Oncological outcomes of intravesical gemcitabine and docetaxel for select patients with high grade recurrent NMIBC.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4546-4546 ◽  
Author(s):  
Niv Milbar ◽  
Max Kates ◽  
Meera R. Chappidi ◽  
Mark P. Schoenberg ◽  
Trinity Bivalacqua
Keyword(s):  
Disease Free Survival ◽  
Standard Of Care ◽  
Intravesical Therapy ◽  
Johns Hopkins Hospital ◽  
Bladder Preservation ◽  
Free Survival ◽  
Cox Proportional Hazard ◽  
Cox Proportional Hazard Models ◽  
Clinically Meaningful Outcomes ◽  
Muscle Invasive

4546 Background: Bacillus Calmette-Guerin (BCG) unresponsive patients with Non-Muscle Invasive Bladder Cancer (NMIBC) who prefer bladder preservation over Radical Cystectomy (RC) or are poor surgical candidates may be offered intravesical therapies. 2nd line intravesical Gemcitabine (GEM) combined with Docetaxel (DOCE) has been offered at Johns Hopkins Hospital (JHH). Our objective was to evaluate JHH experience with GEM/DOCE, and specifically to address appropriate endpoints for 2nd-line therapies in NMIBC. Methods: 33 patients who received full induction courses of GEM/DOCE since 2011, per the protocol adapted from Michael O’Donnell at U. Iowa, were identified in the IRB-approved JHH NMIBC database. Multivariable logistic regression determined factors associated with LG and HG recurrence. Cox proportional hazard models evaluated risk factors for disease free survival (DFS) and HG recurrence-free survival (HG-RFS). Results: Median DFS was 6.5 months with 42% 1-year and 24% 2-year DFS. Median HG-RFS was 17.1 months with 56% 1-year and 42% 2- year HG-RFS. Median HG-RFS among patients who initiated GEM/DOCE with HG pathology was 15.7 months, with 51% 1-year HG-RFS and 34% 2-year HG-RFS. Within initial HG-NMIBC presentation, 46% (13/28) had HG recurrence. 80% (4/5) of patients with initial LgTa had LG recurrence and 20% (1/5) had HG recurrence. There were no significant predictors for HG-RFS or DFS. There were 5 LG recurrences, and 16 HG recurrences, with 6 progressions among these. 7 patients underwent RC at a median of 14.9 months. Conclusions: GEM/DOCE is a well-tolerated alternative to immediate RC for highly selected patients with HG-NMIBC. As anticipated, including LG recurrence as an endpoint made GEM/DOCE appear less efficacious. However, since standard of care for LG recurrence is further intravesical therapy and recurrence does not result in worse cancer outcomes, it may not be an appropriate endpoint. Future studies of 2nd line therapies for NMIBC should identify endpoints based on clinically meaningful outcomes of interest.

Examining gemcitabine and docetaxel for recurrent NMIBC.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 322-322
Author(s):  
Niv Milbar ◽  
Max Kates ◽  
Meera Chappidi ◽  
Mark Schoenberg ◽  
Trinity J. Bivalacqua
Keyword(s):  
Standard Of Care ◽  
Intravesical Therapy ◽  
Johns Hopkins Hospital ◽  
Low Grade ◽  
Recurrence Free Survival ◽  
Bladder Preservation ◽  
Cox Models ◽  
Free Survival ◽  
Increased Risk ◽  
Clinically Meaningful Outcomes

322 Background: BCG relapsing/unresponsive patients who are poor surgical candidates or prefer bladder preservation vs. radical cystectomy (RC) may be offered intravesical therapies. Often in the literature, a “recurrence” after these therapies includes low-grade (LG) lesions, though stage progression and RC may be more meaningful outcomes for therapeutic efficacy. Including LG endpoints may make 2nd line therapies appear less efficacious. 2nd line intravesical Gemcitabine (GEM) with Docetaxel (DOCE) has been offered at Johns Hopkins Hospital (JHH). Our objective was to evaluate JHH experience with GEM/DOCE, and to address whether LG vs high-grade (HG) recurrence endpoints influenced outcomes. Methods: 33 patients who received full induction courses of GEM/DOCE since 2011, per the protocol adapted from Michael O’Donnell at U. Iowa, were identified in the IRB-approved JHH NMIBC database. Multivariable logistic regression determined factors associated with recurrence. Cox proportional hazard models evaluated risk factors for all-grade recurrence-free survival (AG-RFS) and HG recurrence-free survival (HG-RFS). Results: Median AG-RFS was 7.6 months with 42% 1-year and 27% 2-year AG-RFS. Median HG-RFS was 17.5 months with 57% 1-year and 44% 2-year HG-RFS. No adverse effects of GEM/DOCE were observed. There were 5 LG recurrences, 11 HG recurrences, and 3 progressions. Of these, 7 patients had RCs. Within initial LGTa presentation, 80% (4/5) had LG and 20% (1/5) had HG recurrence. Within initial HG-NMIBC presentation, 46% (13/28) had HG recurrence. Only in univariable cox models, LGTa presentation showed increased risk of AG-RFS (HR 3.18, 95% CI 1.08-9.40, p=0.036), but comparable HG-RFS (HR 0.32, 95% CI 0.04-2.47, p=0.275). Conclusions: GEM/DOCE is a well-tolerated alternative to immediate RC for highly selected patients with HG-NMIBC. As anticipated, including LG recurrence as an endpoint for RFS made GEM/DOCE appear less efficacious. However, since standard of care for LG recurrence is further intravesical therapy, this endpoint may not be appropriate, as its recurrence often does not result in RC or worse cancer outcomes. Future studies of 2nd line therapies for NMIBC should identify HG endpoints based on clinically meaningful outcomes.

The Role of Partial Cystectomy in the Treatment of Muscle-Invasive Bladder Cancer

2005 ◽  
Vol 72 (2) ◽  
pp. 215-223
Author(s):  
P. Tombolini ◽  
M. Ruoppolo ◽  
G. Dormia ◽  
E. Dormia
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Preservation ◽  
Free Survival ◽  
Muscle Invasive ◽  
Bladder Sparing ◽  
Disease Free

Partial cystectomy has been widely performed in the treatment of muscle-invasive bladder cancer in the 1960s and 70s. During the 1970s and 80s a more aggressive surgical approach was advocated by urologists. However, major complications occurred in 4–25% of patients undergoing radical cystectomy and urinary diversion. The overall survival in patients managed by radical cystectomy has increased during the last decades, but disease-free survival remains the same. This procedure allows excellent loco-regional tumor control, but not changes in the timing of distant metastases and in the failure to control the disease. Recently, multimodal strategies in sparing bladder surgery have been proposed. Neoadjuvant chemotherapy, with or without irradiation, allows bladder sparing surgery in selected patients. A literature review demonstrates a later recurrence in the preserved bladder ranging from 40–75%. One-third of these recurrences required cystectomy and 15–20% of cases with bladder preservation experienced disease progression and died of cancer within 2 yrs. Only 40 and 20% of T2-T3 bladder cancer patients are alive and disease-free at 5 and 10 yrs of follow-up, respectively. In our experience, in selected patients, disease-free survival, overall survival, time to progression and final bladder preservation rate was higher compared to other patients. Bladder sparing in selected patients, i.e. single non-recurrent neoplasm, favorable site, no prostatic or urethral involvement, complete response to neoadjuvant chemotherapy, no P53 overexpression, no previous BCG-failure, is a feasible approach. Cystectomy, possibly with neobladder tailoring, is currently, the standard therapy for muscle-invasive bladder cancer. A better understanding of bladder tumor disease is necessary to choose the optimal treatment and to control each individual patient.

scholarly journals Polymorphisms in theRANK/RANKLGenes and Their Effect on Bone Specific Prognosis in Breast Cancer Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Alexander Hein ◽  
Christian M. Bayer ◽  
Michael G. Schrauder ◽  
Lothar Häberle ◽  
Katharina Heusinger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Health ◽  
Genetic Variants ◽  
Disease Free Survival ◽  
Nucleotide Polymorphisms ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Prognostic Relevance ◽  
Cox Proportional Hazard ◽  
Cox Proportional Hazard Models

The receptor activator of NF-κB (RANK) pathway is involved in bone health as well as breast cancer (BC) pathogenesis and progression. Whereas the therapeutic implication of this pathway is established for the treatment of osteoporosis and bone metastases, the application in adjuvant BC is currently investigated. As genetic variants in this pathway have been described to influence bone health, aim of this study was the prognostic relevance of genetic variants inRANKandRANKL. Single nucleotide polymorphisms inRANK(L) (rs1054016/rs1805034/rs35211496) were genotyped and analyzed with regard to bone metastasis-free survival (BMFS), disease-free survival, and overall survival for a retrospective cohort of 1251 patients. Cox proportional hazard models were built to examine the prognostic influence in addition to commonly established prognostic factors. The SNP rs1054016 seems to influence BMFS. Patients with two minor alleles had a more favorable prognosis than patients with at least one common allele (HR 0.37 (95% CI: 0.17, 0.84)), whereas other outcome parameters remained unaffected. rs1805034 and rs35211496 had no prognostic relevance. The effect of rs1054016(RANKL) adds to the evidence that the RANK pathway plays a role in BC pathogenesis and progression with respect to BMFS, emphasizing the connection between BC and bone health.

scholarly journals 300 Final analysis of a prospective, randomized, double-blind, placebo-controlled phase IIb trial of tumor lysate, particle-loaded, dendritic cell vaccine in stage III/IV melanoma: 36-month analysis

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A327-A327
Author(s):  
Lexy Adams ◽  
Robert Chick ◽  
Guy Clifton ◽  
Timothy Vreeland ◽  
Patrick McCarthy ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Stage Iv ◽  
Standard Of Care ◽  
Stage Iii ◽  
Tumor Lysate ◽  
Double Blind ◽  
Free Survival ◽  
Resected Stage ◽  
Disease Free ◽  
Stage Iv Melanoma

BackgroundThe tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is created ex vivo by loading autologous dendritic cells (DC) with yeast cell wall particles (YCWP) containing autologous tumor lysate, thus delivering tumor antigens to the DC cytoplasm via phagocytosis. TLPLDC then activates a robust T cell response against the unique antigens for each patient. The primary analysis of the prospective, randomized, multi-center, double-blind, placebo-controlled phase IIb trial in patients with resected stage III/IV melanoma showed TLPLDC improved 24-month disease-free survival (DFS) in the per-treatment (PT) analysis (patients completing the 6-month primary vaccine series). Here, we examine the secondary endpoint of 36-month DFS and overall survival (OS).MethodsPatients with resected stage III/IV melanoma were randomized 2:1 to TLPLDC vaccine or placebo (autologous DC loaded with empty YCWP). Treatments were given at 0, 1, 2, 6, 12 and 18 months. The protocol was amended to include patients receiving concurrent checkpoint inhibitors (CPIs) to follow changes in standard of care. The co-primary endpoints were 24-month DFS by intention-to-treat (IT) analysis and per-treatment (PT) analysis, with secondary endpoints including 36-month DFS and OS by ITT and PT analysis, pre-specified analysis by stage, and safety as measured by CTCAE v4.03.ResultsOverall, 103 patients received TLPLDC and 41 placebo. In PT analysis, 65 patients received TLPLDC and 32 placebo. Total adverse events (AEs), grade 3+ AEs, and serious AEs (SAEs) were similar in placebo vs TLPLDC groups, with one related SAE per treatment arm. By ITT analysis, 36-month OS was 76.2% for TLPLDC vs 70.3% for placebo (HR 0.72, p=0.437) and 36-month DFS was 35.6% vs 27.1% (HR 0.95, p=0.841). By PT analysis, 36-month DFS was improved with TLPLDC (57.5% vs 35.0%; HR 0.50, p=0.025, figure 1). This effect was even more dramatic in resected stage IV patients (36-month DFS: 60.9% vs 0%; HR 0.12, p=0.001, figure 2).ConclusionsThis phase IIb trial again demonstrates the safety of the TLPLDC vaccine, and an improved 36-month DFS in patients with resected stage III/IV melanoma who complete the primary vaccine series, particularly in the stage IV subgroup. Next, a phase III trial will evaluate the efficacy of TLPLDC vaccine as adjuvant treatment for resected stage IV melanoma, with patients randomized to receive standard of care PD-1 inhibitors + TLPLDC versus PD-1 inhibitors + placebo.Abstract 300 Figure 136-month disease free survival for patients receiving TLPLDC vs placebo by PT analysisAbstract 300 Figure 236-month disease free survival for subset of stage IV melanoma patients receiving TLPLDC vs placebo by PT analysisTrial RegistrationThis is a phase IIb clinical trial registered under NCT02301611Ethics ApprovalThis study was approved by Western IRB, protocol 20141932.

scholarly journals Results of Early Virologic Monitoring May Facilitate Differentiated Care Monitoring Strategies for Clients on ART, Rakai, Uganda

2018 ◽  
Vol 5 (10) ◽  
Author(s):  
Victor Ssempijja ◽  
Larry W Chang ◽  
Gertrude Nakigozi ◽  
Anthony Ndyanabo ◽  
Thomas C Quinn ◽  
...  
Keyword(s):  
Predictive Value ◽  
Virologic Failure ◽  
Standard Of Care ◽  
World Health ◽  
Art Initiation ◽  
Cox Proportional Hazard ◽  
Monitoring Strategies ◽  
Cox Proportional Hazard Models ◽  
Health Organization ◽  
Differentiated Care

Abstract Background Viral load (VL) monitoring is standard of care in HIV-infected persons initiated on antiretroviral therapy (ART). We evaluated the predictive value of VL measurements at 6 and 12 months after initiation of firstline ART to estimate the future risk of virologic failure (VF). Methods HIV-infected persons with VL measurements at 6 and 12 months post-ART initiation and at least 2 additional VL measurements thereafter were assessed for risk of future VF, defined per World Health Organization guidelines. VL at 6 or 12 months post-ART was categorized into <400, 400–1000, 1001–2000, and >2000 copies/mL. Cox proportional hazard models were used to compare VF incidence associated with 6-month, 12-month, and a composite of 6- and 12-month VL prediction indicators. Results Overall, 1863 HIV-infected adults had a 6- and 12-month VL measurement, and 1588 had at least 2 additional VLs thereafter for predicting future VF. The majority (67%) were female (median age: females 33 years and males 37 years). At 12 months post-ART, 90% had VL<400 copies/mL (cumulative incidence of VF at 1.5%), 3% had 400–1000 copies/mL (VF 12%), 2% had 1001–2000 copies/mL (VF 22%), and 5% had >2000 copies/mL (VF 71%). The predictive value of the 12-month VL measurement was comparable to the composite of both the 6- and 12-month VL measurements and better than the 6-month VL measurement. Conclusions At 12 months after ART initiation, 90% of patients were virally suppressed with a low likelihood of future VF. VL measurement at 12 months post–ART initiation predicts risk of VF and could inform differentiated virologic monitoring strategies.

scholarly journals Solid component ratio influences prognosis of GGO-featured IA stage invasive lung adenocarcinoma

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Fenghao Sun ◽  
Yiwei Huang ◽  
Xiaodong Yang ◽  
Cheng Zhan ◽  
Junjie Xi ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Prognostic Value ◽  
Disease Free Survival ◽  
Ground Glass Opacity ◽  
Solid Component ◽  
Component Ratio ◽  
Tumor Diameter ◽  
Cox Proportional Hazard ◽  
Cox Proportional Hazard Models ◽  
Invasive Lung Adenocarcinoma

Abstract Background The computed tomography (CT) characteristic of ground glass opacity (GGO) were shown to be associated with clinical significance in lung adenocarcinoma. We evaluated the prognostic value of the solid component ratio of GGO IA invasive lung adenocarcinoma. Methods We retrospectively analyzed the records of GGO IA patients who received surgical resection from April 2012 to December 2015. The solid component ratio was calculated based on thin-slice CT scans. Baseline features were compared stratified by the ratio. Cox proportional hazard models and survival analyses were adopted to explore potential prognostic value regarding overall survival (OS) and disease-free survival (DFS). Results Four hundred fifteen patients were included. The higher ratio was significantly associated with larger tumor diameter, pathological subtypes and choice of surgical type. There was a significantly worse DFS with a > 50% ratio. The subgroups of 0% and ≤ 50% ratio showed close survival curves of DFS. Similar trends were observed in OS. Multivariate analyses revealed that the ratio was a significant predictor for DFS, but not for OS. No significant prognostic difference was observed between lobectomy and limited resections. Conclusion A higher solid component ratio may help to predict a significantly worse prognosis of GGO IA lung adenocarcinoma.

Phase III trial of adjuvant capecitabine/cisplatin (XP) versus capecitabine/cisplatin/RT (XPRT) in resected gastric cancer with D2 nodal dissection (ARTIST trial): Safety analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4537-4537 ◽  
Author(s):  
J. Lee ◽  
W. Kang ◽  
D. Lim ◽  
J. Park ◽  
Y. Park ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Chemoradiation Therapy ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Resected Gastric Cancer ◽  
Disease Free

4537 Background: Although the adjuvant chemoradiation therapy has gained popularity and has become the standard of care in patients with resected gastric cancer in U.S., the role of chemoradiation therapy after extended D2 dissection has been questioned. We conducted a phase III trial to compare capecitabine/cisplatin (XP) vs XP + radiotherapy (RT) in curatively D2 resected gastric cancer patients in terms of disease free survival and overall survival. Methods: Eligibility criteria were as follows: stage Ib (T1N1, T2bN0) - IV (M1 excluded), curatively ≥ D2 resected gastric adenocarcinoma. XP only: X 2,000 mg/m2/d D1∼14, CDDP 60 mg/m2 D1 repeated every 3 weeks, 6 cycles; XP + RT: X 2,000 mg/m2/d D1∼14, CDDP 60 mg/m2 D1 x 2 cycles ⋄ RT 45 Gy (25 fractions) + X 1,650 mg/m2/d during RT ⋄ X 2,000 mg/m2/d D1∼14, CDDP 60 mg/m2 D1 x 2 cycles. The primary endpoint is 3-year disease-free survival. Results: From October 2004 to April 2008, 458 patients (XP arm: 228 patients; XP/RT arm: 230 patients) were enrolled. In XP arm, 172 (75%) of 228 enrolled patients completed 6 cycles of chemotherapy. In XP + RT arm, 188 (82%) of 230 patients completed the full course of XP 2 cycles - X + RT - XP 2 cycles. Conclusions: Safety and feasibility analysis of the two arms will be reported at the meeting. No significant financial relationships to disclose.

Multi-institutional review of sequential intravesical gemcitabine and mitomycin C chemotherapy for non-muscle-invasive bladder cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 294-294
Author(s):  
Andrew J. Lightfoot ◽  
Benjamin N. Breyer ◽  
Henry M. Rosevear ◽  
Badrinath Konety ◽  
Michael A. O'Donnell
Keyword(s):  
Bladder Cancer ◽  
Mitomycin C ◽  
Median Time ◽  
Combination Chemotherapy ◽  
Invasive Bladder Cancer ◽  
Intravesical Therapy ◽  
Recurrence Free Survival ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive

294 Background: Combination chemotherapy is the standard of care for neoadjuvant, adjuvant, and metastatic bladder cancer due to increased efficacy when compared to monotherapy. We report our experience with sequential intravesical combination chemotherapy using gemcitabine and mitomycin C (MMC) for non-muscle invasive bladder cancer (NMIBC). Methods: We performed a multi-institutional retrospective review of 47 consecutive patients who received 6 weekly treatments with sequential gemcitabine (1g) and mitomycin C (40mg) chemotherapy for NMIBC. Thirty patients received treatment at University of Iowa, 14 at UCSF and 3 at University of Minnesota. Results: A total 47 patients (median age 70, range 32-85; 36 males, 11 females) previously failing a median of 2 intravesical treatments were reviewed. The complete response (CR), 1-year recurrence-free survival (1-RFS) and 2-year recurrence-free survival (2-RFS) for all patients was 68%, 48% and 38%, respectively. In all, 14 of 47 patients (30%) remain free of recurrence with a median time to followup of 26 months (range 6-80 months). The median time to recurrence for all patients who recurred was 4 months (range 1-33 months). Ten patients required cystectomy. Conclusions: Sequential intravesical combination chemotherapy using gemcitabine and MMC appears to be a useful treatment for patients with a history of NMIC which has failed BCG or other intravesical therapy, in addition to patients with intermediate and high-risk disease.

Effectiveness and safety of valrubicin in non–muscle-invasive bladder cancer following reintroduction: Results from a medical chart review study.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 296-296
Author(s):  
Michael S. Cookson ◽  
Christine Francis Lihou ◽  
Samira Q. Harper ◽  
Thomas Li ◽  
Surya Chitra ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Concomitant Medication ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
The United States ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive

296 Background: Valrubicin was approved in the United States in 1998, removed from the market in 2002 because of manufacturing issues, and reintroduced in 2009. We report secondary outcomes and concomitant medication use from a US multicenter, observational, retrospective study. Methods: Medical records of adult patients with non–muscle-invasive bladder cancer (NMIBC) who used valrubicin were abstracted (March–September 2011). Kaplan-Meier analyses were performed for disease-free survival (DFS), progression-free survival (PFS), worsening-free survival (WFS), cystectomy-free survival (CFS), and time to cystectomy. Results: 113 patients (mean age, 73.7 years) received intravesical valrubicin (median, 6 instillations [range, 2–18]). 107 patients (94.7%) received >3 instillations; 97 (85.8%) completed the full course of therapy (≥6 instillations). DFS was 51.6% (95% CI, 40.9%–61.3%) at 3 months, 30.4% (95% CI, 20.4%–41.1%) at 6 months, and median DFS was 3.5 months (95% CI, 2.5–4.0). PFS was 97.6% (95% CI, 90.9%–99.4%) at 3 months, 87.2% (95% CI, 75.4%–93.5%) at 6 months, and median PFS was 18.2 months (95% CI, 17.2–19.0). WFS was 47.4% (95% CI, 37.2%–57.0%) at 3 months and 28.1% (95% CI, 18.8%–38.2%) at 6 months. CFS was 98.0% (95% CI, 92.2%–99.5%) at 3 months and 93.7% (95% CI, 85.2%–97.4%) at 6 months. Median CFS was not reached; only 13.3% of patients underwent radical cystectomy after starting valrubicin. 56 patients (49.6%) experienced ≥1 local adverse reaction; the most common were hematuria and pollakiuria (both 17.7%), micturition urgency (15.9%), and bladder spasm (14.2%). 55 patients (48.7%) used ≥1 concomitant medication for local adverse reactions; the most commonly used were urinary antispasmodics (21.2%), fluoroquinolones (14.2%), and other urologicals (14.2%). Conclusions: In patients with NMIBC treated with intravesical valrubicin, median DFS and PFS were 3.5 and 18.2 months, respectively, and median CFS was not reached as only 13% of patients underwent radical cystectomy. Valrubicin was well tolerated, and most patients received the full course of 6 instillations. Funding: Research and abstract were supported by Endo Pharmaceuticals Inc.

Invasive urothelial cancer (iUC) with FGFR3 hotspot mutation/fusion (FGFR3+): A molecularly and clinically distinctive entity?

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 459-459
Author(s):  
Jose Mauricio S. C. Mota ◽  
Min Yuen Teo ◽  
Han Li ◽  
Arjun Vasant Balar ◽  
Matthew I. Milowsky ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Study Objective ◽  
Free Survival ◽  
Non Invasive ◽  
Genomic Landscape ◽  
Platinum Based Chemotherapy ◽  
Hotspot Mutations ◽  
Muscle Invasive

459 Background: FGFR3+ is ubiquitous in non-invasive UC but found in ~16% of iUC. We sought to characterize the genomic landscape and response to platinum-based chemotherapy (ctx) of FGFR3+ iUC in the neoadjuvant (NAC) and metastatic (mUC) setting. Methods: Two molecularly-characterized cohorts were used for the study objective: (1) NAC-treated muscle invasive UC, incorporating consecutively sequenced standard of care UC and patients (pts) from a phase II trial (Iyer et al, JCO 2018); (2) mUC treated with platinum ctx, with FGFR3- mUC from a published work (Teo et al, CCR 2017) serving as comparator. iUC with hotspot mutations / fusions were considered FGFR3+. Clinical outcomes and frequency of altered genes were compared. Results: In the NAC cohort, 87 pts were identified (NAC response: pT0 [n = 20, 23%], <pT2 [n = 22, 25%], ≥pT2 [n = 45, 52%]). FGFR3+ (n = 11, 13%) was associated with a trend towards poor NAC response and was found in 0/20 pT0 (0%), 3/22 <pT2 (14%) and 8/45 ≥pT2 (18%) (Cochran-Armitage, p=0.06). Among ≥pT2 tumors, FGFR3+ was associated with shorter recurrence-free survival (3.7 vs 17.6 months; HR 4.8 95% CI 1.9–12.1). 49 FGFR3+ mUC pts were identified and compared to FGFR3- mUC (n = 82). FGFR3+ had a numerically higher rate of lung metastasis (42% vs 29%, p = 0.25). 1st line therapies included: platinum-based ctx (n = 27), non-platinum ctx (n = 4), immunotherapy (IO, n = 13), ctx + IO (n = 4), and FGFR inhibitor (n = 1). Platinum ctx response rate for 21/27 evaluable FGFR3+ pts was 40%. FGFR3+ mUC had similar overall survival (OS, median 25.7 vs 15.8 months, HR 0.7, 95%CI 0.4-1.2; 1-year OS: 70% vs 59%) and progression-free survival (median: 7.2 vs 7.1 months, HR 1.3, 95% CI 0.8-2.1). Frequencies of altered genes are tabulated. No differences in mutational load were seen. Conclusions: FGFR3+ iUC is a genomically distinct subset of iUC. Despite low responses to NAC ctx, FGFR3+ had similar responses, PFS, and OS in the mUC setting. [Table: see text]

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