Association of survival and local radiotherapy to the bladder versus chemotherapy alone for patients with metastatic urothelial carcinoma (mUC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 413-413
Author(s):  
Benjamin Walker Fischer-Valuck ◽  
Sagar Anil Patel ◽  
Hiram Alberto Gay ◽  
John Paul Christodouleas ◽  
Paul Sargos ◽  
...  
Keyword(s):  
Overall Survival ◽  
Urothelial Carcinoma ◽  
Prospective Trial ◽  
Multivariable Analysis ◽  
World Population ◽  
Newly Diagnosed ◽  
Landmark Analysis ◽  
Metastatic Urothelial Carcinoma ◽  
The Impact

413 Background: Limited data exists on the role of local therapy for metastatic urothelial carcinoma of the bladder (mUC). Large database analysis have inherent limitations but can shed light on survival outcomes in a real-world population and in scenarios not easily studied in a randomized fashion. We hypothesized that in the NCDB, radiotherapy (RT) to the bladder plus chemotherapy (CT) would be associated with improved overall survival (OS) vs CT alone. Methods: We queried the NCDB for newly diagnosed mUC cases (cT1-4 N0-3 M1) from 2004-2015 treated with CT alone vs CT plus RT to ≥ 45 Gy to the bladder. Cystectomy patients were excluded. To account for lead time bias, we excluded patients with < 2 months of follow-up. Variables for multivariable analysis (MVA) and matching included: age, sex, Charlson-Deyo comorbidity index (CCI), cT/N stage, facility type/location, insurance, year of diagnosis, and number of CT agents. Overall survival (OS) was estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards analyses was performed. Propensity score matching (all variables) and exact matching (CCI score, age +/- 5 years, cT stage) was performed. Results: 4,459 patients with newly diagnosed mUC received either CT+ RT (n = 337) or CT alone (n = 4,122). Median follow-up was 10.7 months (range 2-144). Median RT dose was 57.6 Gy (IQR, 50.0– 63.0 Gy). Median OS for CT+RT was 13.8 (95% CI, 12.1-15.5) vs. 8.4 months (95% CI, 7.5-9.4) for CT (P < 0.0001). In MVA, RT was associated with improved OS (HR, 0.70; 95% CI, 0.62-0.79; P < 0.0001). Increasing age, comorbidity score, and cT-stage were associated with worse OS (P < 0.001). In subgroup analysis of patients without other comorbidities (CCI of 0), median OS for CT+RT was 14.4 (95% CI, 12.1-16.7) vs 11.1 months (95% CI, 10.7-11.5) for CT (P = 0.001). For patients with cT2-3N0 disease, median OS for CT+RT was 14.0 months (95% CI, 6.8-21.3) vs 10.9 months (95% CI, 10.1-11.7) for CT (P = 0.001). On propensity matched analysis (337 CT+RT and 337 CT patients), CT+RT was associated with improved OS (median 13.8 vs 8.5 months; P < 0.0001; MVA HR 0.59, 95% CI 0.50-0.69, P < 0.0001). On exact matched analysis (205 CT+RT and 205 CT patients), CT+RT was associated with improved OS (median 13.5 vs 9.9 months; P = 0.002; MVA HR 0.67, 95% CI 0.57-0.79, P = 0.002). Landmark analysis for patients living ≥6 months (median OS 16.3 vs 13.6 months, P = 0.004) and ≥12 months (median OS 22.2 vs 19.1 months, P = 0.029) demonstrated improved OS for CT+RT. Conclusions: In this large contemporary series, mUC patients treated with local RT plus CT had improved OS compared to CT alone. The magnitude of the effect persisted with matching and landmark analysis to try to mitigate the effect of selection bias, though we could not control for extent of metastatic disease. These findings are hypothesis-generating; a prospective trial evaluating the impact of bladder RT in mUC is warranted.

Effect of asymptomatic recurrence detection after nephroureterectomy on prognosis in patients with upper urinary tract urothelial carcinoma.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 364-364
Author(s):  
Shingo Hatakeyama ◽  
Takahiro Yoneyama ◽  
Yasuhiro Hashimoto ◽  
Takuya Koie ◽  
Chikara Ohyama
Keyword(s):  
Overall Survival ◽  
Urinary Tract ◽  
Urothelial Carcinoma ◽  
Tumor Recurrence ◽  
Patient Survival ◽  
Upper Urinary Tract ◽  
Symptomatic Recurrence ◽  
The Impact ◽  
Urinary Tract Urothelial Carcinoma

364 Background: It is unknown whether routine follow up with body computed tomography (CT) to detect asymptomatic visceral recurrence after nephroureterectomy improves patient survival. We accessed the impact of follow up with body CT on patient survival after nephroureterectomy. Methods: A total 212 nephroureterectomy for upper urinary tract urothelial carcinoma were performed at our hospital between Feb 1995 and Oct 2015. All patients had regular follow up with chest x-ray, urine cytology and cystoscopy every 3 to 6 months, blood biochemical test, and CT of the chest and abdomen every 6 to 12 months. Additional examinations were required for symptomatic recurrence. We investigated the first site and date of tumor recurrence. Overall survival in patients with recurrence stratified by the mode of diagnosis (asymptomatic vs. symptomatic) was estimated using the Kaplan-Meier methods and compared with the log rank test. Cox proportional hazard regression models were used to evaluate the impact of the mode of diagnosing recurrence on survival. Results: A total 43 patients (20%) experienced recurrence after surgery, of whom 31 (72%) were asymptomatic and 12 (28%) were symptomatic. The most common symptoms at recurrence were pain in 7, hematuria in 2 , appetite loss in 1 , edema in 1 , palpable mass in 1, general malaise in 1 patients. Overall survival was not significantly different between in patients with asymptomatic vs. symptomatic recurrence; however, survival after tumor recurrence were better in patients with asymptomatic recurrence (P = 0.033). Moreover, multivariate analysis showed symptomatic recurrence was selected as a risk factor for overall survival after recurrence. Conclusions: Routine oncological follow up after nephroureterectomy for early detection of asymptomatic visceral recurrence was associated with patient survival. Further study is necessary to establish the optimal follow up regimen balancing the benefit of asymptomatic detection with the increased cost of routine surveillance.

Stereotactic radiosurgery (SRS) for brain metastasis (BM) in hormone receptor positive (HR+) HER2 negative breast cancer (BC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1069-1069
Author(s):  
Akshara Singareeka Raghavendra ◽  
Chao Gao ◽  
Fuchenchu Wang ◽  
Ran An ◽  
Yan Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Salvage Therapy ◽  
Brain Lesion ◽  
Multivariable Analysis ◽  
Karnofsky Performance Score ◽  
Performance Score ◽  
Risk Of Death ◽  
The Impact

1069 Background: With the increase of the utilization of SRS for the treatment of oligometastatic BM over surgical reaction or whole brain radiation therapy (WBRT), we sought to evaluate the impact of SRS on overall survival in HR+Her2- BC and prognostic factors associated with SRS. Methods: We reviewed prospectively collected data in the electronic data bases of the breast medical, surgical and radiation oncology departments at MD Anderson cancer center. We aimed at identifying HR+HER2- BC patients who received upfront SRS for BM’s between 08/10/2009 and 02/27/2018.Overall survival was defined as the time from the first SRS to last follow-up/death. Multivariate analysis by the Cox proportional hazards regression analysis was performed to evaluate the prognostic factors (age at BM, stage, Karnofsky performance score (KPS), symptomatic BM, BM at 1stdistant metastatic presentation, extracranial Disease, treatment history, salvage therapy, number of brain lesion treated) of SRS that influenced survival. Results: A total of 125 patients were identified, and we are reporting on 68 with completed analysis. Median age at time of first SRS was 53.86 years. 51 patients of the 68 were deceased at the time of this analysis and 17 patients were alive at the time of last follow-up. 49 patients (72.06 %) presented with radiation necrosis after SRS; 36 patients (52.94 %) presented with BM as 1st distant metastasis including metastasis to other sites. Number of BM’s lesions <4 was 60 (88.2%) and >=4 was 7 (10.3%). The median follow-up from time of first SRS for survivors was 10.84 months. 24 (35.29%) received two or more sessions of SRS and the mean time between first and second SRS sessions for these patients was 14.24 months. Median time from first SRS to second SRS for ER+HER2− patients was 10.84 months (n = 24); on multivariable analysis, higher Karnofsky performance score (KPS) was associated with better survival compared to no salvage therapy. Patients with KPS>90 (p=0.005) had better survival and reduced the hazard by a factor of 0.33 (or 67%). Receiving SRS (p=0.0003) or SRS+WBRT (0.0001) as salvage therapy reduced the hazard (risk of death) by 86% and 85%, respectively. Conclusions: SRS is an effective treatment modality for HR+HER2- BM from BC. Patients who received SRS or SRS and WBRT, KPS >90 had better survival than patients who didn’t receive any salvage therapy. Updated data will be available at the time of the presentation.[Table: see text]

Continued Improvement in Survival in Multiple Myeloma and the Impact of Novel Agents

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3972-3972 ◽  
Author(s):  
Shaji K. Kumar ◽  
Angela Dispenzieri ◽  
Morie A Gertz ◽  
Martha Q Lacy ◽  
John A Lust ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Initial Therapy ◽  
Novel Agents ◽  
The Novel ◽  
Newly Diagnosed ◽  
Entire Cohort ◽  
The Past ◽  
The Impact

Abstract Abstract 3972 Background: The treatment paradigm for myeloma has undergone a dramatic shift in the past decade with the introduction of the novel agents and their application at every stage of the treatment. We and others had previously shown that survival of patients with myeloma had improved in the earlier half of the last decade and attributed this to a combination of novel therapies as well as increased use of stem cell transplant. It is not clear if this momentum in improving survival has been maintained. We examined the survival trends of patients with newly diagnosed myeloma seen within the past decade to examine this question. Patients and Methods: We studied 1056 patients with newly diagnosed myeloma, who were seen at Mayo Clinic between January 1, 2001 and December 31, 2010; who were seen within 30 days of their diagnosis. For examination of the time trends, we grouped the time interval into two five year periods, 2001–2005 and 2006–2010. Survival was estimated using Kaplan Meier method and survival curves were compared by log rank test. Impact of various prognostic factors was evaluated using Cox proportional hazards test. Results: The median age at diagnosis was 65 (range; 22–92), and 59% were male. The median estimated follow up for the entire cohort was 4.6 years (95% CI; 4.4, 4.9) and 57% of the patients were alive at last follow up. The median overall survival (OS) for the entire cohort was 5.4 years (95% CI; 5, 6.3). The overall survival for patients in the 2001–2005 group was 4.6 years compared with not reached for the 2006–2010 cohort (P< 0.001). The five-year estimated OS was 48% for the earlier group compared with 66% for the latter group. The estimated 1-year survival was 90% for the recent cohort compared with 83% for the earlier cohort, suggesting improvements in the early mortality. Interestingly, the improvement was predominantly seen in the older age group (>65 years; 49%). The 5-year survival of the older patients improved significantly from 31% (2001–2005) to 56% (2006–2010) (P<0.001). In contrast, among younger patients (≤65 years of age), the 5-year survival improved only marginally from 63% (2001–2005) to 73% (2006–2010) (P=NS). One or more novel agents (Lenalidomide, thalidomide or bortezomib) were used as part of initial therapy in 631 (62% of 1021 in whom treatment data was available). The OS among of this group was 7.3 years (95% CI; 5.9, NR) compared with 3.8 years (95% CI; 3.1, 4.6). In a multivariate model that included both use of novel agent and the year group, only the novel agent use was associated with improved survival suggesting that the improvement in the survival is related to the increased use of novel agents in the initial therapy. No significant differences were observed between the groups in terms of conventional prognostic factors. Conclusions: The current results confirm continued improvement in the overall survival of patients, even within the last 10 year period, and highlight the impact of initial therapy with novel agents. Most importantly, we demonstrate that the improved survival has primarily benefited older patients. Our study highlights that urgent need for additional new agents to provide further survival improvement for younger patients, and in order achieve a cure for this disease. Disclosures: Kumar: Merck: Consultancy, Honoraria; Celgene: Research Funding; Millennium: Research Funding; Novartis: Research Funding; Cephalon: Research Funding; Genzyme: Research Funding. Dispenzieri:Celgene: Research Funding; Millennium Pharmaceuticals, Inc.: Research Funding; Janssen Research & Development: Research Funding. Gertz:Binding Site: Honoraria.

Recombinant Human Erythropoietin May Negatively Influence Survival in Newly Diagnosed Patients with Multiple Myeloma: A Single Center Experience in 246 Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4814-4814
Author(s):  
Eirini Katodritou ◽  
Evgenia Verrou ◽  
Anastasia Banti ◽  
Vassiliki Gastari ◽  
Dimitra Mihou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Serum Creatinine ◽  
Serum Ferritin ◽  
Recombinant Human Erythropoietin ◽  
Newly Diagnosed ◽  
Human Erythropoietin ◽  
The Impact

Abstract Anemia is a common clinical problem in patients with multiple myeloma (MM), which adversely affects their quality of life. The administration of recombinant human erythropoietin (r-HuEPO) improves anemia in about 2/3 of patients. However, it has not been clarified if r-HuEPO has any beneficial or adverse impact on the overall survival, particularly in a clear population of MM patients. The aim of this study was to examine the impact of r-HuEPO administration on the overall survival of newly diagnosed patients with MM. Two hundred forty-six newly diagnosed symptomatic MM patients, 139 males and 107 females, with a median age of 67 years (range 29–90) were studied. R-HuEPO was administered according to standard criteria, when Hb levels were less than 10.5g/dl and it was titrated and discontinued when Hb level reached 13g/dl. The parameters evaluated for predicting survival were: Age, sex, Hb, platelets, bone marrow infiltration, serum creatinine, serum ferritin, ISS score, B2-microglobulin and r-HuEPO administration. Cox regression was used for the univariate and multivariate analysis. One hundred forty-two patients received r-HuEPO and 105 did not. The median duration of r-HuEPO administration was 6 weeks (range 4–10) and the median hemoglobin level of patients who received r-huEPO, was 9.2g/dl (range 7.3–10.5 g/dl). The median follow up was 31 months (range 1–231). The univariate analysis showed that, age, Hb, platelets, serum creatinine, serum ferritin, ISS score, B2-microglobulin and r-HuEPO administration predicted for survival (p<0.05). The multivariate analysis demonstrated that, age, ISS score and r-HuEPO administration were statistically significant for predicting overall survival (p<0.05). The median survival of patients in the r-HuEPO group was 22 months (SD 22.7mo) whereas in the group without r-HuEPO administration it was 40 months (SD 35.8mo) (p=0.02). These results, suggest that r-HuEPO administration may negatively influence overall survival in newly diagnosed patients with MM and therefore, within this context, it should be used with caution. The large number of exclusively MM patients with a long follow up included in this study, highlights the importance of these results.

Impact of pure versus mixed metastatic urothelial carcinoma (mUC) histology on response with immune checkpoint inhibitors (ICIs).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 479-479 ◽  
Author(s):  
Archana Agarwal ◽  
Amin Nassar ◽  
Gregory Russell Pond ◽  
Justine A. Barletta ◽  
Andres Acosta ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Response Rate ◽  
Cox Regression ◽  
Single Agent ◽  
Objective Response ◽  
Multivariable Analysis ◽  
Cox Regression Analysis ◽  
Upper Tract ◽  
Metastatic Urothelial Carcinoma ◽  
The Impact

479 Background: PD1/PD-L1 inhibitors have been evaluated in trials enrolling patients (pts) with pure urothelial or mixed urothelial histology containing non-urothelial components. However, any differential impact of pure vs. mixed urothelial histology on ICI benefit is unclear. We conducted a retrospective study to evaluate the impact of pure vs. mixed urothelial carcinoma histology on outcomes with ICIs in pts with metastatic urothelial carcinoma (mUC). Methods: We obtained data from 120 pts with mUC from a single institution (DFCI) who received ICI therapy. Demographic, clinical variables and outcomes (overall response rate [ORR], overall survival [OS]) were collected. Histology was reviewed at DFCI for all pts and recorded as pure urothelial if only urothelial carcinoma was seen or mixed urothelial if components of any other histology were observed in addition to urothelial. A Cox regression analysis was done to study the association of prognostic variables and histology with objective response. Results: Data was obtained from 120 pts, of whom 110 (91.7%) received a single agent PD1/PD-L1 inhibitor (pembrolizumab=58, atezolizumab=52, nivolumab=4, nivolumab + ipilimumab=3, nivolumab + vaccine=2, durvalumab+tremelimumab=1). The median age was 66, 70.8% were male and 72.5% had received prior chemotherapy. 79 (65.8%) tumors originated from the bladder, 39 (32.5%) from the upper tract, 2 (1.67%) had unknown site of origin. 91 (76.6%) had pure urothelial and 28 (23.3%) had mixed urothelial histology. On univariable analysis, pure vs. mixed urothelial histology was not associated with response (HR 1.52 [95% CI 0.59-3.98, p=0.39]). On multivariable analysis, upper tract vs. bladder primary (HR 3.06 [95% CI 1.10-8.49], p=0.032) and higher blood neutrophil to lymphocyte ratio (HR 0.35 [95% CI 0.17-0.72], p=0.004) were associated with lower response rate. Conclusions: In this hypothesis-generating study, pure vs. mixed urothelial carcinoma histology did not appear to significantly impact response to ICI therapy for mUC. The impact of proportion of non-urothelial histology, pure non-urothelial histology and site of primary on response warrants further study.

scholarly journals Addition of rituximab to hyper-CVAD improves overall survival in newly diagnosed Burkitt leukemia/lymphoma from the Middle East and North Africa region

2019 ◽  
Vol 6 (10) ◽  
pp. 4199
Author(s):  
Najla S. Bin Sabbar ◽  
Fatimah S. Alowirdi ◽  
Fatimah A. Basakran ◽  
Lujain A. Al-Badr ◽  
Rawan A. Assiri ◽  
...  
Keyword(s):  
Overall Survival ◽  
Middle East ◽  
North Africa ◽  
Newly Diagnosed ◽  
Mena Region ◽  
Entire Cohort ◽  
Therapy Regimen ◽  
Significant Difference ◽  
The Impact

Background: Burkitt leukemia/lymphoma (BL) is a highly aggressive malignancy treated with intensive combinational chemotherapy. However, there is paucity in the literature with regards to outcome in patients with BL from the Middle East and North Africa Region (MENA).Methods: We examined the impact of incorporation of the monoclonal antibody rituximab within a chemotherapy backbone of hyper-fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, cytarabine and methotrexate (hyper-CVAD). Between 2007 to 2016, a total of 21 patients were identified and data retrospectively collected with median follow up was 32 months (1.1-120). The cohort was stratified based on exposure to rituximab and there was no significant difference regarding gender, age, stage, presence of constitutional symptoms, baseline presenting blood counts and proportion of patients completing prescribed therapy regimen between the strata.Results: Estimated overall survival (OS) of the entire cohort at 2 years was 71.1%; however, patients who received rituximab in conjunction with hyper-CVAD had a statistically significant improvement in 2-year OS at 81.2% vs 40% (p=0.048).Conclusions: In conclusion, we observed that incorporation of rituximab within a hyper-CVAD backbone improved OS in BL patients from the MENA region. These results warrant further evaluation.

Increased Number of High Dose Methotrexate Cycles and the Addition of Rituximab Is Associated with Better Outcomes in a Large Primary CNSL Cohort

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4125-4125
Author(s):  
Prakirthi Yerram ◽  
Samantha Nicole Reiss ◽  
Lisa Modelevsky ◽  
Lauren Schaff ◽  
Anne Reiner ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcomes ◽  
Multivariable Analysis ◽  
Standard Of Care ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Newly Diagnosed ◽  
Historical Cohort ◽  
Dose Methotrexate

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive primary brain tumor confined to the brain, eyes, and cerebrospinal fluid. Over the past few decades, prognosis for PCNSL has significantly improved due to the standard use of high dose methotrexate (MTX) containing treatment regimens. However, it remains unclear if the number of MTX doses and the addition of rituximab has an impact on clinical outcomes. The recent HOVON 105/ALLG NHL 24 study questioned the role of rituximab in the first line setting when combined with a MTX based polychemotherapy using only 4 doses of MTX and 6 doses of rituximab. Over the last 30 years, standard of care at Memorial Sloan Kettering Cancer Center (MSKCC) has evolved, allowing the comparison of patients receiving different numbers of MTX doses and those treated with and without rituximab. The purpose of this study was to describe clinical outcomes based on standard of care treatment changes. Methods: This single-center retrospective IRB approved study at MSKCC included patients with immunocompetent PCNSL, age ≥18 years and diagnosed between 1/1983-11/2017. Patients were identified through a departmental database and electronic medical record. The primary objective was to describe overall survival (OS) based on common prognostic markers such as age, KPS, MSKCC prognostic score class (RPA I- III), use of rituximab, and number of methotrexate cycles. Overall survival was calculated from the date of diagnosis to death or last follow-up using Kaplan-Meier methodology. When examining effect of MTX on OS, OS was calculated from date of last MTX cycle until death or last follow-up. Univariable and multivariable analysis for prognostic factors were analyzed using Cox proportional hazards regression. Results: Five hundred and forty-six patients with newly diagnosed PCNSL were identified. Median age at diagnosis was 62 (range 19 to 90), median KPS was 70 (range 10 to 100), and 282 (52%) were men. In total, 472 patients (86.4%) received high dose MTX. Of 460 with known number of MTX cycles, 95 (20.7%) received 1-4 cycles and 365 (79.3%) received ≥5 cycles (5 cycles: 189, 41.1%, 6 cycles: 24, 5.2%, 7 cycles: 74, 16.1%, 8+ cycles: 78, 17%). Rituximab was given to 231 (42.3%). Three hundred and ten (56.8%) patients, treated before 2006, had been reported previously (historic cohort) and 236 (43.2%) served as contemporary cohort. Median OS of the entire population was 4.7 years (95% CI: 3.8-5.7); 3.3 years (95% CI: 2.8-4.1) in the historic and 8.1 years (95% CI: 6.6-no upper limit) in the contemporary cohort. Five-year OS was 40.3% (95% CI: 35.1-46.2) for the historical cohort and 61.8% (95% CI: 55.0-69.5) for the contemporary cohort. Median OS in the contemporary cohort improved in all RPA classes in comparison to patients treated before 2006 (RPA I: not yet reached vs 9.2 years; RPA II: 7.6 years vs 3.5 years; RPA III 2.8 years vs 1.0 year) (Fig. 1). For the historical cohort compared to the contemporary cohort, five-year OS changed from 62.8% to 91.0% in RPA I, 42.0% to 63.0% in RPA II, and 16.3% to 36.9% in RPA III. Patients receiving ≥ 6 cycles of MTX had a better clinical outcome (median OS from last MTX cycle: 7.8 years versus 4.3 years; HR 0.68 (95% CI (0.51 - 0.91), p=0.0085) on multivariable analysis adjusted for age, KPS, sex, RPA classes Additionally, the stratification of rituximab further elucidated the association between MTX cycles and OS, such that in patients receiving rituximab, those treated with ≥ 6 cycles of MTX experienced longer median OS compared to patients receiving &lt; 6 cycles of MTX (13.0 years vs 9.4 years, p=0.001). Furthermore, in patients receiving ≥ 6 cycles of MTX, there was a survival benefit seen in patients who received rituximab compared to those who did not receive rituximab (13.02 years vs 1.61 years, p&lt;000.1) (Fig.2). Conclusions: Overall survival for newly diagnosed PCNSL has improved significantly over the last few decades regardless of age, KPS, RPA class. Patients seem to benefit with the addition of rituximab and when receiving 6 or more cycles of MTX. Disclosures Grommes: BTG: Consultancy; Kite: Consultancy; Squipps: Speakers Bureau.

scholarly journals Alterations in DNA Damage Response and Repair Genes as Potential Marker of Clinical Benefit From PD-1/PD-L1 Blockade in Advanced Urothelial Cancers

2018 ◽  
Vol 36 (17) ◽  
pp. 1685-1694 ◽  
Author(s):  
Min Yuen Teo ◽  
Kenneth Seier ◽  
Irina Ostrovnaya ◽  
Ashley M. Regazzi ◽  
Brooke E. Kania ◽  
...  
Keyword(s):  
Dna Damage ◽  
Overall Survival ◽  
Urothelial Carcinoma ◽  
Dna Damage Response ◽  
Response Rate ◽  
Objective Response ◽  
Multivariable Analysis ◽  
Long Term Outcome ◽  
Damage Response ◽  
Metastatic Urothelial Carcinoma

Purpose Alterations in DNA damage response and repair (DDR) genes are associated with increased mutation load and improved clinical outcomes in platinum-treated metastatic urothelial carcinoma. We examined the relationship between DDR alterations and response to PD-1/PD-L1 blockade. Methods Detailed demographic, treatment response, and long-term outcome data were collected on patients with metastatic urothelial carcinoma treated with atezolizumab or nivolumab who had targeted exon sequencing performed on pre-immunotherapy tumor specimens. Presence of DDR alterations was correlated with best objective response per Response Evaluation Criteria in Solid Tumors (RECIST) and progression-free and overall survival. Results Sixty patients with urothelial cancer enrolled in prospective trials of anti-PD-1/PD-L1 antibodies met inclusion criteria. Any DDR and known or likely deleterious DDR mutations were identified in 28 (47%) and 15 (25%) patients, respectively. The presence of any DDR alteration was associated with a higher response rate (67.9% v 18.8%; P < .001). A higher response rate was observed in patients whose tumors harbored known or likely deleterious DDR alterations (80%) compared with DDR alterations of unknown significance (54%) and in those whose tumors were wild-type for DDR genes (19%; P < .001). The correlation remained significant in multivariable analysis that included presence of visceral metastases. DDR alterations also were associated with longer progression-free and overall survival. Conclusion DDR alterations are independently associated with response to PD-1/PD-L1 blockade in patients with metastatic urothelial carcinoma. These observations warrant additional study, including prospective validation and exploration of the interaction between tumor DDR alteration and other tumor/host biomarkers of immunotherapy response.

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