Analysis of early tumor shrinkage and depth of response in patients with advanced biliary tract cancer treated with gemcitabine plus cisplatin or gemcitabine plus S-1: An exploratory analysis of JCOG1113.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 301-301
Author(s):  
Naohiro Okano ◽  
Chigusa Morizane ◽  
Takuji Okusaka ◽  
Ryo Sadachi ◽  
Tomoko Kataoka ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Tumor Shrinkage ◽  
High Group ◽  
Tract Cancer ◽  
Depth Of Response ◽  
Early Tumor Shrinkage ◽  
Multivariable Analyses ◽  
Early Tumor ◽  
The Impact

301 Background: JCOG1113 is a randomized phase III trial to confirm the non-inferiority of gemcitabine (GEM) plus S-1 (GS) compared with GEM plus cisplatin (GC) regarding overall survival (OS) in patients with advanced biliary tract cancer (BTC). Although the non-inferiority of GS to GC was demonstrated, the difference in the nature of tumor shrinkage effects between GC and GS is not clear. Early tumor shrinkage (ETS) and depth of response (DpR) are considered as on-treatment markers that reflect the anti-tumor effect to chemotherapy and have been reported to be associated with survival in metastatic colorectal cancer. However, there are few studies assessing ETS or DpR in advanced BTC. Therefore, we evaluated the association between ETS, DpR, and clinical outcomes in JCOG1113. Methods: We conducted an exploratory analysis of JCOG1113, which included chemotherapy-naïve patients with recurrent or unresectable BTC. ETS was defined as tumor reduction in the sum of the longest diameters of the target lesions at week 6 when compared with that at baseline. DpR was defined as the maximum tumor shrinkage observed until 12 weeks from enrollment. Survival curves were estimated using the Kaplan–Meier method. Progression-free survival (PFS) and OS for ETS and DpR were estimated from week 6 and 12 (landmarks) after enrollment, respectively. Multivariable analyses for PFS and OS, adjusted for baseline factors, were performed using a stratified Cox regression model. Results: Of the 354 registered patients in JCOG1113, 277 patients in the ETS group and 230 patients in the DpR group were included in this study. Seventy-seven patients (27.8%) achieved ETS ≥ 20% (ETS high group) and 52 patients (22.6%) achieved DpR ≥ 40% (DpR high group). The proportion of ETS high group (GC, 25.4%; GS, 30.4%) and DpR high group (GC, 21.2%; GS, 24.1%) was similar between the arms. The patient characteristics of ETS high group were not different between GC and GS. The hazard ratio (HR) of the ETS high group compared with the ETS low group for PFS and OS was 0.76 (95% confidence interval [CI] 0.58–1.00) and 0.80 (95% CI 0.60–1.07), respectively. The impact of ETS was higher in GC (HR 0.64, 95% CI 0.43–0.95) than GS (HR 0.88, 95% CI 0.60–1.28) in PFS. The HR of DpR high group compared with DpR low group for PFS and OS was 0.75 (95% CI 0.55–1.03) and 0.79 (95% CI 0.57–1.09), respectively. The impact of DpR was higher in GC (HR 0.63, 95% CI 0.40–0.998) than GS (HR 0.88, 95% CI 0.57–1.37) in PFS. ETS and DpR were significantly associated with both PFS and OS in the multivariable analyses. Conclusions: ETS and DpR may be useful as on-treatment markers associated with PFS and OS in patients with advanced BTC, especially in those treated with GC. Clinical trial information: UMIN000010667.

scholarly journals Early Tumor Shrinkage and Depth of Response Evaluation in Metastatic Pancreatic Cancer Treated with First Line Chemotherapy: An Observational Retrospective Cohort Study

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 939 ◽  
Author(s):  
Caterina Vivaldi ◽  
Lorenzo Fornaro ◽  
Carla Cappelli ◽  
Irene Pecora ◽  
Silvia Catanese ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Tumor Shrinkage ◽  
First Line ◽  
Free Survival ◽  
Depth Of Response ◽  
Early Tumor Shrinkage ◽  
Early Tumor

Early tumor shrinkage (ETS) and depth of response (DoR) predict favorable outcomes in metastatic colorectal cancer. We aim to evaluate their prognostic role in metastatic pancreatic cancer (PC) patients treated with first-line modified-FOLFIRINOX (FOLFOXIRI) or Gemcitabine + Nab-paclitaxel (GemNab). Hence, 138 patients were tested for ETS, defined as a ≥20% reduction in the sum of target lesions’ longest diameters (SLD) after 6–8 weeks from baseline, and DoR, i.e., the maximum percentage shrinkage in the SLD from baseline. Association of ETS and DoR with progression-free survival (PFS) and overall survival (OS) was assessed. ETS was reached in 49 patients (39.5% in the FOLFOXIRI, 29.8% in the GemNab group; p = 0.280). In the overall population, ETS was significantly associated with better PFS (8.0 vs. 4.8 months, p < 0.001) and OS (13.2 vs. 9.7 months, p = 0.001). Median DoR was −27.5% (−29.4% with FOLFOXIRI and −21.4% with GemNab, p = 0.016): DoR was significantly associated with better PFS (9.0 vs. 6.7 months, p < 0.001) and OS (14.3 vs. 11.1 months, p = 0.031). Multivariate analysis confirmed both ETS and DoR are independently associated with PFS and OS. In conclusion, our study added evidence on the role of ETS and DoR in the prediction of outcome of PC patients treated with first-line combination chemotherapy.

Correlation between overall survival and other efficacy endpoints in advanced biliary tract cancer: Literature-based analysis from 13 randomized trials of first-line chemotherapy.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 352-352
Author(s):  
Toshikazu Moriwaki ◽  
Shinji Endo ◽  
Yoshiyuki Yamamoto ◽  
Takeshi Yamada ◽  
Akinori Sugaya ◽  
...  
Keyword(s):  
Overall Survival ◽  
Correlation Coefficient ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Randomized Trials ◽  
First Line ◽  
Biliary Tract Neoplasms ◽  
Tract Cancer ◽  
The Impact ◽  
Line Chemotherapy

352 Background: Chemotherapy for advanced biliary tract cancer (ABC) has progressed. Now gemcitabine plus cisplatin combination is considered the standard 1st-line treatment based on the results of many randomized studies. However, the impact of various efficacy parameters on overall survival (OS) remains unclear. Methods: We searched PubMed database with the key words of (“biliary tract neoplasms” or “bile duct neoplasms” or “gallbladder neoplasms” or “cholangiocarcinoma” [All fields]) AND (“chemotherapy”[All fields]) AND Clinical trial [ptyp] between Apr 1984 to Jun 2013 and abstracts presented at the meetings of ASCO/Gastrointestinal Cancers Symposium (2004–2013) and ESMO/WCGC (2002–2013). Then we identified randomized trials of 1st-line chemotherapy for ABC, and analyzed the relations between the results of OS and those of progression-free survival (PFS) or time to progression (TTP), response rate (RR), disease control rate (DCR), post-progression survival (PPS = median OS − median PFS/TTP), and the proportion of patients who received 2nd-line chemotherapy (%2nd). Results: Among 329 papers/abstracts retrieved, 13 randomized trials, 26 treatment arms of first-line chemotherapy for ABC were identified. Number of trials with information on median OS, median PFS/TTP, hazard ratio (HR) for OS and PFS/TTP, RR, DCR, and %2nd were 13, 13, 6, 13, 12, and 7, respectively. The analysis of all these trials demonstrated the median values (range) of OS, PFS/TTP, HR of OS, HR of PFS/TTP, RR, DCR, PPS, and %2nd were 9.4 (4.6–13) months, 5.3 (2.7–8.5) months, 0.71 (0.39–0.93), 0.65 (0.44–0.85), 20 (7.1–36) %, 67 (21–87) %, 4.0 (1.0–7.6) months, and 41 (15–79) %, respectively. Spearman rank correlation coefficient of differences (Δ) OS with ΔPFS/TTP, ΔRR, ΔDCR, and ΔPPS were 0.66, − 0.07, 0.66, and 0.34, respectively. The correlation coefficient between HRs for PFS/TTP and OS was 0.60. The correlation coefficient between ΔPPS and Δ%2nd was − 0.15. Conclusions: OS was moderately associated with PFS/TTP and DCR.

Right-sided colorectal cancer (RC): Response to first-line chemotherapy in FIRE-3 (AIO KRK-0306) with focus on early tumor shrinkage (ETS) and depth of response (DpR).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3586-3586 ◽  
Author(s):  
Julian Walter Holch ◽  
Sebastian Stintzing ◽  
Swantje Held ◽  
Ludwig Fischer von Weikersthal ◽  
Thomas Decker ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rank Test ◽  
Tumor Shrinkage ◽  
First Line ◽  
Depth Of Response ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Radiological Data ◽  
Early Tumor Shrinkage ◽  
Early Tumor

3586 Background: Recent evidence suggests that benefit from anti-EGFR treatment is restricted to RAS wild-type left-sided colorectal cancer (LC) (Holch JW et al. Eur J Cancer 2017). However, these results are preliminary. We therefore investigated patients with RC enrolled in the FIRE-3 trial, which evaluated the efficacy of first-line FOLFIRI plus either cetuximab (cet) or bevacizumab (bev) in RAS wildtype mCRC. New metrics of tumor dynamics were used to characterize the patients. Methods: The splenic flexure was used to differentiate LC from RC. Survival analysis was done using Kaplan-Meier estimation and differences were expressed using Log-Rank test, hazard ratios (HR) and corresponding 95% confidence intervals. Central independent radiological data was used to calculate early tumor shrinkage ≥20% (ETS) and depth of response (DpR). Results: In total, 330 patients were assessable for central radiological evaluation. In patients with LC (n = 257), treatment with FOLFIRI + cet led to longer overall survival (OS) compared to FOLFIRI + bev (HR = 0.68, p = 0.016). In patients with RC (n = 68), OS was comparable between treatment arms (HR = 1.11, p = 0.715). In patients with RC and ETS < 20%, OS was inferior in patients treated with FOLFIRI + cet. In patients who reached ETS ≥20%, a comparable OS was evident between treatment arms (for further details of efficacy in patients with RC see table). Conclusions: Patients with RC do not represent a uniform population. ETS ≥20% defines a subgroup of patients where comparable treatment efficacy was observed with regard to OS, ORR and DpR by addition of cetuximab vs. bevacizumab to FOLFIRI. [Table: see text]

The influence of renal function on gemcitabine-based chemotherapy for advanced biliary tract cancer: An exploratory subgroup analysis of JCOG1113.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 368-368
Author(s):  
Makoto Ueno ◽  
Chigusa Morizane ◽  
Takuji Okusaka ◽  
Gakuto Ogawa ◽  
Yuya Sato ◽  
...  
Keyword(s):  
Renal Function ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Tract Cancer ◽  
Grade 3 ◽  
The Impact

368 Background: JCOG1113 is a randomized phase III trial to evaluate gemcitabine (GEM) plus S-1 (GS) versus GEM plus cisplatin (GC) regarding overall survival (OS) for advanced biliary tract cancer (BTC) (UMIN000001685) and the non-inferiority of GS was demonstrated. It is necessary to consider renal function using cisplatin or S-1 because cisplatin has renal toxicity, and the toxicity of S-1 is affected by renal function. Therefore, we evaluated the influence of renal function on the efficacy and safety of GC and GS in JCOG1113. Methods: All enrolled patients (pts) in JCOG1113 (n = 354) were analyzed. Eligibility criteria included chemotherapy-naïve pts with recurrent or unresectable biliary tract adenocarcinoma, ECOG-PS of 0–1, CCr > 50 ml/min, and adequate organ function. Renal function was classified into two groups by creatinine clearance (CCr) as calculated by the Cockcroft-Gault formula; high CCr (CCr ≥ 80 ml/min) or low CCr (80 > CCr ≥ 50 ml/min). The impact of renal function on OS and progression-free survival (PFS) were compared using the Cox regression model. The adverse events (AEs) were compared using Fisher’s exact test. Results: Eighty-eight pts on GC and 88 pts on GS were included in the high CCr group, and 87 pts on GC and 91 pts on GS were included in the low CCr group. There were no differences between the groups regarding, sex, PS, primary site, biliary drainage, operation, or recurrence, except for age. The hazard ratio (HR) of GS to GC for OS was 1.12 (95% CI 0.81–1.56) in the high CCr group and 0.80 (95% CI 0.58–1.11) in the low CCr group. The HR of GS to GC for PFS was 1.06 (95% CI 0.78–1.44) in the high CCr group and 0.69 (95% CI 0.50–0.94) in the low CCr group. Grade 3-4 AEs of white blood cell count decreased (35.3%/23.6%), anemia (29.4%/7.9%) and platelet count decreased (18.8%/10.1%) were more common in GC than GS in the low CCr group. In contrast, the incidence of all grade 3-4 non-hematological AEs was higher (36.0%/11.8%) in GS than GC in the low CCr group ( p = 0.0002). Conclusions: GS was better in terms of OS, PFS, and hematological toxicities than GC in the low CCr group. GS might be recommended for the population with lower renal function in the treatment for advanced BTC.

Adjuvant Therapy in the Treatment of Biliary Tract Cancer: A Systematic Review and Meta-Analysis

2012 ◽  
Vol 30 (16) ◽  
pp. 1934-1940 ◽  
Author(s):  
Anne M. Horgan ◽  
Eitan Amir ◽  
Thomas Walter ◽  
Jennifer J. Knox
Keyword(s):  
Systematic Review ◽  
Adjuvant Therapy ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Meta Analysis ◽  
Random Effect ◽  
Published Data ◽  
Curative Intent ◽  
Tract Cancer ◽  
The Impact

PurposeThe benefit of adjuvant therapy (AT) for biliary tract cancer (BTC) is unclear, with conflicting results from nonrandomized studies. We report a systematic review and meta-analysis to determine the impact of AT on survival.MethodsStudies published between 1960 and November 2010, which evaluated adjuvant chemotherapy (CT), radiotherapy (RT), or both (CRT) compared with curative-intent surgery alone for resected BTC were included. Only tumors of the gallbladder and bile ducts were assessed. Published data were extracted and computed into odds ratios (ORs) for death at 5 years. Subgroup analyses of benefit based on lymph node (LN) or resection margin positivity (R1) were prespecified. Data were weighted by generic inverse variance and pooled using random-effect modeling.ResultsTwenty studies involving 6,712 patients were analyzed. There was a nonsignificant improvement in overall survival with any AT compared with surgery alone (pooled OR, 0.74; P = .06). There was no difference between gallbladder and bile duct tumors (P = .68). The association was significant when the two registry analyses were excluded. Those receiving CT or CRT derived statistically greater benefit than RT alone (OR, 0.39, 0.61, and 0.98, respectively; P = .02). The greatest benefit for AT was in those with LN-positive disease (OR, 0.49; P = .004) and R1 disease (OR, 0.36; P = .002).ConclusionThis analysis supports AT for BTC. Prospective randomized trials are needed to provide better rationale for this commonly used strategy. On the basis of our data, such trials could involve two active comparators rather than a no-treatment arm among patients with LN-positive or R1 disease.

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