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  • Ghosh, Sunita  (9)
  • Heng, Daniel Yick Chin  (9)
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. 406-406
    Abstract: 406 Background: HDC-ASCT is a standard therapy for patients (pts) with mGCTs whose disease progresses on or after conventional dose chemotherapy. We conducted a retrospective review of HDC-ASCT in pts with relapsed mCGT in Alberta over the past two decades. Methods: Pts with mGCTs who received HDC-ASCT at two provincial referral cancer centers in Alberta, Canada from 2001-2018 were identified. Baseline clinical and treatment characteristics were collected as well as overall survival (OS) and disease-free survival (DFS). Relevant prognostic variables were analyzed. Results: Forty three pts were identified. Median age was 28 years (range 19 – 56). Majority (95%) had non-seminoma histology and testis/retroperitoneal primary (84%). Twenty pts (47%) had poor risk disease as per IGCCC at start of first-line chemotherapy. HDC-ASCT was used as second-line therapy in 65% and 58% received tandem HDC-ASCT. Median follow-up from ASCT was 22 months (range 2 – 181). At last follow-up, 42% of pts are alive without disease, including 3/7 (43%) of pts with primary mediastinal disease. Two-year and 5-year DFS/OS were 44%/51% and 41%/43%, respectively. Median OS and DFS for all pts were 27.9 months (10.2 – NR) and 9.3 months (4.2 – 124), respectively. Conclusions: We found that HDC-ASCT is an effective salvage therapy in mGCT, consistent with existing literature. Pts appeared to benefit regardless of primary site. Though limited by small sample size, we found a numerical difference in DFS and OS between 2nd and 3rd line HDC-ASCT and single vs. tandem ASCT.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 316-316
    Abstract: 316 Background: Cabozantinib (cabo) is an oral multi-targeted tyrosine kinase inhibitor (TKI) with activity in mRCC. TKI toxicity, an indicator of adequate drug exposure, has been associated with clinical effectiveness for sunitinib, pazopanib, and axitinib. We explored whether cabo dose reductions (a surrogate for toxicity) were associated with improved clinical outcomes in mRCC. Methods: Using the CKCis database, we performed an analysis of patients treated with cabo in the second-line or later between 2011-2021. We divided the cohort into those needing a dose reduction (DR, defined as less than the starting dose at time of treatment discontinuation) and those who did not (no-DR). We compared outcomes by dose reduction status, including objective response rate (ORR), time to treatment failure (TTF), and overall survival (OS). Results: We identified 260 patients who received cabo, of which 103 (41.0%) needed a DR. Across all lines, the ORR was similar between the DR and non-DR groups: 19.6% vs. 18.9% (p = 0.903) respectively. The median TTF was 12.75 months (95% CI 10.38 – 17.64) in the DR group vs. 6.44 months (95% CI 5.49 – 8.67) in the no-DR group. After adjusting for IMDC risk, the hazard ratio (HR) for TTF comparing DR vs. no-DR was 0.69 (95% CI 0.50 - 0.97, p-value = 0.03). The median OS was 29.6 months (95% CI 19.58 – 42.64) in the DR group vs. 15.28 (95% CI 11.04 – 22.64) in the no-DR group. After adjusting for IMDC risk, the HR for OS comparing DR vs. no-DR was 0.65 (95% CI 0.43 - 0.98, p = 0.04). Conclusions: Cabozantinib dose reductions, a surrogate for toxicity and adequate drug exposure, appear to be associated with improved TTF and OS in mRCC. Toxicity driven/individualized dosing strategies for cabo alone and in combination with immunotherapy, warrant further investigation.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. 682-682
    Abstract: 682 Background: Cabozantinib is a multitargeted tyrosine kinase inhibitor (TKI) that has demonstrated efficacy in mRCC randomized trials. Less is known about the activity of cabozantinib in patients (pts) exposed to immuno-oncology (IO) agents. We explored the real-world effectiveness of cabozantinib, including in pts who had progressed on IO therapy. Methods: Using CKCis, a prospective Canadian database, pts treated with cabozantinib monotherapy as second-line or later were identified. Baseline clinical and treatment characteristics were collected. Rates of partial response (PR), stable disease (SD), progressive disease (PD) and disease control (DCR, PR+SD) were determined along with median time to treatment failure (mTTF) and median overall survival (mOS). Results: A total of 156 pts were identified. Median age was 62 years (range 21-84), 74% of pts had clear-cell histology, and 54% had 〉 3 sites of metastases (12% in CNS, 47% in bone). At time of cabozantinib start, 34% had KPS score 〈 80. Outcomes are described below. Conclusions: The effectiveness of cabozantinib observed in this real-world population was consistent with results from clinical trials. Cabozantinib also appears to provide benefit to mRCC pts who have progressed on prior IO therapy, and should be incorporated into contemporary treatment algorithms. Further follow up is ongoing.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 304-304
    Abstract: 304 Background: Current treatment principles for advanced nccRCC have been largely extrapolated from guidelines for clear cell RCC. Given the emerging randomized data for select nccRCC subtypes, real-world outcomes for these patients are informative particularly in the contemporary checkpoint inhibitor era. Methods: We performed an analysis using the Canadian Kidney Cancer information system (CKCis), a prospective database involving 14 academic centers, on nccRCC patients undergoing first-line systemic therapy between January 2011 – December 2019. Treatment groups were defined as receipt of: vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGF-TKI), mammalian target of rapamycin inhibitors (mTORi), and PD-1/PD-L1 immune checkpoint inhibitors (ICI, mono- or combination therapy). Primary outcome was 1-yr overall survival (OS) rate. Secondary outcomes were median time to treatment failure ((TTF, months), defined as treatment discontinuation, change or death) and objective response rate (ORR, %). Results: We identified 265 nccRCC patients: 204 (77.0%) received VEGF-TKI, 19 (7.2%) received mTORi and 42 (15.8%) received ICI-based first-line therapy (Table). Overall, median age was 64 years, 75% were male, 84% were classified as IMDC intermediate/poor risk, and 16% underwent prior nephrectomy. Twenty-three percent of patients were enrolled in clinical trials. Patients received primarily sunitinib (81%) or pazopanib (15%) in the VEGF-TKI group (other: 4%), while mTORi-treated patients received temsirolimus (74%) or everolimus (26%). For the ICI-based treatment group, most patients received combination therapy as ipilimumab-nivolumab (71%) or pembrolizumab-axitinib (26%), with 3% receiving ICI monotherapy. 1-yr OS was 65.2% for VEGF-TKI, 57.9% for mTORi and 69.0% for ICI-treated patients. Median TTF was 3.3 for VEGF-TKI, 3.5 for mTORi and 7.1 mos for ICI-treated patients. ORR was 17%, 5%, and 37% respectively for the VEGF-TKI, mTORi and ICI-treated groups. Conclusions: We describe the effectiveness of first-line therapy for patients with nccRCC from a national database. This real-world data suggests an association between first-line ICI-based therapies and improved outcomes, albeit with cabozantinib not available for the indication during this time. Our data supports consensus recommendations for preferred use of ICI-based or VEGF-TKI over mTORi as first-line therapy in nccRCC.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. 633-633
    Abstract: 633 Background: I+N is now standard of care for first line treatment of intermediate/poor risk mRCC patients (pts). Real world data is vital to understand drug usage, toxicity and outcomes in non-trial pts. This project describes the amount and tolerability of treatment delivered including discontinuation rates, reasons for discontinuation and outcomes from the CKCis database. Methods: Pts in CKCis, a prospective Canadian database from 15 academic centers, who received first line I+N were included. The number of doses of I+N, number of pts who received single-agent nivolumab (N) and duration of single agent N were determined. Reasons for treatment discontinuation, including the rate, type, and grade of toxicities were identified. Efficacy outcomes included time to failure (TTF – time to progression, death, or second line therapy), overall response rate (ORR) and overall survival (OS). Results: The cohort consists of 182 pts. Median age was 63 yrs, 71% had clear cell histology, 11% were on a clinical trial, the IMDC risk distribution was 5% good, 63% intermediate, 32% poor. Median follow up was 8.8 m. All 4 I+N doses were received by 30% of pts of which 78% went on to receive single-agent N. Less than 4 doses of I+N were received by 70% of pts of which 28% went on to receive single-agent N. The median time on single agent N was 5.7 m. In the entire cohort, 21% of patients discontinued therapy due to toxicity. The most common toxicity events were colitis (56% of all events), pneumonitis (19%), and hepatitis (8%). There were no toxicity-related deaths. Median OS has not been reached (22 events to date). Median TTF was 12.4 m. ORR was 32% (5% complete responses). 26% of pts received second line treatment, the most common being sunitinib in 79%. Conclusions: In this real world cohort, the majority of mRCC pts did not receive all 4 doses of I+N, contrasting with clinical trial reporting, yet many of these pts went on to receive single agent N. Discontinuation rates due to toxicity were similar to those reported in CheckMate 214. Further follow up is ongoing and efficacy outcomes analyzed on the basis of treatment quantity/duration will be presented.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. 620-620
    Abstract: 620 Background: Up to one-third of patients with mRCC can present with asymptomatic brain metastases (BM). Timely identification of BM allows for the delivery of early local interventions, which may lead to improved patient outcomes. To investigate the potential utility of routine intra-cranial imaging, we compared the outcomes of mRCC patients with asymptomatic versus symptomatic BM. Methods: Using the Canadian Kidney Cancer information system (CKCis) database, we identified mRCC patients diagnosed with BM between 2011 and 2018. This cohort was divided into two groups dependent on the presence or absence of neurological symptoms. Baseline patient demographics, clinico-pathological disease characteristics and survival data were extracted. Statistical analysis was through chi-square tests, analysis of variance and Kaplan-Meier method to characterize survival outcomes. Results: 269 mRCC patients with BM were identified with the majority presenting with symptomatic disease (n=163; 61%). No significant differences in clinico-pathological disease characteristics were identified. Median overall survival (OS) from mRCC diagnosis for asymptomatic patients was 33.4 months (interquartile range, IQR 27.8-64.4) versus 34.5 months (20.4-43.4) for symptomatic patients (p=0.35). Median OS from time of BM diagnosis revealed a trend favoring asymptomatic, as compared to symptomatic, patients [24.5 (17.6-24.9) vs. 13.1 months (9.0-20.6), p=0.06]. Factors associated with worse OS from time of BM diagnosis included presentation with symptomatic BM [hazard ratio, HR (95% CI): 1.40 (1.03-1.90), p=0.034] and International Metastatic Renal Cell Carcinoma Consortium Database (IMDC)-characterized intermediate/poor risk disease [HR (95% CI): 1.47 (1.01-2.13), p=0.045]. Conclusions: Routine intra-cranial imaging may lead to earlier identification of BM in mRCC. However, further investigation as to whether this practice improves survival is warranted.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 568-568
    Abstract: 568 Background: While the use of CPI has demonstrated clinical benefit in patients with mRCC, data showing the efficacy of subsequent TT is limited. This real-world analysis evaluated the efficacy of TT post CPI in mRCC patients. Methods: Data was collected and analyzed from CKCis. Patients with mRCC who received TT after CPI were identified and analyzed based on line of therapy. Time to treatment failure (TTF – time from starting first subsequent TT to stopping TT) and overall survival (OS) were calculated. Hazard Ratio (HR) calculations were adjusted for IMDC group and age. Results: 102 patients were treated with TT post CPI (table). Those who received first-line ipilimumab + nivolumab (I/N) versus a vascular endothelial growth factor inhibitor (VEGFi) + CPI combination prior to second-line TT had a median TTF of 8.0 vs 5.2 months (m) (HR=0.43, 95% CI: 0.13-1.44) and median OS of 16.5 m vs not reached (HR=0.76, 95% CI: 0.11-5.24). Patients who received a VEGFi versus a mammalian target of rapamycin inhibitor (mTORi) as third-line TT had a median TTF of 7.6 vs 4.4 m (HR=0.52, 95% CI: 0.24-1.10) and median OS of 21.7 vs 16.2 m (HR=0.41, 95% CI: 0.16-1.08). All third-line TT patients received first-line VEGFi and second-line nivolumab. Of the third-line VEGFi TT patients, 24 received axitinib (TTF 7.1 m, OS 21.7 m) and 22 received cabozantinib (data immature). Conclusions: Activity of TT in mRCC patients after CPI is demonstrated in multiple lines. In second-line, VEGFi TT had numerically better outcomes after I/N than after VEGFi+CPI combination. Efficacy of third-line TT was seen with a trend favoring VEGFi over mTORi. Axitinib in the third-line has notable activity after CPI, while data on cabozantinib and fourth-line TT are maturing. These results support the use of VEGFi after CPI in mRCC patients. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 4516-4516
    Abstract: 4516 Background: Active surveillance (AS) is a commonly used strategy in patients (pts) with low tumor burden or slow growing disease. However, few studies have assessed AS for mRCC compared to immediate treatment. We aimed to assess the outcomes and safety of AS in comparison to immediate systemic treatment for mRCC pts. Methods: Using CKCis, mRCC pts diagnosed between January 1, 2011 and December 31, 2016 were identified. AS strategy was defined as: (1) start of systemic therapy ≥6 months after diagnosis of mRCC; or (2) never receiving systemic therapy for mRCC with an overall survival (OS) ≥1 yr (OS ≥ 1 yr a surrogate to exclude pts not started on treatment due to poor prognosis). Pts starting systemic treatment 〈 6 months after diagnosis of mRCC were defined as receiving immediate systemic treatment. OS and time until 1 st line treatment failure (TTF) between the two cohorts were compared. Results: A total of 863 pts met criteria for AS (cohort A). Of these, 370 started treatment ≥ 6 months after their initial diagnosis (cohort A1) and 493 never received systemic treatment and were alive for ≥1 year (cohort A2). 848 pts received immediate systemic treatment (cohort B). Median age for pts in cohort A and B was 65.1 (19.0-91.5) vs. 62.2 yrs (23.1-87.1) (p 〈 0.0001). Sex distribution was not statistically different. Pts in cohort A had fewer sites of metastatic disease vs. cohort B ( 〈 0.0001) and 23% of pts in cohort A had metastasectomy vs. 5% in cohort B (P = 〈 0.0001). Five-year OS probability was significantly greater for cohort A than for cohort B (70.2% vs. 32.1%; P 〈 0.0001). After adjusting for IMDC risk criteria and age, both OS (HR 0.46, 0.38-0.56, P 〈 0.0001) and TTF (HR 0.79, 0.69-0.92, P = 0.0021) were greater in cohort A1 vs. B. For cohort A1 the median time on AS was 14.2 m (range 6 – 71). Conclusions: Based on the largest analysis of AS in mRCC to date, our data suggest that a subset of pts may be safely observed without immediate initiation of systemic therapy. Prospective validation is required in the contemporary immunotherapy era.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 346-346
    Abstract: 346 Background: The use of I/N is a proven first-line option for patients with intermediate/poor IMDC prognostic criteria. The use of vascular endothelial growth factor inhibitors such as sunitinib have shown activity in the treatment of ccmRCC, but their effectiveness post I/N needs better characterization. This study aims to demonstrate the efficacy of sunitinib, and other TKI agents post I/N in ccmRCC in a real world setting. Methods: Patients with ccmRCC who had received I/N and were subsequently treated with TKI between Jan 1, 2011 and December 31, 2019 were identified from CKCis. Time to treatment failure (TTF – time from start of first subsequent TKI to discontinuation for any reason) and overall survival (OS) – time from first subsequent TKI to death) were calculated using the Kaplan-Meier method. Cox regression was performed to adjust for IMDC criteria. RECIST criteria was used to determine best overall response (ORR) of TKI radiographically. Results: 64 patients were treated with TKI post I/N. Characteristics and outcomes are listed in the table. Of the second-line TKI patients, 51 received sunitinib, 10 received pazopanib and 3 received other TKI. Reasons for second-line TKI discontinuation are: 28% toxicity, 34% progression, 7% other reasons while 31% remain on treatment. Median follow-up time was 12.9m. ORR for second-line TKI overall and second-line sunitinib was 30.0% and 29.4%, respectively. Conclusions: These data show that TKI are active after I/N in ccmRCC. TTF may underestimate PFS due to the large number of patients discontinuing treatment for toxicity and not progression. Efficacy of second-line TKI post I/N in this dataset is similar that of first-line sunitinib from recent randomized phase III trials, suggesting that there may be no significant loss of TKI activity after having received first-line I/N. Overall, these data support the use of TKI after I/N.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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