patients with advanced urothelial carcinoma after discontinuation of programmed death (PD)-1 or PD ligand 1 inhibitor therapy.
        BJU Int. 2017; 119: 579-584
        • Morgans AK
        • Rahma OE
        • Mhatre SK
        • et al.
        Treatment (tx) characteristics of patients (pts) with locally advanced or metastatic urothelial cancer (mUC) receiving checkpoint inhibitor (CPI) monotherapy in a US clinical practice.
        J Clin Oncol. 2019; 37 (4526–4526)
        • Morgans AK
        • Hepp Z
        • Shah SN
        • et al.
        Real-world burden of illness and unmet need in locally advanced or metastatic urothelial carcinoma following discontinuation of PD-1/L1 inhibitor therapy: A Medicare claims database analysis.
        Urol Oncol. 2021; 39 (733 e731–733 e710)
        • Jiang DM
        • Brundage MD
        • Sweeney C
        • et al.
        Health-Related Quality of Life (HRQOL) reporting in phase III randomized controlled trials (RCTs) of metastatic prostate adenocarcinoma (mPCa) and urothelial carcinoma (mUC).
        J Clin Oncol. 2019; 37 (478–478)
        • Taarnhoj GA
        • Lindberg H
        • Johansen C
        • Pappot H.
        Patient-Reported Outcomes, Health-Related Quality of Life, and Clinical Outcomes for Urothelial Cancer Patients Receiving Chemo- or Immunotherapy: A Real-Life Experience.
        J Clin Med. 2021; 10
        • Necchi A
        • Nishiyama H
        • Matsubara N
        • et al.
        Health-related quality of life in the randomized phase 3 study of ramucirumab plus docetaxel versus placebo plus docetaxel in platinum-refractory advanced urothelial carcinoma (RANGE).
        BMC Urol. 2020; 20: 181
        • O'Donnell PH
        • Arkenau HT
        • Sridhar SS
        • et al.
        Patient-reported outcomes and inflammatory biomarkers in patients with locally advanced/metastatic urothelial carcinoma treated with durvalumab in phase 1/2 dose-escalation study 1108.
        Cancer. 2020; 126: 432-443
      8. Group EQoL. EORTC QLQ-C30 Reference Values. 2008. Available at: https://www.eortc.org/app/uploads/sites/2/2018/02/reference_values_manual2008.pdf. Accessed: August 17, 2020.

        • Vaughn DJ
        • Bellmunt J
        • Fradet Y
        • et al.
        Health-Related Quality-of-Life Analysis From KEYNOTE-045: A Phase III Study of Pembrolizumab Versus Chemotherapy for Previously Treated Advanced Urothelial Cancer.
        J Clin Oncol. 2018; 36: 1579-1587