Pembrolizumab (pembro) for the treatment of patients with Bacillus Calmette-Guérin (BCG) unresponsive, high-risk (HR) non–muscle-invasive bladder cancer (NMIBC): Over two years follow-up of KEYNOTE-057.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5041-5041 ◽  
Author(s):  
Arjun Vasant Balar ◽  
Ashish M. Kamat ◽  
Girish S. Kulkarni ◽  
Edward M. Uchio ◽  
Joost L. Boormans ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Complete Response ◽  
Disease Recurrence ◽  
Intravesical Therapy ◽  
Efficacy Analysis ◽  
Bcg Therapy ◽  
Duration Of Response ◽  
Grade 3 ◽  
Muscle Invasive

5041 Background: Pembro was recently approved for the treatment of HR NMIBC based on results from the phase 2 KEYNOTE-057 (NCT02625961) study. Herein we present safety, efficacy, and posttreatment outcomes with > 2 y follow-up from KEYNOTE-057 cohort A. Methods: Patients with histologically confirmed HR BCG-unresponsive carcinoma in situ (CIS) with or without papillary tumors who received adequate BCG therapy and were ineligible for or opted out of radical cystectomy (RC) received pembro 200 mg Q3W for up to 2 y or until disease recurrence, progression, or unacceptable toxicity. The primary end point was complete response rate (CRR). Key secondary end points were duration of response (DOR) and safety. Results: Overall, 102 patients were initially enrolled, and 96 were included in the efficacy analysis. Median time from enrollment to data cut off was 28.4 months (range, 18.2-40.5). CRR was 40.6% (95% CI, 30.7-51.1), and median DOR was 16.2 months (range, 0+ to 30.4+). Among 39 patients with CR, 18 (46.2%) had a DOR ≥12 months. No patient’s disease progressed to muscle-invasive or metastatic bladder cancer while on study treatment. Median PFS and OS were not reached. At 12 months, PFS was 82.7% and OS was 97.9%. A total of 36 patients (37.5%) underwent RC after discontinuation from study treatment, which included 9 of 22 patients (40.9%) who had recurrence after initial CR and 27 of 57 (47.4%) nonresponders. Of the 36 who underwent RC, 33 (91.6%) had no pathological upstaging to MIBC and 3 (8.3%) had at least pT2 disease at time of RC. For subsequent treatments other than RC, 27 of 96 (28.1%) patients received additional intravesical therapy (eg, BCG, gemcitabine, or mitomycin), 21 of 96 (21.9%) underwent local procedures (eg, TURBT), and 3 of 96 (3.1%) received systemic therapy (eg, pembro). In 102 patients treated with pembro, treatment-related AEs (TRAEs) occurred in 67 (65.7%) patients; most frequently reported TRAEs were fatigue, pruritus, and diarrhea (10.8% each). Grade 3/4 TRAEs occurred in 13 patients (12.7%), and 21 patients (20.6%) experienced immune-mediated AEs. There were no grade 5 TRAEs. Conclusions: After > 2 y of follow-up, durable and clinically meaningful activity of pembro was observed in patients who had HR BCG-unresponsive CIS with or without papillary tumors and who were ineligible for or opted out of RC. Pembro did not seem to limit the opportunity for subsequent therapies, including RC. The safety profile was consistent with what is reported in the literature. Clinical trial information: NCT02625961 .

Keynote 057: Phase II trial of Pembrolizumab (pembro) for patients (pts) with high-risk (HR) nonmuscle invasive bladder cancer (NMIBC) unresponsive to bacillus calmette-guérin (BCG).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 350-350 ◽  
Author(s):  
Arjun Vasant Balar ◽  
Girish S. Kulkarni ◽  
Edward M. Uchio ◽  
Joost Boormans ◽  
Loic Mourey ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Complete Response ◽  
Maculopapular Rash ◽  
Median Number ◽  
Kaplan Meier ◽  
Bcg Therapy ◽  
Duration Of Response ◽  
Grade 3 ◽  
Muscle Invasive

350 Background: The PD-1 inhibitor pembro has durable antitumor activity in pts with metastatic urothelial carcinoma. Upregulation of the PD-1 pathway has been observed in BCG-resistant NMIBC, suggesting pembro may benefit. Efficacy and safety of pembro in pts with HR, BCG-unresponsive NMIBC was evaluated in the single-arm phase 2 KEYNOTE-057 study; updated results for pts with carcinoma in situ (CIS) with or without papillary tumor (cohort A) are reported. Methods: Pts with histologically confirmed HR, BCG-unresponsive CIS with or without papillary disease, who received adequate BCG therapy and were unable/unwilling to undergo radical cystectomy received pembro 200 mg Q3W for 24 mo or until recurrence, progression, or unacceptable toxicity. Pts with HR NMIBC or progressive disease during treatment were required to discontinue. Primary end point: complete response rate (CRR); key secondary end points: duration of response and safety. Results: 103 pts (median age 73 years; CIS alone 71.8%; median number of prior BCG instillations 12) have enrolled in cohort A. 3-mo CRR rate was 38.8% (95% CI 29.4%-48.9%) by central assessment. Among 40 pts who achieved CR at 3 mo, 72.5% maintained CR at last follow-up (median 14.0 mo; range 4.0-26.3) and median CR duration has not been reached (range 0+ to 14.1+ mo). 80.2% of pts had a CR duration of ≥6 mo (Kaplan-Meier method). 10 (25.0%) experienced recurrent NMIBC after CR; at the time of analysis, none progressed to muscle invasive or metastatic disease. Treatment-related adverse events (AEs) occurred in 65 (63.1%) pts; most frequent were pruritus (10.7%), fatigue (9.7%), diarrhea (8.7%), hypothyroidism (5.8%), and maculopapular rash (5.8%). Grade 3/4 treatment-related AEs occurred in 13 (12.6%) pts; 1 death was considered treatment-related (colitis in patient inadequately treated with steroids). Immune-mediated AEs occurred in 19 (18.4%) pts. Conclusions: Pembro had encouraging activity in pts with HR, BCG-unresponsive CIS with or without papillary tumors and a safety profile consistent with that of previous experience. Updated data using additional follow-up will be presented. Clinical trial. Clinical trial information: NCT02625961.

Pembrolizumab (pembro) for patients (pts) with high-risk (HR) non–muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guérin (BCG): Updated follow-up from KEYNOTE-057.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4530-4530 ◽  
Author(s):  
Ronald De Wit ◽  
Girish S. Kulkarni ◽  
Edward M. Uchio ◽  
Laurence Eliot Miles Krieger ◽  
Joost L. Boormans ◽  
...  
Keyword(s):  
Complete Response ◽  
Median Number ◽  
Kaplan Meier ◽  
Immune Mediated ◽  
Bcg Therapy ◽  
Duration Of Response ◽  
Grade 3 ◽  
Muscle Invasive

4530 Background: Upregulation of the PD-1 pathway has been observed in BCG-unresponsive NMIBC, suggesting that pembro may be beneficial. Efficacy and safety of pembro in pts with HR, BCG-unresponsive NMIBC was evaluated in the single-arm phase 2 KEYNOTE-057 study (NCT02625961); updated results for pts with carcinoma in situ (CIS) with or without papillary tumors (cohort A) are reported. Methods: Pts with histologically confirmed HR, BCG-unresponsive CIS with or without papillary tumors who received adequate BCG therapy and were unable/refused to undergo radical cystectomy received pembro 200 mg Q3W for 24 mo or until recurrence, progression, or unacceptable toxicity. Pts who developed HR NMIBC or progressive disease during treatment were required to discontinue. Key end points were complete response rate (CRR), duration of response, and safety. Results: 102 pts (median age, 73 years; CIS alone, 63.7%; median number of prior BCG instillations, 12) had enrolled in cohort A as of enrollment cutoff. Median (range) duration of follow-up was 15.8 mo (4.6-28.2) ; 3-mo CRR was 40.2% (95% CI, 30.6-50.4) by central assessment. Among 41 pts who had CR at 3 mo, median CR duration was 12.7 mo (range, 0+ to 20.5+ mo); 75.4% had a CR duration ≥ 6 mo; 52.6% had a CR duration ≥12 mo (Kaplan-Meier method); 24 pts (58.5%) maintained CR at last follow-up, and 15 (36.6%) experienced recurrent NMIBC after CR; at the time of analysis, none progressed to muscle-invasive or metastatic disease. CRR was 44.6% for pts with CIS alone (n = 65), 41.7% for CIS with T1 tumors (n = 12), and 28.0% for CIS with high-grade Ta tumors (n = 25). Treatment-related adverse events (AEs) occurred in 66 (64.7%) pts; most frequent (≥10%) were pruritus (10.8%), diarrhea (10.8%), and fatigue (9.8%). Grade 3/4 treatment-related AEs occurred in 13 (12.7%) pts. Immune-mediated AEs occurred in 19 (18.6%) pts. Conclusions: Pembro continued to show encouraging antitumor activity in pts with HR, BCG-unresponsive CIS with or without papillary tumors and a safety profile consistent with that of previous experience. Updated data using additional follow-up will be presented. Clinical trial information: NCT02625961.

Pembrolizumab for the treatment of patients with high-risk (HR) non-muscle-invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guérin: Extended follow-up of KEYNOTE-057 cohort A.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 451-451
Author(s):  
Arjun Vasant Balar ◽  
Ashish M. Kamat ◽  
Girish S. Kulkarni ◽  
Edward M. Uchio ◽  
Joost L. Boormans ◽  
...  
Keyword(s):  
Complete Response ◽  
Disease Assessment ◽  
Intravesical Therapy ◽  
Bacillus Calmette Guerin ◽  
Primary Analysis ◽  
Open Label ◽  
Efficacy Analysis ◽  
Grade 3 ◽  
Cutoff Date

451 Background: Pembrolizumab (pembro) was approved in January 2020 for treatment of HR NMIBC based on interim results from 96 patients (pts) in the open-label, single-arm, multicenter, phase II KEYNOTE-057 (NCT02625961) study. Here we present updated efficacy and safety results with extended minimum follow-up of 26.3 mo from KEYNOTE-057 cohort A. Methods: Pts aged ≥18 years with histologically confirmed Bacillus Calmette-Guérin (BCG)–unresponsive HR carcinoma in situ (CIS), with or without papillary tumors, who were ineligible for or declined radical cystectomy (RC) received pembro 200 mg Q3W for up to 24 mo or until disease persistence, recurrence, progression, or unacceptable toxicity. Primary end point: complete response rate (CRR). Key secondary end points: duration of response (DOR) and safety. Results: Overall, 101 pts received pembro and 96 were included in the efficacy analysis (5 patients did not meet BCG-unresponsive criteria). Median age was 73 years (range, 44-92), and pts received a median of 12.0 (range, 7.0-45.0) BCG instillations. Median time from enrollment to data cutoff date of May 25, 2020, was 36.4 mo (range, 26.3-48.5). Of 96 pts, CRR was 40.6% (95% CI, 30.7-51.1) at first evaluable disease assessment, and median DOR was 16.2 mo (range, 0.0+ to 36.2). Of 39 responders, 13 (33.3%) remained in CR ≥18 mo and 9 (23.1%) remained in CR ≥24 mo as of the data cutoff date. No pt progressed to MIBC while on study treatment based on protocol-specified disease assessments. CRR was generally consistent with the primary analysis across protocol-prespecified subgroups, including PD-L1 expression status. Forty pts (41.7%) underwent RC after discontinuation of pembro; 35 pts (88%) had no pathologic upstaging to MIBC, 2 (5%) had no available pathology data, and 3 (8%) had evidence of MIBC (all nonresponders); 1 pt had pT2N0 disease at 60 days after the last pembro dose, 1 pt had pT2N1 disease (involvement of a single perivesical lymph node) at 86 days after the last pembro dose, and 1 pt had pT3N1 disease at 457 days after the last pembro dose. For other subsequent treatments, 30 of 96 pts (31.3%) received additional intravesical therapy (eg, BCG), 27 of 96 (28.1%) underwent local procedures (eg, TURBT), and 10 of 96 (10.4%) received systemic therapy. In 101 pts, treatment-related AEs (TRAEs) occurred in 67 pts (66.3%); most frequent were diarrhea, fatigue, and pruritus (10.9% each). Grade 3/4 TRAEs occurred in 13 pts (12.9%). Twenty-two pts (21.8%) experienced immune-related AEs; 3.0% were grade 3-4. Seven pts (6.9%) discontinued due to TRAEs. There were no grade 5 TRAEs. Conclusions: With extended follow-up, pembro continued to show durable and clinically meaningful activity in pts who had HR BCG-unresponsive CIS with or without papillary tumors and who were ineligible for or declined RC. No new safety risks were identified. Clinical trial information: NCT02625961.

A single institution experience with induction and maintenance intravesical docetaxel in the management of non-muscle-invasive bladder cancer refractory to BCG therapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5080-5080
Author(s):  
M. C. Benson ◽  
L. Barlow ◽  
J. McKiernan
Keyword(s):  
Bladder Cancer ◽  
Maintenance Therapy ◽  
Induction Therapy ◽  
Initial Response ◽  
Invasive Bladder Cancer ◽  
Intravesical Therapy ◽  
Muscle Invasive Bladder Cancer ◽  
Entire Cohort ◽  
Muscle Invasive

5080 Background: Our initial phase I trial showed docetaxel to be a safe agent for intravesical therapy with no systemic absorption and minimal toxicity after 6 weekly instillations. In that trial, docetaxel appeared to show a 56% complete response (CR) but the durability was only 22% (no additional therapy) to 39% (CR with additional TURBT). Owing to this excellent initial response rate, a second group of patients were treated with a 6 week induction and then given monthly maintenance therapy with intravesical docetaxel for BCG refractory high-grade, non-muscle invasive bladder cancer (NMIBC). Methods: 13 patients with recurrent Ta (n=1), T1 (n=6), and Tis (n=6) TCC who failed at least one prior BCG treatment were treated. Induction therapy was administered to all 13 patients as 6 weekly instillations of 75mg intravesical docetaxel followed by single-dose monthly maintenance therapy for 9 additional instillations in 9 of the patients who experienced complete initial response. Initial response at 12 weeks from the start of induction therapy was evaluated by cystoscopy with biopsy and urine cytology. Follow-up consisted of quarterly cystoscopy with biopsy and cytology and periodic CT scans. Results: The median follow-up was 14.4 months for the entire cohort. Median duration of maintenance treatment was 9 months. 10/13 patients (77%) from the entire cohort had a complete initial response after induction, and 6/13 patients (46%) have remained disease-free in follow-up. Of those who failed, 6 patients underwent TURBT and one underwent cystectomy. 9/10 initial responders completed at least 3 doses of maintenance therapy to date, of whom 6/9 (67%) have remained recurrence-free. Conclusions: Monthly maintenance therapy with intravesical docetaxel appears to extend the durability of response to induction treatment for a select group of patients with BCG refractory high risk NMIBC and may decrease overall risk of recurrence in NMIBC. No significant financial relationships to disclose.

Nivolumab (NIVO) + low-dose ipilimumab (IPI) as first-line (1L) therapy in microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Two-year clinical update.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4040-4040 ◽  
Author(s):  
Heinz-Josef Lenz ◽  
Sara Lonardi ◽  
Vittorina Zagonel ◽  
Eric Van Cutsem ◽  
M. Luisa Limon ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Low Dose ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Duration Of Response ◽  
Therapy Option ◽  
Grade 3

4040 Background: In the phase 2 CheckMate 142 trial, NIVO + low-dose IPI had robust, durable clinical benefit and was well tolerated as 1L therapy for MSI-H/dMMR mCRC (median follow-up 13.8 months [mo; range, 9–19]; Lenz et al. Ann Oncol 2018;29:LBA18). Longer follow-up is presented here. Methods: Patients (pts) with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received NIVO 3 mg/kg Q2W + low-dose IPI 1 mg/kg Q6W until disease progression or discontinuation. The primary endpoint was investigator-assessed (INV) objective response rate (ORR) per RECIST v1.1. Results: In 45 pts with median follow-up of 29.0 mo, ORR (95% CI) increased to 69% (53–82) (Table) from 60% (44.3–74.3); complete response (CR) rate increased to 13% from 7%. The concordance rate of INV and blinded independent central review was 89%. Median duration of response (DOR) was not reached (Table). Median progression-free survival (PFS) and overall survival (OS) were not reached, and 24-mo rates were 74% and 79%, respectively (Table). Nineteen pts discontinued study treatment without subsequent therapy. An analysis of tumor response post discontinuation will be presented. Ten (22%) pts had grade 3–4 treatment-related adverse events (TRAEs); 3 (7%) had grade 3–4 TRAEs leading to discontinuation. Conclusions: NIVO + low-dose IPI continued to show robust, durable clinical benefit with a deepening of response, and was well tolerated with no new safety signals identified with longer follow-up. NIVO + low-dose IPI may represent a new 1L therapy option for pts with MSI-H/dMMR mCRC. Clinical trial information: NTC02060188 . [Table: see text]

scholarly journals Recognition and Treatment of BCG Failure in Bladder Cancer

2011 ◽  
Vol 11 ◽  
pp. 602-613 ◽  
Author(s):  
Andrew J. Lightfoot ◽  
Henry M. Rosevear ◽  
Michael A. O'Donnell
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Treatment Options ◽  
Standard Of Care ◽  
Complete Response ◽  
Bcg Therapy ◽  
Risk Patients ◽  
Bcg Failure ◽  
Muscle Invasive ◽  
American Urological Association

Patients with high-grade Ta, T1, or carcinomain situnon–muscle-invasive bladder cancer (NMIBC) are at high risk for recurrence and, more importantly, progression. Thus, both the American Urological Association and European Association of Urology recommend initial intravesical treatment with bacillus Calmette-Guerin(BCG) followed by maintenance therapy for a minimum of 1 year. The complete response rate to BCG therapy in patients with high-risk NMIBC can be as high as ∼80%; however, most patients with high-risk disease suffer from recurrence. BCG failure can be further characterized into BCG refractory, BCG resistant, BCG relapsing, and BCG intolerant. Current recommendations include one further course of BCG or cystectomy. In patients who continue to fail conservative treatment and who refuse surgical therapy or are not surgical candidates, treatment options become even more complicated. In this setting, treatment options are limited and include repeat BCG treatment, an alternate immunotherapy regimen, chemotherapy, or device-assisted therapy. To date, however, further research is necessary for all secondary treatment options in order to determine which might be the most efficacious. All conservative treatments should be considered investigational. Currently, cystectomy remains the standard of care for high-risk patients who have failed BCG therapy.

scholarly journals THE EXPERIENCE OF UK BLADDER CANCER PATIENTS DURING THE COVID-19 PANDEMIC: A SURVEY-BASED SNAPSHOT

2020 ◽  
Author(s):  
Sarah Spencer-Bowdage ◽  
Jeannie Rigby ◽  
Jackie O’Kelly ◽  
Phil Kelly ◽  
Mark Page ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Bladder Tumour ◽  
Intravesical Therapy ◽  
Cancer Services ◽  
Patient Groups ◽  
Muscle Invasive ◽  
The Uk ◽  
Second Wave ◽  
Experienced Treatment

ABSTRACTThe Covid-19 pandemic has placed unprecedented strain on healthcare systems worldwide. Within this context, UK cancer services have undergone significant disruption to create capacity for the National Health Service. As a charity that endeavours to support bladder cancer (BC) patients and improve outcomes, Action Bladder Cancer UK (ABCUK) designed and administered a SurveyMonkey survey to investigate the prevalence of such disruption for BC patients. From 22nd April to 18th June 2020, 142 BC patients responded. Across all patient groups, 46.8% of patients described disruption to their treatment or follow-up. For non-muscle-invasive BC (NMIBC) patients, disruptions included postponement of: initial transurethral resection of bladder tumour (TURBT) (33.3%), subsequent TURBT (40.0%), and surveillance cystoscopy (58.1%). For NMIBC patients undergoing intravesical therapy, 68.4% experienced treatment postponements or curtailments. For muscle-invasive BC patients, 57.1% had experienced postponement of cystectomy and 14.3% had been changed from cystectomy to radiotherapy. Half of patients undergoing systemic chemotherapy also experienced disruption. Despite the survey’s limitations, we have demonstrated considerable disruption to the care of BC patients during the UK Covid-19 pandemic. To avoid a repeat, the UK BC community should define effective contingent ways of working ready for a possible ‘second wave’ of Covid-19, or any other such threat.

scholarly journals Prospective Randomized Study between Intravesical BCG and Mitomycin-C for Non-Muscle-Invasive Urothelial Carcinoma of Urinary-Bladder Post TURBT

2016 ◽  
Vol 15 (1) ◽  
pp. 74-77 ◽  
Author(s):  
Hari Pada Mondal ◽  
Kapang Yirang ◽  
Chandranath Mukhopadhyay ◽  
Shyam Sundar Adhikary ◽  
Biswajit Dutta ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Side Effects ◽  
Urinary Bladder ◽  
Mitomycin C ◽  
Recurrence Rate ◽  
Long Term Results ◽  
Intravesical Therapy ◽  
Intravesical Bcg ◽  
Muscle Invasive

Background: Approximately 70% of urinary bladder cancer are non-muscle invasive at presentation. It is notorious for its high incidence and recurrence rate. The five-year recurrence rate varies between 30 and 60%. The intravesical treatment evolved out of need to prevent tumour recurrence after local surgical resection.Objectives: To compare intravesical Mitomycin C and BCG therapies in the prevention of recurrences and severity of their side effects.Materials and Methods: 40 patients with superficial bladder cancer were studied in urology unit of surgery department of North Bengal Medical College, Darjeeling from June, 2012 to May, 2013. They underwent transurethral resection of bladder tumour. Post operatively 19 patients were treated by intravesical Mitomycin C and 21 patients with BCG. Post intravesical therapy, patients were monitored 3 monthly for recurrence and side effects.Results: No recurrence was observed at the 3rd month follow up, two recurrences were observed at the end of 6th month in the Mitomycin C group. Regarding side effects, cystitis had no significant difference between the two groups but fever, hematuria and retention of urine were found significantly in BCG group during the study period.Conclusions: In the prevention of recurrences, intravesical Mitomycin C and BCG therapies have comparable efficacies at the end of 6 months. A further follow up period is required to see and compare the long term results. The incidence of the side effects although mild was much higher with intravesical BCG therapy.Bangladesh Journal of Medical Science Vol.15(1) 2016 p.74-77

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