Nomogram to estimate the activity of second-line therapy for advanced urothelial carcinoma (UC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4524-4524
Author(s):  
Guru Sonpavde ◽  
Gregory Russell Pond ◽  
Neeraj Agarwal ◽  
Toni K. Choueiri ◽  
Angela Q. Qu ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Phase Ii ◽  
Performance Status ◽  
Phase Iii ◽  
Second Line ◽  
Phase Ii Trials ◽  
Second Line Therapy ◽  
Ecog Performance Status ◽  
Line Therapy ◽  
The Impact

4524 Background: Prognostic factors may impact on endpoints used in phase II trials of second-line therapy for advanced UC. We aimed to study the impact of prognostic factors (liver metastasis [LM], anemia [Hb<10 g/dl], ECOG-performance status [PS] ≥1, time from prior chemotherapy [TFPC]) on PFS6 and RR. Methods: Twelve phase II trials evaluating second-line chemotherapy and/or biologics (n=748) in patients with progressive disease were pooled. PFS was defined as tumor progression or death from any cause. PFS6 was defined from the date of registration and calculated using the Kaplan-Meier method. RR was defined using RECIST 1.0. A nomogram predicting PFS6 was constructed using the RMS package in R (www.r-project.org). Results: Data regarding progression, Hb, LM, PS and TFPC were available from 570 patients. The mean age was 65.1 years, 45.3% had ECOG-PS ≥1, 30.2% had LM, 14.6% had anemia and TFPC was <6 months (mo) in 60.2%. The overall median PFS was 2.7 mo, PFS6 was 22.2% (95% CI: 18.8-25.9) and RR was 17.5% (95% CI: 14.5%-20.9%). For every unit increase in risk group, the hazard of progression increased by 41% and the odds of response decreased by 48% (Table). A nomogram was constructed to predict PFS6 on an individual patient level. Conclusions: PFS6 and RR vary as a function of prognostic factors in patients receiving second-line therapy for advanced UC. A nomogram incorporating prognostic factors might facilitate the evaluation of activity across phase II trials enrolling heterogeneous populations and can help to select and stratify patients for phase III evaluation of suitable agents. [Table: see text]

Impact of baseline prognostic factors on progression-free survival at 6 months (PFS6) and response in patients receiving second-line therapy for advanced urothelial carcinoma (UC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 301-301 ◽  
Author(s):  
Gregory Russell Pond ◽  
Neeraj Agarwal ◽  
Joaquim Bellmunt ◽  
Toni K. Choueiri ◽  
Angela Q. Qu ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Phase Ii ◽  
Risk Group ◽  
Performance Status ◽  
Second Line ◽  
Phase Ii Trials ◽  
Second Line Therapy ◽  
Ecog Performance Status ◽  
Line Therapy ◽  
The Impact

301 Background: PFS6 was identified to be a robust intermediate endpoint in the setting of second-line therapy for advanced UC (Sonpavde, ESMO Congress, 2012) We studied the impact of second-line prognostic factors (Sonpavde, ESMO Congress 2012) (liver metastasis [LM], anemia [Hb<10 g/dl], ECOG-performance status [PS] ≥1, time from prior chemotherapy [TFPC]) on PFS6 and response rate (RR) to enable comparison of outcomes across phase II trials. Methods: Twelve phase II trials evaluating second-line chemotherapy and/or biologics (n=748) in patients with progressive disease were pooled. PFS was defined as tumor progression or death from any cause. PFS6 was defined from the date of registration and calculated using the Kaplan-Meier method. Results: Data regarding progression, Hb, LM, PS and TFPC were available in 570 patients, who were considered evaluable. The mean age was 65.1 years, 45.3% had ECOG-PS ≥1, 30.2% had LM, 14.6% had anemia and TFPC was <6 months (mo) in 60.2%. The overall median PFS was 2.7 mo, PFS6 was 22.2% (95% CI: 18.8-25.9) and RR was 17.5% (95% CI: 14.5%-20.9%). PFS6 and RR varied significantly according to risk group (Table). For every unit increase in risk group, the hazard of progression in 6 mo increased by 41% and the odds of response decreased by 48%. Conclusions: PFS6 and RR vary as a function of prognostic factors in patients receiving second-line therapy for advanced UC. These data facilitate comparison of outcomes across phase II trials enrolling heterogeneous populations. [Table: see text]

Time from prior chemotherapy (TFPC) as a prognostic factor in advanced urothelial carcinoma (UC) receiving second-line systemic therapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4522-4522
Author(s):  
Gregory Russell Pond ◽  
Guru Sonpavde ◽  
Toni K. Choueiri ◽  
Angela Q. Qu ◽  
David J. Vaughn ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Metastatic Disease ◽  
Performance Status ◽  
Cox Proportional Hazards ◽  
Prognostic Impact ◽  
Second Line ◽  
Phase Ii Trials ◽  
Second Line Therapy ◽  
Prior Chemotherapy ◽  
Line Therapy

4522 Background: Prognostic factors for overall survival (OS) in patients receiving second-line chemotherapy for advanced platinum-pretreated UC include ECOG performance status (PS) >0, hemoglobin (Hb) <10g/dL and the presence of liver metastasis (LM) (Bellmunt J, J Clin Oncol 2010). We hypothesized that time from prior chemotherapy (TFPC) independently impacts OS. Methods: Of 11 available phase II trials evaluating second-line therapy for advanced UC (n=698), 6 trials with available baseline Hb, PS and LM were utilized (n=534). The trials evaluated vinflunine (2 trials), docetaxel plus vandetanib or placebo, paclitaxel-gemcitabine, nanoparticle-albumin-bound paclitaxel and paclitaxel-cetuximab. The Kaplan-Meier method was used to estimate OS from date of starting second-line therapy. Cox proportional hazards regression stratified for trial was used to evaluate the prognostic effect of factors on OS. TFPC was evaluated as a continuous variable, and based on cutpoints of 3, 6, 9 and 12 months (mo) from prior chemotherapy to first study treatment. The choice of optimal cutpoint for TFPC was determined by the maximum likelihood ratio χ2 statistic. Results: Overall, 513 patients were evaluable. 64.1% received prior chemotherapy for metastatic disease. Median OS was 6.8 mo (95% CI: 6.1 to 7.4); range was 0 to 84.2 mo. Median OS was 5.2, 7.1, 8.8, 7.6 and 10.6 mo respectively for TFPC <3 (n=181), 3 to <6 (n=133), 6 to <9 (n=77), 9 to <12 (n=45) and >12 (n=77) mo, respectively. Shorter TFPC was independently prognostic for decreased survival. The optimal cutpoint for TFPC was <3 mo, but no well-defined plateau was observed. PS>0 (HR=1.72, p<0.001), LM (HR=1.41, p=0.002), Hb <10 g/dl (HR=1.59, p=0.001) and TFPC <3 mo (HR=1.67, p<0.001) were significantly prognostic in the multivariate model. Timing of prior chemotherapy (metastatic disease vs. perioperative) was not prognostic. Conclusions: A shorter duration of TFPC exhibited a significant negative prognostic impact on OS independent of known prognostic factors in patients receiving second-line therapy for advanced UC. If externally validated, TFPC should be a stratification factor in trials of second-line therapy for advanced UC.

Impact of response to prior chemotherapy (RTPC) on outcomes in second-line therapy for advanced urothelial carcinoma (UC): Implications for trial design.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4539-4539
Author(s):  
Gregory Russell Pond ◽  
Joaquim Bellmunt ◽  
Ronan Fougeray ◽  
Toni K. Choueiri ◽  
Angela Q. Qu ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Multivariable Analysis ◽  
Prognostic Impact ◽  
Second Line ◽  
Phase Ii Trials ◽  
Second Line Therapy ◽  
Prior Chemotherapy ◽  
Prior Therapy ◽  
Line Therapy ◽  
The Impact

4539 Background: Performance status (PS), hemoglobin (Hb), liver metastasis (LM), and time from prior chemotherapy (TFPC) are significant prognostic factors in second-line therapy for advanced UC. Setting of prior chemotherapy, i.e., metastatic or perioperative, has not appeared significant. However, the impact of prior chemosensitivity is unclear, which may confound trial interpretation. Hence, we examined the prognostic impact of RTPC, when prior therapy was given for metastatic disease. Methods: Six phase II trials evaluating second-line chemotherapy and/or biologics (n=504) were pooled. Patients who received prior therapy for metastatic disease were eligible for analysis if data regarding Hb, LM, PS, and TFPC were available. Response by RECIST to first-line therapy was recorded. Progression-Free Survival (PFS) and overall survival (OS) were calculated from the date of registration using the Kaplan-Meier method. Results: 275 pts were evaluable for analysis. Patients received gemcitabine-paclitaxel, cyclophosphamide-paclitaxel, pazopanib, docetaxel plus vandetanib/placebo or vinflunine (2 trials). Those with prior response (n=111) had a median (95% CI) OS of 8.0 (6.8-9.4) months (mo) and PFS of 3.0 (2.6-4.0), compared with OS and PFS of 5.9 (5.0-6.6) mo and 2.6 (2.0-2.8) for those without prior response (n=164). Multivariable analysis did not reveal an independent impact of RTPC on PFS or OS (Table). Conclusions: RTPC in patients receiving prior chemotherapy for metastatic disease did not confer an independent prognostic impact with second-line therapy for advanced UC. Patients who received prior chemotherapy in peri-operative or metastatic settings may be enrolled in the same second-line trial stratified for PS, anemia, LM and TFPC. [Table: see text]

Sunitinib therapy for patients (pts) with metastatic renal cell carcinoma (mRCC): Updated results of two phase II trials and prognostic factor analysis for survival

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5095-5095 ◽  
Author(s):  
J. E. Rosenberg ◽  
R. J. Motzer ◽  
M. D. Michaelson ◽  
B. G. Redman ◽  
G. R. Hudes ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Treatment Plan ◽  
Objective Response ◽  
Time Interval ◽  
Second Line ◽  
Phase Ii Trials ◽  
First Line ◽  
Second Line Therapy ◽  
Eligibility Criteria ◽  
Line Therapy

5095 Background: Two single-arm phase 2 trials reported a 42% objective response rate (ORR) with sunitinib as second-line therapy in mRCC pts (JAMA 2006;295:2516–24). Efficacy results were updated and an analysis of prognostic factors for survival was performed on pooled data. Methods: Eligibility criteria and treatment plan were nearly identical for both trials. Pts with mRCC who failed =1 prior cytokine-based therapy received sunitinib in repeated 6-week cycles of 50 mg/day orally for 4 weeks, followed by 2 weeks off treatment. Response was assessed by investigators according to RECIST. Pretreatment clinical and biochemical features were examined for prognostic factors by univariate and multivariate analysis (p<0.05 significance level was used in the backward stepwise selection procedure). Results: Updated efficacy data for 168 evaluable pts showed an ORR of 45% (95% CI: 39%, 54%), median progression-free survival (PFS) of 8.4 months (95% CI: 7.9, 10.7), and median overall survival (OS) of 22.3 months (95% CI: 14.8, 36.0). Twenty pts remain on treatment with sunitinib with the longest pt on the drug for >3.5 years with partial response for >3 years. The median duration of response was 11.6 months (95% CI: 9.9, 15.2), and included 1 pt with a complete response for >2 years. The proportion of pts alive at 2 years is 48%. Final prognostic factors for survival in the multivariate model were ECOG PS 0 vs. =1 (p=0.0034); time interval from diagnosis to sunitinib treatment =1 yr vs. <1 yr (p=0.0002); hemoglobin =13 vs. <13 g/dL for males and =11.5 vs. <11.5 g/dL for females (p=0.0002). Conclusions: Median survival is nearly 2 years, which compares favorably to the historical experience (12.7 months) in second-line therapy with other agents (JCO 2004;22:454–63). The influence of sunitinib therapy on patient survival is being investigated in a randomized phase 3 trial compared to interferon-a in first-line therapy for mRCC. Further study of prognostic factors to sunitinib therapy is warranted in the first-line setting. No significant financial relationships to disclose.

Dovitinib as second-line therapy in patients with fibroblast growth factor receptor 2 (FGFR2)-mutated or non-mutated advanced and/or metastatic endometrial cancer (EC): A single-arm, multicenter, phase II study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS5616-TPS5616
Author(s):  
Gottfried E. Konecny ◽  
Neil Finkler ◽  
Agustin Garcia ◽  
Francesco Raspagliesi ◽  
Carolina Muriel Lopez ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Second Line ◽  
Open Label ◽  
Second Line Therapy ◽  
Line Therapy

TPS5616 Background: Despite the use of combination chemotherapy and introduction of novel targeted agents, the prognosis for advanced and/or metastatic EC is challenging. The occurrence of somatic activating FGFR2 mutations in EC suggests an opportunity for testing FGFR inhibitors. Dovitnib (DOV) is a potent receptor tyrosine kinase inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor and FGFR. The objective of the study is to investigate the efficacy and safety of DOV as second-line therapy in patients (pts) with advanced and/or metastatic EC. Methods: This multicenter, non-randomized, open label, single-arm, phase II study (NCT01379534) will enroll adult female pts (N~80) with either FGFR2 mutated (group 1) or non-mutated (group 2) histologically confirmed advanced and/or metastatic EC, who have documented radiological evidence of progressive disease (RECISTv1.1) after 1 prior line of chemotherapy, excluding adjuvant therapy. Eligible pts also need to have ≥1 measurable lesion (RECISTv1.1) and ECOG performance status ≤ 2. Pts will receive oral DOV of 500 mg/day, on a 5-days-on / 2-days-off dosing schedule until disease progression, unacceptable toxicity, death, or discontinuation due to any other reason. Primary endpoint is 18-week progression-free survival (PFS) rate (local review; RECIST v1.1) and secondary endpoints include overall response rate, disease control rate, duration of response, PFS, overall survival, safety, tolerability, pharmacokinetics, and pharmacodynamic effect of DOV on soluble plasma biomarker expression level. A 2-stage design with Bayesian interim monitoring (interim for futility analyses) will be used in each group. For stage 1, 20 pts will be enrolled into each group. If ≥ 8 of the first 20 pts with measurable disease at baseline in either group are progression-free after 18 weeks of treatment, 20 additional pts will be enrolled into that group in stage 2. Preliminary results for each group will be evaluated in the interim analysis. As of 20 January 2013, 43 pts have been enrolled (12 with and 31 without FGFR2 mutations). Clinical trial information: NCT01379534.

Nomogram to assess benefit of new over historical agents as salvage therapy for metastatic urothelial carcinoma (mUC) in non-randomized trials: Effect of atezolizumab on 12-month survival.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 346-346 ◽  
Author(s):  
Gregory Russell Pond ◽  
Guru Sonpavde ◽  
Jonathan E. Rosenberg ◽  
Toni K. Choueiri ◽  
Joaquim Bellmunt ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Phase Ii ◽  
Salvage Therapy ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Phase Ii Trials ◽  
Phase Ii Studies ◽  
The Impact

346 Background: Early surrogate endpoints of benefit in mUC phase 2 salvage therapy trials are necessary to identify promising drugs, particularly for checkpoint inhibitors where response and progression-free survival are inadequate. We developed a nomogram using prognostic variables from phase 2 trials of historical agents to estimate 12 month survival to which observed survival in single arm trials could be compared. Methods: Data were obtained from phase II trials of salvage therapy for mUC for survival and 5 prognostic factors: hemoglobin, performance status, liver metastasis, treatment-free interval and albumin. Patients (pts) were randomly allotted to discovery:validation (DIS:VAL) datasets in a 2:1 ratio. A nomogram was developed for estimating 12-month survival. Calibration plots were constructed in the VAL dataset by plotting estimated vs. observed 12-mo survival and data bootstrapped to assess performance. The nomogram was applied to external nonrandomized salvage therapy data: 1) retrospective pemetrexed data or 2) trials of atezolizumab: PCD4989g and IMvigor210. Results: Data were available from 340 pts receiving sunitinib (n = 77), everolimus (n = 45), docetaxel + vandetanib or placebo (n = 109), pazopanib (n = 42), paclitaxel (n = 36) and docetaxel (n = 31). Calibration and prognostic ability of the model was acceptable (c-index = 0.634, 95% CI = 0.596-0.652). Observed 12-month survival for pts on pemetrexed (n = 127, 23.5% [95% CI: 16.2%-31.7%]) were similar to nomogram-predicted survival (19% [95% CI: 16.5-21.5], P> 0.05), while observed result with atezolizumab (n = 403, 39.0% [95% CI: 34.1-43.9]) exceeded predicted result (24.6% [95% CI: 23.4-25.8], P< 0.001). Conclusions: Atezolizumab was associated with a significantly longer 12-mo survival compared to nomogram-predicted survival while pemetrexed was not. This nomogram incorporates baseline prognostic factors to provide expected 12-mo survival of phase 2 patient cohorts with which to compare observed survival, thereby providing a useful tool to quantify benefit in phase II studies while controlling for the impact of clinical variables.

Correlation of progression-free survival at 6 months (PFS6) with overall survival at 12 months (OS12) in an analysis of 10 trials of second-line therapy for advanced urothelial carcinoma (UC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4525-4525 ◽  
Author(s):  
Benjamin Maughan ◽  
Kenneth M. Boucher ◽  
Neeraj Agarwal ◽  
Toni K. Choueiri ◽  
Angela Q. Qu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Survival Data ◽  
Pearson Correlation ◽  
Second Line ◽  
Phase Ii Trials ◽  
Second Line Therapy ◽  
Individual Level ◽  
Line Therapy ◽  
The Individual ◽  
The Relationship

4525 Background: Second-line therapy of advanced UC is a significant unmet need. While phase II trials have relied on response rate (RR) as a primary endpoint, response may not be suitable for assessing cytostatic agents and does not capture duration of benefit. We hypothesized that PFS6 correlates with OS12 and may be a robust intermediate endpoint for phase II trials. Methods: Ten trials with individual patient progression and survival data (n=646) evaluating chemotherapy and/or biologics following chemotherapy were combined. Progression was defined as tumor progression (RECIST 1.0 in 9 trials, WHO in 1 trial), or death from any cause. Unadjusted and adjusted binomial confidence intervals for PFS6, OS12 and response were reported, with adjustment for variability between trials using random effects models. The relationship between PFS6 and OS12 was assessed at the trial level using Pearson correlation and weighted linear regression with larger studies having more influence. The relationship between PFS6 and OS12 at the individual level was assessed using Pearson chi-square test with Yates continuity correction. Statistical analyses employed “R” statistical computing software, version 2.8.0. Results: 59% had visceral metastasis and performance status was 0, 1 and 2 in 50, 39 and 8%, respectively. Median age was 65 years (31-88) and 77% were male. PFS6 was 22% (95% CI: 17-24%), and adjusted PFS6 was 23% (95% CI: 15-34%). The OS12 was 20% (95% CI: 17-24%), and adjusted OS12 was 21% (95% CI: 15-29%). The Pearson correlation between trial level PFS6 and OS12 was 0.66 (p = 0.037). The individual level agreement between PFS6 and OS12 was seen in 82% of patients (kappa = 0.45). Among 560 patients evaluable for response and OS, the RR was 22% (95% CI: 18-25%) and adjusted RR was 21% (95% CI: 13-32%). Trial level Pearson correlation between response and OS12 was 0.37 (p = 0.30), and individual level agreement was seen in 78% (kappa=0.36). Conclusions: PFS6 is associated with OS12 at the trial and individual levels in patients receiving second-line therapy for advanced UC. The association of response with OS was suboptimal. Validation of PFS6 is warranted.

A phase II study of second-line S-1/CPT-11+bev for advanced colon cancer (NCCSG04): Subset analysis by K-ras, EGFR, UGT1A1, and previous bevacizumab.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 564-564
Author(s):  
Yasumasa Takii ◽  
Kouichi Furukawa ◽  
Satoshi Maruyama ◽  
Toshiyuki Yamazaki ◽  
Atsushi Nishimura ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Ecog Performance Status ◽  
Line Therapy ◽  
Negative Case ◽  
Wild Group

564 Background: We planned a phase II trial to evaluate the efficacy and safety of irinotecan, S-1, and bevacizumab (IRIS/Bev) as second-line therapy for patients with metastatic colorectal cancer (mCRC). The result of this study was reported an active and generally well-tolerated 2nd-line treatment for mCRC (Takii et al. ASCO-GI 2013 #496). We analyzed subset of EGFR, K-ras, UGT1A1, and previous Bev. Methods: The study design was multicenter, single-arm, open-label phase II study. Eligible patients had to have mCRC with confirmed diagnosis of adenocarcinoma, history of oxaliplatin containing regimen as first-line therapy, an age from 20 to 80 years, ECOG performance status (PS) of 0-1. S-1 65 mg/m2 daily p.o. was given on days 1-14 and Irinotecan 75mg/m2and bevacizumab 10mg/kg i.v. were given on days 1 and 15 of a 28-day cycle. We retrospectively examined progression-free survival (PFS), overall response rate (OR), overall survival (OS), time to treatment failure (TTF) and safety by K-ras, EGFR, UGT1A1, and previous Bev status. Results: Thirty-four patients were investigated. The OR was 21.1% (7/33) and disease control rate was 84.8% (28/33). Median PFS was 8.9 months, median TTF was 8.2 months and median OS was 23.4 months. Median PFS was 9.9 months on K-ras wild group and 6.6 months on K-ras mutant group (p = 0.517). Median OS was not reached on K-ras wild group and 16.4 months on K-ras mutant group (p = 0.097). The EGFR-negative case was three cases, and it did not become a data to compare because of small number. Median PFS was 8.5 months on previous Bev group and 9.9 months on previous no-Bev group (p = 0.637). Median OS was not reached on previous Bev group and 23.1 months on previous no-Bev group (p = 0.701). Median PFS, TTF and OS was no different between UGT1A1 wild group and mutant group. On safety analysis, there were no different between the two groups, respectively. Conclusions: IRIS/Bev is an active and well-tolerated second-line treatment for patients with mCRC. Only K-ras status influendced OS. Clinical trial information: UMIN000001631.

scholarly journals Benefit of second-line therapy for advanced esophageal squamous cell carcinoma: a tri-center propensity score analysis

2021 ◽  
Vol 13 ◽  
pp. 175883592110399
Author(s):  
Moritz Müller ◽  
Florian Posch ◽  
Dominik Kiem ◽  
Dominik Barth ◽  
Lena Horvath ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Propensity Score ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Performance Status ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Ecog Performance Status ◽  
Line Therapy

Background: The level of evidence for palliative second-line therapy in advanced esophageal squamous cell carcinoma (aESCC) is limited. This is the first study that reports efficacy data comparing second-line therapy + active symptom control (ASC) versus ASC alone in aESCC. Methods: We conducted a tri-center retrospective cohort study ( n = 166) including patients with aESCC who had experienced disease progression on palliative first-line therapy. A propensity score model using inverse probability of treatment weighting (IPTW) was implemented for comparative efficacy analysis of overall survival (OS) in patients with second-line + ASC ( n = 92, 55%) versus ASC alone ( n = 74, 45%). Results: The most frequent second-line regimens used were docetaxel (36%) and paclitaxel (18%). In unadjusted primary endpoint analysis, second-line + ASC was associated with significantly longer OS compared with ASC alone [hazard ratio (HR) = 0.49, 95% confidence interval (CI): 0.35–0.69, p < 0.0001]. However, patients in the second-line + ASC group were characterized by more favorable baseline features including a better Eastern Cooperative Oncology Group (ECOG) performance status, a longer first-line treatment duration and lower C-reactive protein levels. After rigorous adjusting for baseline confounders by re-weighting the data with the IPTW the favorable association between second-line and longer OS weakened but prevailed. The median OS was 6.1 months in the second-line + ASC group and 3.2 months in the ASC group, respectively (IPTW-adjusted HR = 0.40, 95% CI: 0.24–0.69, p = 0.001). Importantly, the benefit of second-line was consistent across several clinical subgroups, including patients with ECOG performance status ⩾1 and age ⩾65 years. The most common grade 3 or 4 adverse events associated with palliative second-line therapy were hematological toxicities. Conclusion: This real-world study supports the concept that systemic second-line therapy prolongs survival in patients with aESCC.

Sign in / Sign up

Export Citation Format

Share Document