Dr. Guru Sonpavde, Bladder Cancer Director at the Dana-Farber Cancer Institute and Editor-in-Chief of the PracticeUpdate Center of Excellence for Bladder Cancer, recommends the following abstracts being presented at this year's ASCO Annual Meeting, held June 3 through June 7, 2022, in Chicago and simultaneously online.
Oral Abstract Session: Genitourinary Cancer—Kidney and Bladder
Friday, June 3, 2022; 3:45 PM–6:45 PM EDT
4504 SK Pal, N Agarwal, P Singh, et al
Take-Home Message
- Cabozantinib, a multitargeted receptor TKI, and atezolizumab, an anti–PD-LI agent, had promising clinical activity in patients with inoperable locally advanced or metastatic urothelial carcinoma. The combination was studied as first-line systemic therapy in patients eligible or ineligible for cisplatin-based chemotherapy who had no prior therapy and as second-line or later in patients who had received one prior ICI and no prior VEGFR-TKI.
- Toxicity was manageable.
A randomised, double blind, phase II clinical trial of maintenance cabozantinib following chemotherapy for metastatic urothelial carcinoma (mUC): Final analysis of the ATLANTIS cabozantinib comparison.
RJ Jones, SA Hussain, AJ Birtle, et al
4506 Cell-free DNA methylation as a predictive biomarker of response to neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer in SWOG S1314. YT Lu, M Plets, G Morrison, et al
Take-Home Message
- The researchers involved in this prospective study used plasma cfDNA to develop a response score based on cfDNA methylation to predict which patients with muscle-invasive bladder cancer would benefit most from neoadjuvant chemotherapy. Blood samples were collected before and after one cycle of neoadjuvant therapy, and the methylation signatures were correlated with pathologic response.
- The pathologic response was successfully predicted in 79% of the 73 patients enrolled, providing proof of concept that cfDNA methylation may be used to predict response to neoadjuvant chemotherapy in patients with bladder cancer.
4507 TRUCE-02: An open label, single-arm, phase II study of tislelizumab combined with nab-paclitaxel for high-risk non-muscle-invasive urothelial bladder carcinoma. HT Wang, H Hu, Y Niu, et al
4508 Final clinical results of pivotal trial of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive CIS and papillary nonmuscle-invasive bladder cancer (NMIBC). K Chamie, SS Chang, M Gonzalgo, et al
Take-Home Message
- This multicenter study of patients with high-grade non–muscle-invasive bladder cancer unresponsive to BCG looked at the efficacy and safety of intravesical BCG plus Anktiva (N-803). Among the 160 participants enrolled, 77 have papillary disease and 83 have carcinoma in situ. At 2 years, 90% of participants have avoided cystectomy, and overall bladder cancer–specific survival is 99%. At a median of 24.1 months’ duration of response, the complete response rate is 71% in patients with carcinoma in situ. The disease-free survival rate is 53% at 18 months in patients with papillary disease.
- The combination of Anktiva and BCG exceeds other intravesical and systemic treatment options in terms of safety and efficacy for patients with non–muscle-invasive bladder cancer.
Poster Session: Genitourinary Cancer—Kidney and Bladder
Saturday, June 4 2022; Starting at 2:15 PM EDT
4521 Association of DNA damage repair (DDR) mutations (mts) and clinical outcomes in CALGB 90601 (Alliance). G Iyer, et al
4522 Association of DNA damage response (DDR) gene mutations (mts) and response to neoadjuvant cisplatin-based chemotherapy (chemo) in muscle-invasive bladder cancer (MIBC) patients (pts) enrolled onto SWOG S1314. G Iyer, et al
4559 Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): Long-term outcomes from JAVELIN Bladder 100 in subgroups defined by response to 1L chemotherapy. B Pérez-Valderrama, et al
Poster Discussion Session: Genitourinary Cancer—Kidney and Bladder
Saturday, June 4, 2022; 5:30 PM–7:00 PM EDT
4516 Long-term outcomes in EV-301: 24-month findings from the phase 3 trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma. JE Rosenberg, T Powles, GP Sonpavde, et al
Take-Home Message
- The 24-month findings of a phase III trial of the antibody–drug conjugate enfortumab vedotin (EV) in patients with previously treated locally advanced or metastatic urothelial carcinoma (la/mUC) confirm the survival advantage versus standard chemotherapy evident in the 12-month interim analysis. At 24 months, the median overall survival was 12.91 months with EV compared with 8.94 months with chemotherapy, a significant 3.97-month advantage. EV also was associated with a longer progression-free survival of a median 5.55 months compared with the chemotherapy median of 3.71 months.
- Patients with previously treated la/mUC experience a significant benefit in survival compared with those treated with standard chemotherapy, with no new safety signals.
Avelumab as the basis of neoadjuvant regimen in platinum-eligible and -ineligible patients with nonmetastatic muscle-invasive bladder cancer: AURA (Oncodistinct-004) trial. N Martinez Chanza, A Carnot, P Barthélémy, et al
Preliminary results of a phase Ib/II combination study of RC48-ADC, a novel humanized anti-HER2 antibody-drug conjugate (ADC) with toripalimab, a humanized IgG4 mAb against programmed death-1 (PD-1) in patients with locally advanced or metastatic urothelial carcinoma. X Sheng, L Zhou, Z He, et al
4519 A phase II study of RC48-ADC in HER2-negative patients with locally advanced or metastatic urothelial carcinoma. H Xu, X Sheng, L Zhou, et al
4520 RC48-ADC for metastatic urothelial carcinoma with HER2-positive: Combined analysis of RC48-C005 and RC48-C009 trials. X Sheng, Z He, Y Shi, et al
Dr. Petros Grivas, an Associate Professor and Clinical Director of Genitourinary Cancers Program at the University of Washington, and a member of the Advisory Board for PracticeUpdate Center of Excellence for Bladder Cancer, recommends the following abstracts that will be presented at this year's ASCO Annual Meeting, held June 3 through June 7, 2022, in Chicago and simultaneously online.
Oral Abstract Session: Genitourinary Cancer—Kidney and Bladder
Friday, June 3, 2022; 3:45 PM–6:45 PM EDT
LBA4500 EVEREST: Everolimus for renal cancer ensuing surgical therapy—A phase III study (SWOG S0931, NCT01120249). CW Ryan, C Tangen, EI Heath, et al
LBA4503 CALYPSO: A three-arm randomized phase II study of durvalumab alone or with savolitinib or tremelimumab in previously treated advanced clear cell renal cancer. T Powles, MJ Mendez-Vidal, A Rodriguez-Vida, et al
4504 Cabozantinib (C) in combination with atezolizumab (A) in urothelial carcinoma (UC): Results from Cohorts 3, 4, 5 of the COSMIC-021 study. SK Pal, N Agarwal, P Singh, et al
Take-Home Message
- Cabozantinib, a multitargeted receptor TKI, and atezolizumab, an anti–PD-LI agent, had promising clinical activity in patients with inoperable locally advanced or metastatic urothelial carcinoma. The combination was studied as first-line systemic therapy in patients eligible or ineligible for cisplatin-based chemotherapy who had no prior therapy and as second-line or later in patients who had received one prior ICI and no prior VEGFR-TKI.
- Toxicity was manageable.
LBA4505 A randomised, double blind, phase II clinical trial of maintenance cabozantinib following chemotherapy for metastatic urothelial carcinoma (mUC): Final analysis of the ATLANTIS cabozantinib comparison. RJ Jones, SA Hussain, AJ Birtle, et al
4508 Final clinical results of pivotal trial of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive CIS and papillary nonmuscle-invasive bladder cancer (NMIBC). K Chamie, SS Chang, M Gonzalgo, et al
Take-Home Message
- This multicenter study of patients with high-grade non–muscle-invasive bladder cancer unresponsive to BCG looked at the efficacy and safety of intravesical BCG plus Anktiva (N-803). Among the 160 participants enrolled, 77 have papillary disease and 83 have carcinoma in situ. At 2 years, 90% of participants have avoided cystectomy, and overall bladder cancer–specific survival is 99%. At a median of 24.1 months’ duration of response, the complete response rate is 71% in patients with carcinoma in situ. The disease-free survival rate is 53% at 18 months in patients with papillary disease.
- The combination of Anktiva and BCG exceeds other intravesical and systemic treatment options in terms of safety and efficacy for patients with non–muscle-invasive bladder cancer.
Poster Session: Genitourinary Cancer—Kidney and Bladder
Saturday, June 4, 2022; Starting at 2:15 PM EDT
4559 Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): Long-term outcomes from JAVELIN Bladder 100 in subgroups defined by response to 1L chemotherapy. B Pérez-Valderrama, T Powles, SS Sridhar, et al
4577 Defining “platinum-ineligible” patients with metastatic urothelial cancer (mUC). S Gupta, J Bellmunt, ER Plimack, et al
Poster Discussion Session: Genitourinary Cancer—Kidney and Bladder
Saturday, June 4, 2022; 5:30 PM–7:00 PM EDT
4509 Phase 1 LITESPARK-001 (MK-6482-001) study of belzutifan in advanced solid tumors: Update of the clear cell renal cell carcinoma (ccRCC) cohort with more than 3 years of total follow-up. E Jonasch, TM Bauer, KP Papadopoulos, et al
4510 Characterization of the microbial resistome in a prospective trial of CBM588 in metastatic renal cell carcinoma (mRCC) offers mechanism for interplay between antibiotic (abx) use and immune checkpoint inhibitor (ICI) activity. N Dizman, LA Meza, PG Bergerot, et al
Take-Home Message
- Receipt of antibiotic therapy close to the administration of ICIs has been shown in experimental and observational studies to negatively impact tumor response to the ICI therapy. In this study, patients newly diagnosed with metastatic RCC were randomized to ICI therapy (nivolumab/ipilimumab) or to ICI plus the live bacterial product CBM588 to determine if the addition of CBM588 could facilitate ICI response. Among the 29 patients in the final analysis, the objective response was 20% in the nivolumab/ipilimumab arm (19 patients) and 58% in the nivolumab/ipilimumab plus CBM588 arm (10 patients). Although the overall abundance of antibiotic resistance genes was stable between baseline and week 12 in the patients receiving nivolumab/ipilimumab alone, there was a decrease in antibiotic resistance genes in the CBM588 arm from baseline to week 12.
- This study puts forth the hypothesis that combining antibiotics with the live bacterial product CBM588 may improve the response to immune checkpoint inhibitors.
4512 Adjuvant pembrolizumab for postnephrectomy renal cell carcinoma (RCC): Expanded efficacy analyses from KEYNOTE-564. TK Choueiri, P Tomczak, SH Park, et al
4520 RC48-ADC for metastatic urothelial carcinoma with HER2-positive: Combined analysis of RC48-C005 and RC48-C009 trials. X Sheng, Z He, Y Shi, et al
Dr. Sumanta Pal, Clinical Professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, and Editor-in-Chief of the PracticeUpdate Center of Excellence for Renal Cell Carcinoma, recommends the following abstracts being presented at this year’s ASCO Annual Meeting, held June 3 through June 7, 2022, in Chicago and simultaneously online.
Oral Abstract Session: Genitourinary Cancer—Kidney and Bladder
Friday, June 3, 2022 | 3:45 PM–6:45 PM EDT
LBA4500 EVEREST: Everolimus for renal cancer ensuing surgical therapy—A phase III study (SWOG S0931, NCT01120249). CW Ryan, C Tangen, EI Heath, et al
4501 Association between depth of response (DepOR) and clinical outcomes: Exploratory analysis in patients with previously untreated advanced renal cell carcinoma (aRCC) in CheckMate 9ER. C Suárez, TK Choueiri, M Burotto, et al
Take-Home Message
- The association between depth of response and clinical outcomes was studied in patients with advanced RCC who received nivolumab plus cabozantinib versus sunitinib in this exploratory analysis of CheckMate 9ER. Overall, a larger proportion of patients who received nivolumab plus cabozantinib had deeper responses compared with those who received sunitinib. These responses were associated with a better progression-free survival rate at 12 months compared with sunitinib. Although in both arms better overall survival outcomes were associated with increasingly deeper responses, the overall survival rates and medians were comparable between the two arms.
- In CheckMate 9ER, deeper responses were gained by more patients who received nivolumab plus cabozantinib than by those who received sunitinib.
4502 The relationship between health-related quality of life (HRQoL) and clinical outcomes in patients with advanced renal cell carcinoma (aRCC) in CheckMate (CM) 214. D Cella, M Hamilton, SI Blum, et al
LBA4503 CALYPSO: A three-arm randomized phase II study of durvalumab alone or with savolitinib or tremelimumab in previously treated advanced clear cell renal cancer. T Powles, MJ Mendez-Vidal, A Rodriguez-Vida, et al
4504 Cabozantinib (C) in combination with atezolizumab (A) in urothelial carcinoma (UC): Results from Cohorts 3, 4, 5 of the COSMIC-021 study. SK Pal, N Agarwal, P Singh, et al
Take-Home Message
- Cabozantinib, a multitargeted receptor TKI, and atezolizumab, an anti–PD-LI agent, had promising clinical activity in patients with inoperable locally advanced or metastatic urothelial carcinoma. The combination was studied as first-line systemic therapy in patients eligible or ineligible for cisplatin-based chemotherapy who had no prior therapy and as second-line or later in patients who had received one prior ICI and no prior VEGFR-TKI.
- Toxicity was manageable.
LBA4505 A randomised, double blind, phase II clinical trial of maintenance cabozantinib following chemotherapy for metastatic urothelial carcinoma (mUC): Final analysis of the ATLANTIS cabozantinib comparison. RJ Jones, SA Hussain, AJ Birtle, et al
Poster Session: Genitourinary Cancer—Kidney and Bladder
Saturday, June 4, 2022; Starting at 2:15 PM EDT
4553 Preventing adverse events in patients with renal cell carcinoma treated with doublet immunotherapy using fecal microbiota transplantation (FMT): Initial results from perform a phase I study. R Fernandes, S Nair Parvathy, DS Ernst, et al
4555 Transcriptomic profiling identifies genomic markers associated with benefit from stereotactic body radiation therapy (SBRT) in oligoprogressive metastatic renal cell carcinoma (mRCC). ZB Zengin, A Govindarajan, R Muddasani, et al
Poster Discussion Session: Genitourinary Cancer—Kidney and Bladder
Saturday, June 4, 2022; 5:30 PM–7:00 PM EDT
4510 Characterization of the microbial resistome in a prospective trial of CBM588 in metastatic renal cell carcinoma (mRCC) offers mechanism for interplay between antibiotic (abx) use and immune checkpoint inhibitor (ICI) activity. N Dizman, LA Meza, PG Bergerot, et al
Take-Home Message
- Receipt of antibiotic therapy close to the administration of ICIs has been shown in experimental and observational studies to negatively impact tumor response to the ICI therapy. In this study, patients newly diagnosed with metastatic RCC were randomized to ICI therapy (nivolumab/ipilimumab) or to ICI plus the live bacterial product CBM588 to determine if the addition of CBM588 could facilitate ICI response. Among the 29 patients in the final analysis, the objective response was 20% in the nivolumab/ipilimumab arm (19 patients) and 58% in the nivolumab/ipilimumab plus CBM588 arm (10 patients). Although the overall abundance of antibiotic resistance genes was stable between baseline and week 12 in the patients receiving nivolumab/ipilimumab alone, there was a decrease in antibiotic resistance genes in the CBM588 arm from baseline to week 12.
- This study puts forth the hypothesis that combining antibiotics with the live bacterial product CBM588 may improve the response to immune checkpoint inhibitors.
4514 Impact of subsequent therapies in patients (pts) with advanced renal cell carcinoma (aRCC) receiving lenvatinib plus pembrolizumab (LEN + PEMBRO) or sunitinib (SUN) in the CLEAR study. MH Voss, T Powles, BA McGregor, et al
4516 Long-term outcomes in EV-301: 24-month findings from the phase 3 trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma. JE Rosenberg, T Powles, GP Sonpavde, et al
Take-Home Message
- The 24-month findings of a phase III trial of the antibody–drug conjugate enfortumab vedotin (EV) in patients with previously treated locally advanced or metastatic urothelial carcinoma (la/mUC) confirm the survival advantage versus standard chemotherapy evident in the 12-month interim analysis. At 24 months, the median overall survival was 12.91 months with EV compared with 8.94 months with chemotherapy, a significant 3.97-month advantage. EV also was associated with a longer progression-free survival of a median 5.55 months compared with the chemotherapy median of 3.71 months.
- Patients with previously treated la/mUC experience a significant benefit in survival compared with those treated with standard chemotherapy, with no new safety signals.
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