Abstract 3246
Background
Erda, a pan-fibroblast growth factor receptor (FGFR) inhibitor recently received accelerated US FDA approval for locally advanced or metastatic urothelial cancer (mUC) in adult patients (pts) with FGFR2/3 alterations who progressed on ≥ 1 prior platinum-containing chemotherapy, based on a single-arm phase 2 study. In the absence of head-to-head studies, a matching-adjusted indirect comparison (MAIC) was used to compare the efficacy of erda relative to available therapies in mUC pts.
Methods
Systematic literature review was performed to identify published randomized controlled trials (RCTs) of 2nd-line treatments (from 1990-on) in mUC pts with unknown FGFR status. Individual patient-level data (IPD) were used from the phase 2 study (NCT02365597) in mUC pts treated with erda (8 mg/day). ORR (primary endpoint), overall survival (OS) and progression-free survival (PFS) were compared using an unanchored MAIC. The IPD were weighted to match the aggregated data from comparator studies.
Results
Nine relevant RCTs of 6 comparators (docetaxel [D], vinflunine [V], pembrolizumab [Pb], atezolizumab [A], paclitaxel [P], and mixed-chemotherapy [D, V or P]) that were identified could be matched with. The matching-adjusted odds ratios (OR) for ORR were consistently >1 vs all comparators, suggesting higher ORR with erda treatment over all comparator 2nd-line therapies. The matching-adjusted hazard ratios (HRs) for OS and PFS vs all comparators were <1, suggesting better outcomes (PFS/OS) with erda. Results from the sensitivity analyses showed varied statistical significance, however, the overall trends were relatively similar. Study limitations: availability of comparable endpoints and baseline characteristics; small sample size of the erda study.Table:
926P MAIC results for base case scenario: Erda (in FGFR+ pts) vs available 2nd-line therapies in pts with unknown FGFR status
| Comparator | Study | N (Neff) | ORR (OR [95% CI]) | OS (HR [95% CI]) | PFS (HR [95% CI]) |
|---|---|---|---|---|---|
| Pembrolizumab | NCT02256436 | 79 (40) | 2.26 [1.11; 4.59]* | 0.61 [0.37; 0.99]* | 0.77 [0.58; 1.03] |
| Atezolizumab | NCT02302807 | 74 (45) | 6.80 [3.55; 13.02]*** | 0.58 [0.37; 0.92]* | |
| Mixed-chemotherapy | NCT02256436 | 79 (45) | 4.15 [2.04; 8.46]*** | 0.54 [0.35; 0.85]** | 0.77 [0.56; 1.07] |
| Mixed-chemotherapy | NCT02302807 | 74 (51) | 6.26 [3.37; 11.63]*** | 0.54 [0.34; 0.84]** | |
| Docetaxela | NCT01282463 | 68 (45) | 3.71 [1.11; 12.35]* | 0.72 [0.41; 1.25] | 0.51 [0.32; 0.80]* |
| Docetaxel | NCT00880334 | 78 (42) | 3.98 [1.48; 10.74]** | 0.52 [0.31; 0.87]* | 0.84 [0.56; 1.26] |
| Docetaxel | NCT01780545 | 84 (47) | 6.02 [2.48; 14.63]*** | 0.37 [0.23; 0.61]*** | |
| Docetaxel | NCT02426125 | 78 (63) | 3.46 [1.80; 6.66]** | 0.63 [0.47; 0.84]* | |
| Vinfluninea | NCT00315237 | 78 (53) | 4.74 [2.21; 10.18]*** | 0.57 [0.39; 0.84]** | |
| Vinflunine | NCT01830231 | 61 (32) | 1.51 [0.45; 5.10] | 0.49 [0.24; 0.99]* | 0.96 [0.51; 1.81] |
| Paclitaxela | NCT00949455 | 68 (44) | 2.63 [1.03; 6.73]* | 0.59 [0.37; 0.95]* | 0.95 [0.64; 1.41] |
p ≤ 0.05;
**p ≤ 0.01;
***p ≤ 0.0001
For most comparators, only the main characteristics (according to clinical experts; number of risk factors, ECOG, liver metastases, hemoglobin<10g/dl, visceral disease, liver/bone metastasis, metastatic disease, primary tumor site, smoking status, and time since prior therapy) were included in the base case matching process to maintain a reasonable effective sample size (Neff). aAll available characteristics were included. When type of ORR (assessment by independent review committees [IRR] or assessment by investigators) is not specified for the comparator study, IRR was used for erda as this leads to conservative results.
Conclusions
Treatment of FGFR+ mUC pts with erda may be associated with improved overall response, PFS and OS as compared to available therapies in pts with unknown FGFR status.
Clinical trial identification
NCT02365597.
Editorial acknowledgement
Priya Ganpathy, MPharm, ISMPP CMPP™ (SIRO Clinpharm Pvt. Ltd, India) provided writing assistance and Harry Ma, PhD (Janssen Global Services) provided additional editorial support.
Legal entity responsible for the study
Janssen Research & Development, LLC.
Funding
Janssen Research & Development, LLC.
Disclosure
Y. Loriot: Honoraria (self), Consultancy / Advisory Role- Astellas Pharma, AstraZeneca, Janssen, Merck Sharp & Dohme, Pfizer, Roche, Ipsen, Seattle Genetics, Sanofi; Research Funding- Sanofi (Inst) S. Van Sanden: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. J. Diels: Shareholder / Stockholder / Stock options, Employee and Share holder: Janssen Reserach & Development. N. Rahhali: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. D. Seshagiri: Shareholder / Stockholder / Stock options, Employee & stockholder: Janssen Reserach & Development. B. Kowalski: Shareholder / Stockholder / Stock options, Employee & stockholder: Janssen Research & Development. S. Fleming: Shareholder / Stockholder / Stock options, Employee & stockholder: Janssen Research & Development. P. De Porre: Shareholder / Stockholder / Stock options, Employee & stockholder: Janssen Research & Development. A.O. Siefker-Radtke: Consulting / Advisory Role: AstraZeneca, Bristol-Myers Squibb, Eisai, EMD Serono, Genentech, Inovio Pharmaceuticals, Janssen, Lilly, Merck, NCCN; Speakers’ Bureau: Genentech; Research funding: Bristol-Myers Squibb, Janssen, Michael, Sherry Sutton; Fund for Urothelial Cancer: NIH, Takeda; Patents / Royalties / Other Intellectual Property: Methods of characterizing and treating molecular subsets of muscle-invasive bladder cancer.
Resources from the same session
3186 - The landscape of immuno-oncology clinical trials in China
Presenter: Dawei Wu
Session: Poster Display session 3
Resources:
Abstract
3468 - Clinical Significance of Immune-related Creatine Phosphokinase Increase Associated with Anti PD1/PD-L1 immunotherapies.
Presenter: Samia Hajem
Session: Poster Display session 3
Resources:
Abstract
3836 - Thyroid toxicity and anti-thyroid antibodies as predictive markers for patients treated with anti-PD1 checkpoint therapy
Presenter: Wim Meer
Session: Poster Display session 3
Resources:
Abstract
1343 - Treatment-related adverse events and tolerability in patients with advanced renal cell carcinoma treated with first-line combination therapy with checkpoint inhibitors
Presenter: Thura Win Htut
Session: Poster Display session 3
Resources:
Abstract
5783 - Immune-related adverse events (irAEs) with single-agent PD-1 vs PD-L1 inhibitors: a meta-analysis of 8,730 patients from clinical trials
Presenter: Guru Sonpavde
Session: Poster Display session 3
Resources:
Abstract
5422 - EULAR recommendations for the diagnosis and the management of rheumatic immune-related adverse events due to cancer immunotherapy
Presenter: Marie Kostine
Session: Poster Display session 3
Resources:
Abstract
1202 - Radiographic characteristics and poor prognostic factors of interstitial lung disease (ILD) in nivolumab-treated patients with non-small cell lung cancer (NSCLC)
Presenter: Shinichi Sasaki
Session: Poster Display session 3
Resources:
Abstract
2749 - Use of Checkpoint Inhibitors (CPI) in Allogeneic Stem Cell Transplant Recipients: An Institutional Experience and A Systemic Review of the Literature
Presenter: Chantal Saberian
Session: Poster Display session 3
Resources:
Abstract
3256 - Deep Learning Radiomics distinguishes intrapulmonary Disease from Metastases in Immunotherapy-treated Melanoma Patients
Presenter: Thi Dan Linh Nguyen-Kim
Session: Poster Display session 3
Resources:
Abstract
5031 - Sarcoidosis-Like Reaction Mimics Progression in patients treated with immune checkpoint inhibitors
Presenter: Sophie Hans
Session: Poster Display session 3
Resources:
Abstract