A Study of RC48-ADC in Subjects With HER2-negative Locally Advanced or Metastatic Urothelial Cancer

Author(s):  
2017 ◽  
Vol 18 (2) ◽  
pp. 212-220 ◽  
Author(s):  
Elizabeth R Plimack ◽  
Joaquim Bellmunt ◽  
Shilpa Gupta ◽  
Raanan Berger ◽  
Laura Q M Chow ◽  
...  

Author(s):  
M. Sotelo ◽  
T. Alonso-Gordoa ◽  
P. Gajate ◽  
E. Gallardo ◽  
R. Morales-Barrera ◽  
...  

Abstract Background The studies IMvigor 210 cohort 2 and IMvigor211 evaluated the efficacy of atezolizumab in patients with locally advanced or metastatic urothelial cancer (mUC) upon progression to platinum-based chemotherapy worldwide. Yet, the real impact of this drug in specific geographical regions is unknown. Materials and methods We combined individual-level data from the 131 patients recruited in Spain from IMvigor210 cohort 2 and IMvigor211 in a pooled analysis. Efficacy and safety outcomes were assessed in the overall study population and according to PD-L1 expression on tumour-infiltrating immune cells. Results Full data were available for 127 patients; 74 (58%) received atezolizumab and 53 (42%) chemotherapy. Atezolizumab patients had a numerically superior median overall survival although not reaching statistical significance (9.2 months vs 7.7 months). No statistically significant differences between arms were observed in overall response rates (20.3% vs 37.0%) or progression-free survival (2.1 months vs 5.3 months). Nonetheless, median duration of response was superior for the immunotherapy arm (non-reached vs 6.4 months; p = 0.005). Additionally, among the responders, the 12-month survival rates seemed to favour atezolizumab (66.7% vs 19.9%). When efficacy was analyzed based on PD-L1 expression status, no significant differences were found. Treatment-related adverse events of any grade occurred more frequently in the chemotherapy arm [46/57 (81%) vs 44/74 (59%)]. Conclusion Patients who achieved an objective response on atezolizumab presented a longer median duration of response and numerically superior 12 month survival rates when compared with chemotherapy responders along with a more favorable safety profile. PD-L1 expression did not discriminate patients who might benefit from atezolizumab.


2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 4547-4547
Author(s):  
Patrizia Giannatempo ◽  
Biagio Paolini ◽  
Salvatore Lo Vullo ◽  
Manuela Marongiu ◽  
Elena Farè ◽  
...  

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4556-4556
Author(s):  
Gwynn Ison ◽  
Virginia Ellen Maher ◽  
Chana Weinstock ◽  
Sundeep Agrawal ◽  
Michael Holman Brave ◽  
...  

4556 Background: Registrational trials of PD-1/PD-L1 inhibitor therapy help inform clinicians and patients about the expected outcomes of patients receiving these drugs. However, the clinical trial population does not reflect all patients with the underlying disease. There have been ongoing efforts to expand eligibility criteria for clinical trial enrollment that are expected to mitigate some of these factors. We reviewed four registrational trials of PD-1/PD-L1 inhibitor therapy to better understand why patients were deemed ineligible for trial enrollment and whether expanded eligibility criteria may have addressed the reasons for ineligibility. Methods: We reviewed four trials that led to approval of PD-1/PD-L1 inhibitor therapy. These trials screened 1931 and enrolled 1253 patients with metastatic or locally advanced urothelial cancer who had previously received platinum-based therapy. We examined the datasets to determine patient demographics and reasons for trial ineligibility. Results: There were no differences in the demographics characteristics of patients who were eligible or ineligible for study treatment. However, when compared to the SEER database the screened population was younger, and minorities were under-represented. Causes of patient ineligibility included: 1) Lack of Tumor Tissue/PD-L1 Low Tumor Staining (23%), 2) Underlying Disease characteristics were not met (19%), 3) Laboratory Abnormalities (18%), 4) Excluded Co-morbid Conditions (16%), 5) Poor Performance Status (15%), 6) Refused Consent (10%), 7) Other (7%), and 8) Incorrect Prior Therapy (5%). Conclusions: Clinical trial accrual should be representative of all patients with the underlying disease. Changes in trial eligibility criteria such as less stringent requirements concerning tumor tissue (when possible), co-morbid conditions, laboratory abnormalities, and performance status may improve patient accrual. These, when added together, formed the majority of the reasons for clinical trial ineligibility.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4526-4526
Author(s):  
Alicia K. Morgans ◽  
Osama E. Rahma ◽  
Shivani K. Mhatre ◽  
Ching-Yi Chuo ◽  
Jessica Davies ◽  
...  

4526 Background: Approval of anti–PD-L1/anti–PD-1 CPI agents has changed the mUC tx landscape, but real-world (RW) tx patterns are not well described. Here, we describe pt characteristics, time on tx (TOT), tx-cycle distribution, relative dose intensity (RDI) and subsequent tx for pts receiving atezolizumab (atezo), nivolumab (nivo) or pembrolizumab (pembro) monotherapy. Methods: Pts diagnosed with mUC who completed atezo, nivo or pembro in the first-line (1L) or prior-platinum second-line and beyond (2L+) settings by April 30, 2018, were identified from the US-based Flatiron Health electronic health record–derived database. TOT was defined as time from first to last CPI administration + 1 cycle, tx cycles as number of CPI doses received during TOT and RDI as ratio of actual to planned dose per week to reflect any dose interruption. Results: RW data from pts receiving atezo, nivo and pembro were analyzed (Table). Up to 38% of pts had ECOG PS > 1. Median TOT ranged from 2.1-2.8 mo, with overlapping 95% CIs; mean TOT ranged from 2.7-4.1 mo. Over 50% of pts had ≤ 4 tx cycles. 21%-38% of pts did not have RDI within 95%-105% of the labeled dose. Most common subsequent txs were platinum-based chemotherapy combinations with gemcitabine or taxanes (post–1L CPI) and taxane monotherapy or other CPI monotherapy/combinations (post–2L+ CPI). Conclusions: Here, we present the largest analysis of RW CPI use in mUC to date. Overall, this unadjusted descriptive analysis showed relative comparability of pt and tx characteristics and TOT across CPI-treated groups. Insights into RW tx allow for an understanding of how clinical trial data translate to broader pt populations, including those with ECOG PS > 1, and may be useful for practitioners. [Table: see text]


2020 ◽  
Vol 23 ◽  
pp. S480
Author(s):  
S.N. Shah ◽  
Z. Hepp ◽  
S. Martin ◽  
N. Harris ◽  
A. Morgans

2004 ◽  
Vol 22 (5) ◽  
pp. 393-397 ◽  
Author(s):  
Donald S. Kaufman ◽  
Michael A. Carducci ◽  
Tim M. Kuzel ◽  
Mary B. Todd ◽  
William K. Oh ◽  
...  

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