Influence of first-line chemotherapy regimen on survival outcomes of patients with advanced urothelial carcinoma who receive second-line immunotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4535-4535
Author(s):  
Benjamin Miron ◽  
Elizabeth A. Handorf ◽  
Kevin Zarrabi ◽  
Matthew R. Zibelman ◽  
Pooja Ghatalia ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Cox Regression ◽  
Smoking Status ◽  
Performance Status ◽  
Single Agent ◽  
Second Line ◽  
First Line ◽  
Real World Data ◽  
Advanced Urothelial Carcinoma ◽  
Platinum Chemotherapy

4535 Background: Treatment of advanced urothelial carcinoma (mUC) has improved following approvals of PD-1/PD-L1 inhibitors. Platinum chemotherapy remains the standard-of-care in the first-line (1L). Cisplatin (Cis) regimens are accepted to be superior to carboplatin (Carbo) regimens for patients (pts) who are Cis-eligible. We sought to evaluate if differences in efficacy of 1L Cis vs. Carbo have meaningful impact on overall survival (OS) in the era of second-line (2L) immunotherapy (IO). Methods: We conducted a retrospective, observational cohort study to compare OS for pts treated with 1L Cis or Carbo combined with gemcitabine (Gem) followed by 2L IO using patient-level data from the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Pts included were diagnosed with mUC between 9/1/2015 and 9/15/2020. 2L IO was defined as single-agent atezolizumab, avelumab, durvalumab, nivolumab, or pembrolizumab. OS was calculated from start of 1L and 2L therapy and compared using Kaplan-Meier curves. Time to 2L IO was calculated from start of 1L to start of IO. Adjusted OS was calculated using multivariable Cox regression models, adjusting for age, gender, race, ECOG performance status, primary site, prior cystectomy, smoking status, and year of diagnosis. Results: A total of 1882 pts were included, 924 (49.1%) received Gem/Cis and 958 (50.9%) received Gem/Carbo in 1L. A similar percentage of pts did not receive any 2L therapy following Gem/Cis (46.4%) or Gem/Carbo (46.0%). Our analysis focused on the 780 pts (41.4%) who received 2L IO—381 after Gem/Cis and 399 after Gem/Carbo. Median follow-up time for the group was 35 months (mo). Pts in the Gem/Cis cohort were younger, had better performance status and lower incidence of upper tract disease (Table). OS from start of 1L therapy was numerically longer in pts who received Gem/Cis compared to Gem/Carbo on unadjusted (median 18.0 v 16.2 mo, p = 0.06) and adjusted analyses (HR = 0.83, 95% CI 0.69-1.00, p = 0.055) but neither result was statistically significant. Time to 2L IO was longer for pts receiving Gem/Cis (6.5 mo) vs Gem/Carbo (5.5 mo, p = 0.008). Survival time on 2L IO did not differ significantly by 1L regimen (Gem/Cis 8.0 mo vs Gem/Carbo 8.2 mo p = 0.36). Conclusions: Real world data suggests that in pts with mUC who are able to receive second-line IO, the choice of first-line platinum chemotherapy may not provide a distinguishable OS benefit. Despite methodologic limitations of this data, a greater focus in discussions with patients on toxicity associated with cisplatin vs carboplatin may be warranted.[Table: see text]

Real-World Clinical Outcomes of Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma

2020 ◽  
Author(s):  
Yoshifumi Kadono ◽  
Shohei Kawaguchi ◽  
Takahiro Nohara ◽  
Kazuyoshi Shigehara ◽  
Kouji Izumi ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Real World ◽  
Performance Status ◽  
Progression Free Survival ◽  
High Volume ◽  
Phase Iii ◽  
Second Line ◽  
Real World Data ◽  
Platinum Based Chemotherapy ◽  
Advanced Urothelial Carcinoma

Abstract Background: Pembrolizumab is currently considered the standard second-line treatment for advanced urothelial carcinoma (UC). This study aimed to investigate the efficacy and safety of pembrolizumab in patients with advanced UC in real-world data, which is not well-reported.Methods: The study included 98 patients with advanced UC who were treated with pembrolizumab after platinum-based chemotherapy at eight hospitals. The efficacy, safety, and risk factors for prognosis were evaluated. Results: The median age was 73 years. Nineteen patients (19%) with performance status (PS) 2-4 were included. The percentages of liver, lung, bone, and lymph node metastasis were 18%, 27%, 19%, and 76%, respectively. The best response was complete response in nine patients (9%) and partial response in 16 patients (17%). The median progression-free survival and overall survival were 3.7 months (95% confidence interval [CI]: 2.8–4.7) and 11.8 months (95% CI: 6.7–17.0), respectively. Poor PS, liver metastasis, and higher C-reactive protein were poor prognostic factors. Hyperprogression was observed in nine patients (9%), who were mostly of poor PS and had high-volume lesions. Severe adverse events (AEs) were observed in 18 patients (19%), and five patients died because of AEs (5%). Atypical AEs, such as pneumocystis pneumonia and acute myeloid leukemia, were observed in our cohort. Conclusion: The efficacy of pembrolizumab for advanced UC in our cohort was better than a previous phase III trial (KEYNOTE-045), possibly owing to lower cancer volume and fewer visceral metastases in our patients.

Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

1997 ◽  
Vol 15 (7) ◽  
pp. 2564-2569 ◽  
Author(s):  
S B Saxman ◽  
K J Propert ◽  
L H Einhorn ◽  
E D Crawford ◽  
I Tannock ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Combination Chemotherapy ◽  
Performance Status ◽  
Single Agent ◽  
Phase Iii ◽  
Long Term Follow Up ◽  
Intergroup Trial ◽  
Advanced Urothelial Carcinoma

PURPOSE A previously reported randomized intergroup trial demonstrated that combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was superior to single-agent cisplatin in patients with advanced urothelial carcinoma. We conducted a long-term analysis of patients included in the intergroup trial to examine factors associated with long-term survival. PATIENTS AND METHODS Two-hundred fifty-five assessable patients with urothelial carcinoma were randomized to receive either single-agent cisplatin (70 mg/m2 on day 1) or combination chemotherapy with methotrexate (30 mg/m2 on days 1, 15, and 22), vinblastine (3 mg/m2 on days 2, 15, and 22), doxorubicin (30 mg/m2 on day 2), and cisplatin (70 mg/m2 on day 2). Courses were repeated every 28 days. The association between patient characteristics and survival was assessed using Cox proportional hazards models. RESULTS With long-term follow-up evaluation, survival in the M-VAC arm continues to be superior to cisplatin (P = .00015, log-rank test). Predictors of survival include performance status, histology, and the presence of liver or bone metastasis. Only 3.7% of the patients randomized to M-VAC are alive and continuously disease-free at 6 years. CONCLUSION Long-term follow-up evaluation of the intergroup trial confirms that M-VAC is superior to single-agent cisplatin in patients with advanced urothelial carcinoma; however, durable progression-free survival is rare. Patients with non-transitional-cell histology, poor performance status, and/or bone or visceral involvement fare poorly and are unlikely to benefit significantly from M-VAC chemotherapy.

scholarly journals Second-line systemic therapies for metastatic urothelial carcinoma: a population-based cohort analysis

2019 ◽  
Vol 26 (2) ◽  
Author(s):  
E. S. Tsang ◽  
C. Forbes ◽  
K. N. Chi ◽  
B. J. Eigl ◽  
S. Parimi
Keyword(s):  
Urothelial Carcinoma ◽  
Systemic Therapy ◽  
Topoisomerase I ◽  
Cohort Analysis ◽  
Retrospective Chart Review ◽  
Population Based ◽  
Second Line ◽  
First Line ◽  
Real World Data ◽  
Line Setting

Introduction Patients with urothelial carcinoma (uc) have a poor prognosis after progression on first-line cisplatinbased chemotherapy. Real-world data about second-line cytotoxic therapies are limited. We sought to characterize patients with metastatic uc who receive more than 1 line of systemic therapy and to describe their treatments and outcomes.Methods Using BC Cancer’s pharmacy database, we identified patients with documented metastatic uc who had received more than 1 line of systemic therapy. A retrospective chart review was then performed to collect clinicopathologic, treatment, and outcomes data.Results The 51 included patients, of whom 42 were men (82%), had a median age of 65 years (range: 38–81 years). Sites of metastasis included lymph nodes (n = 30), bone (n = 7), lung (n = 9), and peritoneum (n = 2). Second-line chemotherapy regimens included gemcitabine–cisplatin [gc (n = 14)], paclitaxel (n = 24), docetaxel (n = 12), and an oral topoisomerase i inhibitor (n = 1). Median time to progression (ttp) and overall survival (os) were 2.0 and 6.83 months respectively. Compared with patients who received a different agent, patients who had experienced a prior response to first-line gc and who were re-challenged with second-line gc had a better median ttp (11.0 months vs. 6.0 months, p = 0.02) and survived longer (4.0 months vs. 1.0 months, p = 0.02). No differences in os between non-gc regimens were evident.Conclusions In patients with metastatic uc, overall outcomes remain poor, but compared with patients receiving other agents, the subgroup of patients re-challenged with second-line gc demonstrated improved ttp. Conventional chemotherapy regimens provide only modest benefits in the second-line setting and have largely been replaced with immunotherapy.

Phase II trial of paclitaxel and carboplatin in the treatment of advanced urothelial carcinoma.

1998 ◽  
Vol 16 (5) ◽  
pp. 1844-1848 ◽  
Author(s):  
B G Redman ◽  
D C Smith ◽  
L Flaherty ◽  
W Du ◽  
M Hussain
Keyword(s):  
Urothelial Carcinoma ◽  
Performance Status ◽  
Single Agent ◽  
Area Under The Curve ◽  
Total Bilirubin Level ◽  
Median Response ◽  
Treatment Delays ◽  
Eligibility Requirements ◽  
Advanced Urothelial Carcinoma ◽  
Dose Reductions

PURPOSE Both paclitaxel and carboplatin have single-agent activity against carcinoma of the urothelium. We evaluated the combination of paclitaxel and carboplatin in the treatment of advanced cancers of the urothelium. PATIENTS AND METHODS Patients with cancers of the urothelium who had no prior chemotherapy (prior adjuvant chemotherapy > 6 months allowed) were eligible for treatment. Eligibility requirements were performance status of 2 or less, creatinine level less than 2.0 mg/dL, granulocyte count (AGC) 1,500/microL or greater, platelet count 100,000/microL or greater, and total bilirubin level less than 1.5 mg/dL. Paclitaxel 200 mg/m2 followed by carboplatin (area under the curve [AUC] 5, Calvert formula) were administered every 21 days. Patients were evaluated for toxicity weekly and assessed for response every 6 weeks. RESULTS Thirty-six patients were entered onto the study and 35 patients were assessable for response. A total of 184 cycles were administered (median, six cycles per patient). Nine patients required one dose reduction, and seven patients required two dose reductions for a nadir AGC less than 500/microL, with only one episode of febrile neutropenia and sepsis. Myalgias and arthralgias of grades 1 to 2 occurred in 16 patients and usually lasted 2 to 3 days after treatment. There were no treatment delays because of toxicity. There were 18 responses; seven complete responses (CRs) and 11 partial responses (PRs) (response rate 51.5%; 95% confidence interval, 35 to 68). Median response durations for CR and PR were 6 and 4 months, respectively. Overall median survival was 9.5 months. CONCLUSION The combination of paclitaxel and carboplatin is an active and well-tolerated regimen for the treatment of advanced urothelial carcinoma. Because of the modest toxicity of this combination, paclitaxel and carboplatin should be considered for addition to other agents with activity in urothelial carcinomas.

Feasibility of sequential fixed S-1 followed by paclitaxel for the treatment of advanced or recurrent gastric cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15113-15113
Author(s):  
M. Ohashi ◽  
T. Kanda ◽  
K. Yajima ◽  
H. Honma ◽  
S. Kosugi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Treatment Time ◽  
Performance Status ◽  
Single Agent ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Chemotherapy ◽  
Recurrent Gastric Cancer ◽  
Line Chemotherapy

15113 Background: First-line chemotherapy for advanced/recurrent gastric cancer has limited efficacy, achieving a median survival time (MST) of about 7 months, while addition of second-line and subsequent chemotherapy may prolong MST to about 11.5 months. In practice, however, about half of patients failing with first-line chemotherapy are unable to receive second-line chemotherapy because of worsening of their performance status (PS), disease progression, or toxicities during protracted first-line chemotherapy. We studied the feasibility of a sequential fixed regimen devised to ensure prompt initiation of second-line chemotherapy after first-line failure. Methods: Between December 2002 and December 2006, patients with advanced or recurrent gastric cancer were enrolled who met the following requirements: 1) major organ function preserved; 2) PS 0–2; 3) presence of at least one evaluable lesion; and 4) written informed consent. The treatment regimen consisted of 3 courses of single-agent S-1 or S-1/cisplatin combination followed by weekly paclitaxel (wPTX). The endpoints of the study were entry to the second-line treatment, time to failure (TTF), and MST. Results: Of 39 patients enrolled, 37 completed first- line S-1. Twenty-eight patients (76%) then received wPTX, 2 non-wPTX chemotherapy, and 6 surgery; only 1 received no additional treatments. Second-line wPTX was followed by a third-line treatment in 23/28 patients (82%). The TTF with the sequential fixed regimen was 7 months. The MST and the 1- and 2-year survival rates in the 37 completing first-line treatment were 14.6 months, 61% and 25%, while those in the 28 switched over to wPTX were 12.5 months, 51% and 17%. Conclusions: Patients with advanced/recurrent gastric cancer treated sequentially with a fixed number of courses of S-1 followed by wPTX may have a good chance of treatment continuation. A sequential fixed regimen may further improve survival of patients with advanced/recurrent gastric cancer only with combinations of currently available drugs. No significant financial relationships to disclose.

A phase II trial of pemetrexed (P) in patients (pts) with performance status (PS) 2 and 3 as first- and second-line treatment for advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18149-18149 ◽  
Author(s):  
R. Zinner ◽  
F. V. Fossella ◽  
M. S. Kies ◽  
R. S. Herbst ◽  
C. Lu ◽  
...  
Keyword(s):  
Performance Status ◽  
Single Agent ◽  
Stage Iiib ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Minor Response ◽  
Men 2 ◽  
Line Of Therapy ◽  
Few Data

18149 P (Alimta) is approved as second-line therapy in pts with advanced NSCLC. In a phase III trial comparing P with docetaxel (D), median survival was 8.3 mos (P) vs 7.9 mos (D); P had a more favorable safety profile than D (Hanna, 2004). There are few data on pts with PS 3, and ASCO 2003 guidelines recommend that chemotherapy be reserved for pts with PS 0, 1 and possibly 2. Since P is well tolerated, PS3 pts may tolerate and benefit from it. In this trial, we treated 20 pts with stage IIIb/IV NSCLC and PS 2–3 who were chemo-naive or had received 1 prior regimen. Pts received P 500 mg/m2 IV D1 Q 3 wks. All pts received folic acid, vitamin B12 and dexamethasone prophylaxis. Serial blood samples were obtained to monitor inflammatory cytokines, and symptoms were monitored using the validated MDASI instrument. All pts were assessable for toxicity-symptoms, and 17 pts were evaluable for response (assessed after first cycle). Pt characteristics: 8 pts were PS 3 (4/8 first line) and 12 pts were PS 2 (6/12 first line). Median age was 69 for PS3 and 68 for PS2. 5/8 PS3 pts and 6/12 PS2 pts were men. 2/8 PS3 pts and 4/12 PS2 pts had stage IIIb. 4/8 PS3 pts and 6/12 PS2 pts were chemo-naive. Grade 3–4 toxicities for PS3/PS2 cohorts were: neutropenia 0/1 pt, anemia 1/2, fatigue 2/0, pneumonia 1/1, hypotension 1/1, neutropenic fever 0/1, atrial fibrillation 1/1. Response rates (RR) in PS3 pts were minor response (MR) 1/8, stable disease (SD) 5/8, progressive disease (PD) 2/8; RR in PS2 pts were partial response (PR) 1/12, MR 2/12, SD 3/12, PD 3/12, inevaluable 3/12. RR by line of therapy: first-line 6/10 SD, 2/10 PD, 2/10 inevaluable, and second-line, 1/10 PR, 2/10 MR, 3/10 SD, 3/10 PD, and 1/10 inevaluable. Reasons for PS3 pts coming off study were progression (4/8), constitutional toxicity (3/8), fatal pulmonary emboli (1/8); PS2 pts came off study due to progression (5/12), constitutional toxicity (2/12), and pneumonia (1/12). 4/12 PS2 pts are still on study. These preliminary data suggest that single-agent P is well-tolerated and has a promising RR in poor PS pts. Total planned accrual is 30 PS3 and 45 PS2 pts. Survival, symptom, cytokine data will be presented. [Table: see text]

Frequency of cisplatin administration in patients presenting with advanced urothelial carcinoma in the community.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 285-285 ◽  
Author(s):  
Guru Sonpavde ◽  
Deidre Watson ◽  
Marcia Tourtellott ◽  
Erica Higgins ◽  
Charles Lance Cowey ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Performance Status ◽  
Single Agent ◽  
Unmet Need ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Cancer Centers ◽  
Ajcc Stage ◽  
Stage 4 ◽  
Advanced Urothelial Carcinoma

285 Background: Renal dysfunction, poor performance status, advanced age, and comorbidities may preclude standard frontline cisplatin-based chemotherapy in patients with advanced urothelial carcinoma (UC). We hypothesized that cisplatin-based regimens are not administered to the majority of patients in the community. A study was conducted to identify chemotherapy regimens administered by medical oncologists in community-based cancer centers. Methods: A retrospective study was conducted on patients with AJCC stage 4 UC presenting from 2001 to 2010 to Texas Oncology Cancer Centers. The frontline chemotherapy regimen was classified as cisplatin-based, carboplatin-based, non-platinum based and no chemotherapy administered. The association of age with administration of cisplatin was studied. Results: A total of 298 patients with stage 4 disease were eligible for this analysis out of 3574 patients with UC in this database. Of the 298 patients, 197 (66.1%) were male, the median age was 70 years (range 28-97), and the primary sites of disease were bladder (243, 81.5%), renal pelvis (41, 13.8%) and ureter (14, 4.7%). The regimens administered were cisplatin-based in 107 patients (35.9%), carboplatin-based in 81 (27.2%), non-platinum in 25 (8.4%), no chemotherapy was administered in 71 (23.8%) and data were not available in 14 patients (4.7%). Cisplatin administration appeared more common in patients aged ≤70 years (62 of 150, 41.3%) as opposed to >70 years (45 of 148, 30.4%), p=0.05. Non-cisplatin regimens or no chemotherapy were trending to be more commonly administered to patients >70 years (64.2 vs. 54.7%, p=0.10). Limitations of a retrospective database study apply and the reasons for not administering cisplatin are unclear. Conclusions: Cisplatin-based chemotherapy was administered to 35.9% of patients presenting with AJCC stage 4 UC to community cancer centers. Given that the majority of patients may not be cisplatin-eligible or candidates for chemotherapy, this population has a significant unmet need. Drug development focused on single agent therapy with tolerable, convenient and efficacious agents or combination regimens without a cisplatin backbone should be a priority.

Gemcitabine in combination with oxaliplatin as second-line therapy of advanced and metastatic NSCLC

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18157-18157
Author(s):  
A. J. Alencar ◽  
M. Blaya ◽  
L. Raez ◽  
N. Farfan ◽  
G. Lopes ◽  
...  
Keyword(s):  
Organ Failure ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Multi Organ Failure

18157 Background: Single agent gemcitabine is active as second line therapy in NSCLC. Oxaliplatin may be non-cross resistant with the other platinum-containing agents used as first-line therapy in NSCLC. The combination of gemcitabine and oxaliplatin (GEMOX) is synergistic in pre-clinical models. Methods: A phase II, non-randomized trial was designed to assess the efficacy and tolerability of gemcitabine 1,000 mg/m2 over 100 min in combination with oxaliplatin 100 mg/m2 over 2 hours both given on days 1 and 15 of each 28-day cycle. Patients with NSCLC were eligible if they had progressed after first line treatment. Primary endpoint was tumor response rate. Planned sample size is 30 patients over a period of 2 years. Functional Assessment of Cancer Therapy- Lung (FACT-L) v.4 questionaire was used to assess quality of life of patients on therapy. Results: Twenty-two patients have been enrolled. 13 males (59%) and 9 females (41%). 15 Hispanic (68%), 4 Caucasian (18%), and 3 African-American (13%). Median age is 55 yrs. Histologic subtypes are as follows: adenocarcinoma, 12; NSCLC not otherwise specified 7; squamous cell carcinoma, 3. Nine patients had an ECOG performance status (PS) of 0 (41%) and 13 had a PS of 1 (59%). Two patients were never smokers. A total of 56 cycles have been administered (median 2, range 1 to 6). GEMOX as second-line therapy was given to 18 patients (81%), third-line to 4 patients (18%). Two patients died on study from disease progression leading to respiratory and multi-organ failure. The following Grade 3 and 4 adverse events were seen in 2 patients each: fatigue, dyspnea, anemia, and multi-organ failure. Cancer pain was seen in 1 patient. Twenty patients are available for assessment of response. Two patients had a confirmed partial response (10%) and another eight had stable disease (40%). Preliminary results of FACT-L analysis in 19 pts shows improvement in Lung Cancer Subscale (LCS) score in 25% of the patients after 2 cycles of therapy. Conclusions: Combination gemcitabine and oxaliplatin is active and well tolerated as second line treatment for NSCLC. Improvement of LCS score after 2 cycles suggests a clinical benefit that is beyond the observed response rate of 10%. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document