scholarly journals 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

2021 ◽  
Author(s):  
Alicia K. Morgans ◽  
Zsolt Hepp ◽  
Sonali N. Shah ◽  
Anne Shah ◽  
Allison Petrilla ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Real World ◽  
Burden Of Illness ◽  
Locally Advanced ◽  
Unmet Need ◽  
Inhibitor Therapy ◽  
Database Analysis ◽  
Claims Database ◽  
Medicare Claims ◽  
Metastatic Urothelial Carcinoma

Treatment patterns among patients with advanced urothelial carcinoma following discontinuation of PD1/L1 inhibitor therapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 414-414
Author(s):  
Alicia K. Morgans ◽  
Simrun Kaur Grewal ◽  
Zsolt Hepp ◽  
Rupali Fuldeore ◽  
Shardul Odak ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Real World ◽  
Chart Review ◽  
Group Performance ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Unmet Need ◽  
Case Series ◽  
Treatment Patterns

414 Background: There are a lack of published real-world data on treatment patterns for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) previously treated with programmed death 1/ligand 1 inhibitor (PD-1/L1i) therapy. The objective of this study was to characterize the clinical characteristics and treatments among patients with la/mUC following discontinuation of first-line (1L) or second-line (2L) PD-1/L1i therapy. Methods: We performed a retrospective chart review at 26 geographically diverse clinical sites in the US. Patients aged ≥18 years with histologically or cytologically confirmed urothelial carcinoma and radiographic evidence of metastatic or locally advanced disease were identified. Included patients had initiated and subsequently discontinued PD-1/L1i therapy in the 1L or 2L setting for la/mUC between May 15, 2016-July 31, 2018. All patients had follow-up through October 31, 2019. Data were summarized using descriptive statistics. Results: Among the 300 patients included in the chart review, 198 (66%) received PD-1/L1i therapy as 1L and 102 (34%) as 2L therapy. Mean (SD) age at la/mUC diagnosis was 69.4 (8.7) years, and a majority of patients were male (66.0%) and White (74.7%). Consistent with age, most patients (82.7%) had comorbidities at la/mUC diagnosis; 39.7% hypertension, 23.7% coronary artery disease, 17.7% pulmonary disease, and 9.3% renal disease. At initiation of therapy, a higher proportion of patients who received 1L PD-1/L1i therapy had an Eastern Cooperative Oncology Group performance status of 2 or more than patients who received 2L PD-1/L1i therapy (36.8% vs 22.5%, respectively). Following discontinuation of PD-1/L1i therapy, 34% (n = 68) received subsequent therapy in 2L and 29% (n = 30) in third-line (3L). The most common subsequent therapies in 2L were gemcitabine monotherapy (24%), gemcitabine plus cisplatin or carboplatin (22%), PD-1/L1i therapy (22%), and taxane monotherapy (19%). The most common subsequent therapies received in 3L were taxane monotherapy (50%), pemetrexed (17%), and PD-1/L1i therapy (16%). Overall, switching from one PD-1/L1i therapy to another distinct PD-1/L1i therapy occurred in approximately 20% of patients, with “better efficacy/survival” noted by treatment teams as the most common reason for switching therapy among this subgroup. Conclusions: In this real-world case series, only a minority of patients with la/mUC who discontinued PD-1/L1i therapy received subsequent therapy. Among those that did, no clear standard of care was observed and approximately one-fifth of patients were treated with a second PD-1/L1i therapy after the first failed to control disease. Collectively, the data highlight significant unmet need for patients with la/mUC who discontinue PD-1/L1i therapy.

Real-world outcomes in patients with locally advanced or metastatic urothelial carcinoma receiving taxane monotherapy following platinum and anti-PD-1/L1 therapy.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 458-458
Author(s):  
Zsolt Hepp ◽  
Sonali Shah ◽  
Katherine Tan ◽  
Shreya Balakrishna
Keyword(s):  
Urothelial Carcinoma ◽  
Clinical Outcomes ◽  
Real World ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Disease Status ◽  
Study Cohort ◽  
Start Date ◽  
Metastatic Urothelial Carcinoma ◽  
Platinum Chemotherapy

458 Background: There are currently limited options for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) following progression on platinum chemotherapy and anti-programmed death 1/death-ligand 1 (PD-1/L1) therapy. Further, limited data are available from clinical trials or real-world studies on outcomes in this population. This retrospective analysis investigated clinical outcomes in patients treated with taxane monotherapy, a commonly used and NCCN guideline-recommended option in this setting. Methods: Patients aged ≥18 years with histologically-confirmed diagnosis of la/mUC on or after 2011, ≥2 clinical visits, and sufficient relevant unstructured data were included from the de-identified nationwide Flatiron Health electronic health record-derived database. The study cohort included patients treated with taxane monotherapy (docetaxel, paclitaxel, or nab-paclitaxel) following anti-PD-1/L1 therapy and who have received prior platinum containing chemotherapy. Baseline characteristics, overall survival (OS), real-world progression-free survival (rwPFS) based on clinician documentation of disease status, and real-world response (rwR) based on clinician-confirmed radiologic assessments were reported. Patients were followed until death, data cutoff, or loss to follow up. Results: Among 276 patients treated following anti-PD-1/L1 therapy and who met all of the inclusion/exclusion criteria, 72 were treated with taxanes and also had documented prior platinum chemotherapy. Patients were mostly male (75%) and Caucasian (74%), with a mean age of 73 years. 65% had > 2 sites of metastasis at index (start date of taxane). Post index, median OS = 7.6 months (95% CI 5.2, 14.4) and median rwPFS = 2.9 months (95% CI, 2.4, 4.0). Among the 50 patients with ≥1 rwR assessment, confirmed rwR = 18% (95% CI: 9%, 32%). Conclusions: In the real-world setting, limited responses to taxanes and short duration of PFS and OS were observed in patients with la/mUC previously treated with a platinum and anti-PD-1/L1 therapy. There is a need for more effective therapies to improve clinical outcomes for this patient population.

Study EV-103: Update on durability results and long term outcome of enfortumab vedotin + pembrolizumab in first line locally advanced or metastatic urothelial carcinoma (la/mUC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4528-4528
Author(s):  
Terence W. Friedlander ◽  
Matthew I. Milowsky ◽  
Mehmet Asim Bilen ◽  
Sandy Srinivas ◽  
Rana R. McKay ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Objective Response ◽  
Locally Advanced ◽  
Unmet Need ◽  
First Line ◽  
Antibody Drug Conjugate ◽  
Durable Response ◽  
Long Term Outcome ◽  
Metastatic Urothelial Carcinoma

4528 Background: Significant unmet need remains for people with cisplatin-ineligible (cis-ineligible) locally advanced or metastatic urothelial carcinoma (la/mUC). In the first-line (1L) setting, carboplatin-based regimens have demonstrated poor tolerability, modest objective response rate (ORR) and limited durability. PD-1/PD-L1 inhibitors demonstrate durable responses; however, only a minority of pts achieve a response (ORR 24-29%). Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) delivering the microtubule-disrupting agent monomethyl auristatin E (MMAE) to targeted tumor cells expressing Nectin-4. EV has shown an overall survival benefit versus chemotherapy in previously treated la/mUC. Preclinical studies show that ADCs utilizing MMAE can induce immunogenic cell death and may enhance antitumor immunity. Clinical data suggests the combination of EV + pembrolizumab (P) may have the potential to induce greater antitumor activity compared to either agent alone. Preliminary data on EV + P was previously presented, and the FDA granted breakthrough therapy designation to EV + P for the treatment of pts with 1L cis-ineligible la/mUC in Feb 2020. Here we report updated data with 24.9 months median follow-up. Methods: This multi-cohort EV-103 study (NCT03288545) evaluates the safety/activity of EV + P (Dose Escalation/Cohort A). This report highlights 1L cis-ineligible pts treated with 3-week cycles of EV 1.25 mg/kg (Days 1, 8) and P (Day 1). Endpoints include safety/tolerability, investigator response per RECIST v1.1, DOR, PFS, and OS. Results: As of 13 Oct 2020, the median follow-up for the 45 1L la/mUC pts (median age 69 yrs [51-90]) was 24.9 months. The median number cycles of EV + P was 9 (range 1-34). The most common treatment-related adverse events were peripheral sensory neuropathy (56%, 4% ≥G3), fatigue (51%, 11% ≥G3), and alopecia (49%). There was one death reported as possibly related to study treatment (multiple organ dysfunction syndrome) per investigator assessment. Confirmed ORR is 73.3% (95% CI: 58.1, 85.4) including 17.8% CR and an ORR of 57.1% (8/14) in pts with liver metastasis. The median DOR was 25.6 months (95% CI: 8.3, -). Fifty-three percent of the responders had DOR at 24 months. Additionally, the DCR is 93.3%, the median PFS is 12.3 months (95% CI: 8.0, -), and the median OS is not reached. The OS rate at 24 months is 56.3% (95% CI: 39.8, 69.9). Conclusions: EV + P, a platinum-free option, continues to demonstrate promising activity with a durable response profile in 1L cis-ineligible pts with la/mUC. The safety profile is manageable and stable over time with no new safety signals. Cohort K of EV-103 in cis-ineligible pts with la/mUC is actively randomizing pts to EV monotherapy or EV + P to evaluate the contribution of each agent. Clinical trial information: NCT03288545.

scholarly journals Real-world outcomes in locally advanced or metastatic urothelial carcinoma following platinum and PD-1/L1 inhibitor therapy

2021 ◽  
Author(s):  
Zsolt Hepp ◽  
Sonali N Shah ◽  
Shang-Ying Liang ◽  
Katherine Tan ◽  
Shreya Balakrishna
Keyword(s):  
Overall Survival ◽  
Urothelial Carcinoma ◽  
Real World ◽  
Patient Population ◽  
Locally Advanced ◽  
Death Receptor ◽  
Progression Free Survival ◽  
Health Record ◽  
Free Survival ◽  
Metastatic Urothelial Carcinoma

Aim: To investigate real-world overall survival (rwOS) and real-world progression-free survival (rwPFS) in locally advanced/metastatic urothelial carcinoma postplatinum and postprogrammed death receptor-1/death ligand 1 inhibitors. Patients & methods: Adult patients diagnosed with locally advanced/metastatic urothelial carcinoma from 1 January 2011 to 31 December 2018 and treated with taxane monotherapy or any therapy postplatinum and post-PD-1/L1 inhibitors were included from a nationwide electronic health record-derived oncology database. Results: Median rwOS among 72 patients treated with taxane monotherapy was 7.6 months (95% CI: 5.2–14.4) and rwPFS was 2.9 months (95% CI: 2.4–4.0). Among 208 patients treated with any therapy, median rwOS was 8.9 months (95% CI: 7.3–10.6) and rwPFS was 3.6 months (95% CI: 2.7–4.7). Conclusion: Short duration of rwOS and rwPFS were observed, highlighting the need for effective and safe treatments in this patient population.

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