scholarly journals Five-year follow-up of nivolumab treatment in Japanese patients with esophageal squamous-cell carcinoma (ATTRACTION-1/ONO-4538-07)

Esophagus ◽  
2021 ◽  
Author(s):  
Taroh Satoh ◽  
Ken Kato ◽  
Takashi Ura ◽  
Yasuo Hamamoto ◽  
Takashi Kojima ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Adverse Events ◽  
Esophageal Squamous Cell Carcinoma ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Japanese Patients

Abstract Background In the phase II ATTRACTION-1 study, nivolumab demonstrated a promising antitumor activity among Japanese patients with treatment-refractory advanced esophageal cancer. Here, we report the follow-up results of ATTRACTION-1 of > 5 years. Methods We enrolled patients with esophageal cancer that was refractory or intolerant to a standard chemotherapy. Then, nivolumab (3 mg/kg) was administered every 2 weeks. The primary endpoint was a centrally assessed objective response rate. Results Nivolumab was administered to 65 patients with esophageal squamous-cell carcinoma (ESCC). The centrally assessed objective response rate was 17.2%. The overall survival rates at 3 and 5 years were 10.9% and 6.3%, respectively. Three-year survivors tended to have more reduced target lesions. A total of 63.1% of the patients exhibited treatment-related adverse events, and no new safety signal was observed. Patients with select adverse events tended to have better overall survival than those without. No apparent chronological order was observed between the first response and the onset of select adverse events. Conclusion Our follow-up analysis of more than 5 years is currently the longest and is the first to demonstrate that nivolumab has long-term efficacy and safety for advanced ESCC.

scholarly journals Pembrolizumab Monotherapy for Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Arm Phase II Trial (KEYNOTE-629)

2020 ◽  
Vol 38 (25) ◽  
pp. 2916-2925 ◽  
Author(s):  
Jean-Jacques Grob ◽  
Rene Gonzalez ◽  
Nicole Basset-Seguin ◽  
Olga Vornicova ◽  
Jacob Schachter ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Free Survival ◽  
Duration Of Response

PURPOSE Treatment options are limited for patients with recurrent and/or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC); mortality rates exceed 70% in patients with distant metastases. Here, we present the first interim analysis of the R/M cSCC cohort from the 2-cohort—locally advanced and R/M—phase II KEYNOTE-629 study. PATIENTS AND METHODS Patients with R/M cSCC not amenable to surgery or radiation received pembrolizumab 200 mg every 3 weeks. The primary end point was objective response rate per RECIST v1.1. Secondary end points were duration of response, disease control rate, progression-free survival, overall survival, and safety. RESULTS At data cutoff (April 8, 2019), median follow-up of 105 enrolled patients in the R/M cohort was 11.4 months (range, 0.4 to 16.3 months). Objective response rate was 34.3% (95% CI, 25.3% to 44.2%; 4 complete responses, 32 partial responses), and disease control rate was 52.4% (95% CI, 42.4% to 62.2%). Median duration of response was not reached (range, 2.7 to 13.1+ months; ‘+’ refers to ongoing response at data cutoff). Median progression-free survival was 6.9 months (95% CI, 3.1 months to 8.5 months). Median overall survival was not reached (95% CI, 10.7 months to not reached). Treatment-related adverse events occurred in 66.7% of patients (n = 70), the most common of which were pruritus (n = 15; 14.3%), asthenia (n = 14; 13.3%), and fatigue (n = 13; 12.4%). Grade 3 to 5 treatment-related adverse events occurred in 5.7% (n = 6) of patients. One patient died of treatment-related cranial nerve neuropathy. CONCLUSION Pembrolizumab demonstrated effective antitumor activity; clinically meaningful, durable responses; and acceptable safety in primarily elderly patients with R/M cSCC, supporting its use in clinical practice. Pembrolizumab adverse events in this study were consistent with its established safety profile.

Results of a phase II study of capecitabine-based doublets in the treatment of metastatic triple-negative breast cancer (mTNBC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11538-e11538
Author(s):  
Ying Fan ◽  
Binghe Xu ◽  
Yuqian Liao ◽  
Fei Ma ◽  
Peng Yuan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cytotoxic Agents ◽  
Free Survival ◽  
Metastatic Setting ◽  
Secondary Endpoints

e11538 Background: It is extremely important to identify proper cytotoxic agents for TNBC which had limited choices except chemotherapy. Capecitabine are well established as a major chemotherapeutic agent in metastatic setting. The efficacy of capecitabine-based chemotherapy has not been prospectively studied in TNBC and data remains scant. This study was designed to investigate the efficacy of capecitabine-based doublets in the treatment of metastatic TNBC. Methods: Eligible metastatic TNBC women with measurable diseases were recruited to receive either TX regimen (docetaxel 75mg/m2 iv d1 plus capecitabine 1000mg/m2 bid, d1-14,q3w) or NX regimen (vinorelbine 25mg/m2 iv d1, 8 plus capecitabine 1000mg/m2 bid, d1-14, q3w) at the discretion of physicians for up to 6 cycles, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate and secondary endpoints included progression free survival (PFS), overall survival (OS). Results: 45 mTNBC patients, 27 in TX and 18 in NX were recruited, mostly (73.3%) as 1st line and the remaining as the 2nd line. The total objective response rate was 20.0% and clinical benefit rate was 62.2%. After a median follow-up of 28 months, PFS was 5.2 months (95%CI, 4.1-6.3mons) and OS was 18.2months (95%CI, 8.7-27.7mons). Almost half of the patients (22/45) progressed during treatment or within one month of the treatment discontinuation. PFS was significantly longer if patients got CR/PR (9.6 vs 4.3mons, P=0.015). When comparing two doublets, the response rate was numerically but not statistically lower in TX group than in NX group (14.8% vs 27.8%, P=0.449). Similarly, no difference was found in either PFS (4.9 vs 5.2 mons, P=0.483) or OS (21.5 vs 18.3 mons, P=0.964) between two regimens. Conclusions: Although the overall survival seems to be reasonable, efficacy of capecitabine-contained TX or NX regimen was relatively poor in terms of tumor remission and progression free survival in mTNBC patients, suggesting capecitabine may have limited potency in this subtype. These two combinations may be considered to be acceptable but may not be recommended as prior choice for mTNBC patients.

Envafolimab (KN035) in advanced tumors with mismatch-repair deficiency.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3021-3021
Author(s):  
Lin Shen ◽  
Jian Li ◽  
Yanhong Deng ◽  
Weijie Zhang ◽  
Aiping Zhou ◽  
...  
Keyword(s):  
Adverse Events ◽  
Mismatch Repair ◽  
Objective Response Rate ◽  
Interim Analysis ◽  
Response Rate ◽  
Objective Response ◽  
Open Label ◽  
Prior Therapy ◽  
Previously Treated

3021 Background: KN035 is a novel fusion protein of humanized anti-PD-L1 single domain antibody and human IgG1 Fc formulated for subcutaneous injection. This open-label phase II study evaluated the safety and antitumor activity of KN035 in patients with advanced microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) cancer. Methods: The study included patients aged ≥18 years with previously treated MSI-H/dMMR colorectal cancer (CRC) or other advanced solid tumors. MSI-H/dMMR status was assessed centrally for CRC and gastric cancer (GC) and locally for other tumors. KN035 was administered at 150 mg once weekly until progression, unacceptable toxicity, or withdrawal. Tumor assessments were every 8 weeks. The primary endpoint was the objective response rate per RECIST v1.1 by independent radiology review. The primary efficacy population (PEP) included patients with CRC who failed fluoropyrimidine (F), oxaliplatin (O), and irinotecan (I) plus those with advanced GC who had failed at least one prior systemic treatment. This was a planned interim analysis performed after the first 50 patients in the PEP had at least two on-study tumor assessments (PEPi). Results: As of December 17, 2019, 103 patients with MSI-H/dMMR advanced cancers were enrolled at 25 centers in China. The PEPi included 39 patients with CRC and 11 with GC, with a median follow-up of 7.5 months. The overall population included 65 patients with CRC (24 had prior therapy with F and O or I), 18 with GC, and 20 with other tumors, with a median follow-up of 6.7 months. The confirmed objective response rate was 30% (95% CI: 17.9%, 44.6%) in the PEPi, 54.2% (95% CI: 32.8%, 74.4%) in the CRC patients who had prior therapy with F and O or I, and 34.0% (95% CI: 24.9%, 44.0%) in the overall population. Of patients who had an objective response at the interim analysis, 80% of those in the PEPi, 84.6% of CRC patients who had prior therapy with F and O or I, and 85.7% of those in the overall population were still responding at the time of data cutoff. Median progression-free survival was 6.6 months in both the PEPi and the overall population. Median overall survival was not reached in either population. Fourteen (13.6%) patients had grade 3–4 treatment-related adverse events. No grade 5 treatment-related adverse events, pneumonitis, or colitis were reported. Local injection-site reactions, all grade 1 or 2, were reported in nine patients. Conclusions: Envafolimab demonstrated durable anti-tumor activity with a manageable safety profile in patients with previously treated advanced MSI-H/dMMR cancer. Clinical trial information: NCT03667170 .

First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study

2021 ◽  
Author(s):  
Heinz-Josef Lenz ◽  
Eric Van Cutsem ◽  
Maria Luisa Limon ◽  
Ka Yeung Mark Wong ◽  
Alain Hendlisz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Mismatch Repair ◽  
Clinical Benefit ◽  
Objective Response Rate ◽  
Low Dose ◽  
Response Rate ◽  
Objective Response ◽  
First Line

PURPOSE Nivolumab received US Food and Drug Administration approval as a single agent or in combination with ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan based on CheckMate 142. Presented are results of nivolumab plus low-dose ipilimumab in the first-line therapy cohort from the phase II CheckMate 142 study. PATIENTS AND METHODS Patients with no prior treatment in the metastatic setting for MSI-H/dMMR CRC were treated with nivolumab every 2 weeks plus low-dose ipilimumab every 6 weeks until disease progression. The primary end point was objective response rate (investigator assessment; RECIST v1.1). RESULTS Median age of treated patients was 66 years (N = 45). Median follow-up was 29.0 months. Objective response rate and disease control rate were 69% (95% CI, 53 to 82) and 84% (95% CI, 70.5 to 93.5), respectively, with 13% complete response rate. Median duration of response was not reached; 74% of responders had ongoing responses at data cutoff. Median progression-free survival and median overall survival were not reached with minimum follow-up of 24.2 months (24-month rates, 74% and 79%, respectively). Clinical benefit was observed regardless of baseline demographic and tumor characteristics, including BRAF or KRAS mutation status. In a post hoc analysis, of 14 patients who discontinued treatment and did not receive subsequent therapy, 10 remained progression-free. Patient-reported outcomes were stable over the treatment period. Grade 3-4 treatment-related adverse events occurred in 22% of patients; 13% discontinued because of any-grade treatment-related adverse events. CONCLUSION Nivolumab plus low-dose ipilimumab demonstrated robust and durable clinical benefit and was well tolerated as a first-line treatment for MSI-H/dMMR mCRC. Based on these promising data, randomized studies are warranted.

scholarly journals Randomized Phase II Trial of Vincristine-Irinotecan With or Without Temozolomide, in Children and Adults With Relapsed or Refractory Rhabdomyosarcoma: A European Paediatric Soft tissue Sarcoma Study Group and Innovative Therapies for Children With Cancer Trial

2021 ◽  
pp. JCO.21.00124
Author(s):  
Anne-Sophie Defachelles ◽  
Emilie Bogart ◽  
Michela Casanova ◽  
Johannes H. M. Merks ◽  
Gianni Bisogno ◽  
...  
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Adverse Events ◽  
Objective Response Rate ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival

PURPOSE The VIT-0910 trial was conducted to evaluate efficacy and safety of the vincristine-irinotecan combination with and without temozolomide (VIT and VI, respectively) in relapsed or refractory rhabdomyosarcoma (RMS). METHODS In this randomized European phase II trial, patients age 0.5-50 years received 21-day cycles combining vincristine (1.5 mg/m2 once a day on day 1 and day 8) and irinotecan (50 mg/m2 once a day from day 1 to day 5) with and without temozolomide (125 mg/m2 once a day from day 1 to day 5 and 150 mg/m2 once a day from cycle 2), until progression or unacceptable toxicity. The primary end point was objective response rate after two cycles. Secondary end points included best response, progression-free survival, overall survival, and adverse events. A Simon 2-stage design was initially planned to separately analyze 40 patients/arm. After amendment, the trial sample size was increased to 120 and a comparison between arms, adjusted for confounding factors, was added to the statistical plan (ClinicalTrials.gov, NCT01355445 ). RESULTS Overall, 120 patients (60 per arm) were recruited in 37 European centers. The median age was 11 years (range, 0.75-45); 89% of patients had a relapsed RMS. The objective response rate was 44% (24 of 55 evaluable patients) for VIT versus 31% (18 of 58) for VI (adjusted odds ratio, 0.50; 95% CI, 0.22 to 1.12; P = .09). The VIT arm achieved significantly better overall survival (adjusted hazard ratio, 0.55; 95% CI, 0.35 to 0.84; P = .006) compared with VI, with consistent progression-free survival results (adj-hazard ratio, 0.68; 95% CI, 0.46 to 1.01; P = .059). Overall, patients experienced adverse events ≥ grade 3 more frequently with VIT than VI (98% v 78%, respectively; P = .009), including a significant excess of hematologic toxicity (81% v 61%; P = .025). CONCLUSION The addition of temozolomide to VI improved chemotherapy efficacy for patients with relapsed RMS, with manageable increase in toxicity. VIT is considered the new standard treatment in these patients in the European paediatric Soft Tissue Sarcoma Group and will be the control arm in the next randomized trial.

The role of modified FOLFIRINOX regimen in unresectable advanced pancreatic cancer: A retrospective clinical study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15709-e15709
Author(s):  
Yuan Qian ◽  
Song Zheng ◽  
Changku Jia
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Objective Response Rate ◽  
Median Overall Survival ◽  
Response Rate ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
The United States ◽  
Grade 3

e15709 Background:Pancreatic cancer was the fourth leading cause of death from cancer in the United States in 2015, with a 5-year survival rate only 6%.More than 85% of patients has an unresectable disease at diagnosis for most patients remain asymptomatic. This population including locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC). Gemcitabine has been the standard treatment option for these patients for more than a decade, with a median overall survival nearly 6 months. In 2011, the phase 3 randomised controlled trial(PRODIGE 4/ACCORD 11) reported that FOLFIRINOX regimen had a significantly improved OS,PFS and a predominant ORR in patients with metastatic disease.FOLFIRINOX, as an encouraging regimen, its actual higher adverse events rate in clinical practice should not be underestimated, especially the grade 3/4 neutropenia and sensory neuropathy. The aim of our study is to explore whether a modified FOLFIRINOX regimen with the decrements of oxaliplatin and irinotecan had maintained efficacy and decreased grade 3/4 adverse events rate for the advanced pancreatic cancer. Methods:Retrospectively collected data of all patients carrying a diagnosis of advanced pancreatic cancer at the department of medical oncology, Hangzhou First People’s Hospital and Hangzhou cancer hospital between January 2014 and September 2016.The endpoint were overall survival, objective response rate and grade 3/ 4 adverse events. Results:Among 21 patients who received median 5(1-12) cycles modified FOLFIRINOX regimen,15 of total patients received this regimen for more than 4 cycles (71.4%). The median overall survival of MPC patients in this study is 12.6 months (95% CI, 6.2 months to 19 months). The objective response rate was 42.9%, with partial remission in 9 cases, stable disease in 8 cases and progression disease in 4 cases. Totally 8 patients had grade 3/4 adverse events, the most frequent were neutropenia (14.3%), neuropathy (14.3%) and diarrhea (9.5%). No chemotherapy-related death occurred. Conclusions:mFOLFIRINOX regimen in this study has maintained efficacy for its high objective response rate and an improved safety profile in patients with advanced pancreatic cancer.

A randomized phase II/III study comparing carboplatin and irinotecan with carboplatin and etoposide for the treatment of elderly patients with extensive-disease small cell lung cancer (JCOG1201/TORG1528).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8571-8571
Author(s):  
Tsuneo Shimokawa ◽  
Yuki Misumi ◽  
Hiroaki Okamoto ◽  
Yukio Hosomi ◽  
Isamu Okamoto ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Significant Difference ◽  
Elderly Japanese ◽  
Elderly Japanese Patients

8571 Background: Carboplatin and etoposide is the current standard treatment for elderly extensive-disease small-cell lung cancer (ED-SCLC). The purpose of this study is to evaluate the efficacy and safety of carboplatin and irinotecan compared with carboplatin and etoposide in elderly Japanese patients with ED-SCLC in a randomized phase II/III design. Methods: Eligibility included histologically or cytologically proven SCLC, no previous systemic chemotherapy, performance status of 0 to 2, and aged 71 years or older. Patients received carboplatin (AUC 5 mg/ml/min on day 1) and etoposide (80 mg/m2 on day 1 to 3) (CE) every 3 weeks for 4 cycles or carboplatin (AUC 4 mg/ml/min on day 1) and irinotecan (50 mg/m2 on day 1 and 8) (CI) every 3 weeks for 4 cycles. In the phase II part, the primary endpoint was the objective response rate of the CI arm and the secondary endpoint was adverse events. In the phase III part, the primary endpoint was overall survival, and the secondary endpoints were progression-free survival, objective response rate, adverse events, and symptom score. This study was designed to confirm the superiority of CI arm in terms of overall survival over CE arm. The median survival time with CI arm was expected to be increased by 3.5 months with hazard ratio (HR) of 0.750 (10.5 vs. 14.0 months). The sample size was set at 250 to observe the required number of events of 227 with one-sided alpha level of 0.05, a power of 70%, an accrual period of 6.5 years, and a follow-up period of 1.5 years. Results: Between December 2013 and June 2019, 258 patients were randomized (CE arm, 129 patients; CI arm, 129 patients). The median age was 75 (range, 71-90). The characteristics of the patients were well balanced between CE arm and CI arm. Overall survival, progression-free survival, and objective response rate of CE arm vs. CI arm were 12.0 (95% CI, 9.3-13.7) vs. 13.2 (95% CI, 11.1-14.6) months (HR, 0.848 (95% CI, 0.650-1.105)) (one-sided P=0.11), 4.4 (95% CI, 4.0-4.7) vs. 4.9 months (95% CI, 4.5-5.2) (HR, 0.851 (95% CI, 0.664-1.090)) (two-sided P=0.21), and 59.7% (77 of 129) vs. 64.3% (83 of 129), respectively. Symptom score showed no significant difference between the arms. Higher incidences of myelosuppression of grade 3 or worse occurred with CE arm, whereas higher incidences of gastrointestinal toxicity of grade 3 or worse occurred with CI arm. Three treatment-related deaths including lung infection in CE arm and lung infection and sepsis in CI arm were observed. Conclusions: Efficacy tended to be favorable in carboplatin and irinotecan arm, but there was no statistically significant difference. These results indicate that carboplatin and etoposide is a still standard treatment in elderly Japanese patients with ED-SCLC. Clinical trial information: 000012605.

Crizotinib Versus Chemotherapy on ALK-positive NSCLC: A Systematic Review of Efficacy and Safety

2018 ◽  
Vol 19 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Mingxia Wang ◽  
Guanqi Wang ◽  
Haiyan Ma ◽  
Baoen Shan
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Objective Response Rate ◽  
Retrospective Studies ◽  
Response Rate ◽  
Objective Response ◽  
Treated Group ◽  
Efficacy And Safety ◽  
Alk Positive

Introduction: Crizotinib was approved to treat anaplastic lymphoma kinase (ALK)- positive non-small cell lung cancer (NSCLC) by the Food and Drug Administration in 2011.We conducted a systematic review of clinical trials and retrospective studies to compare the efficacy and safety of crizotinib with chemotherapy. </P><P> Methods: We searched electronic databases from inception to Dec. 2016. Clinical trials and retrospective studies regarding crizotinib and crizotinib versus chemotherapy in treatment of NSCLC were eligible. The primary outcomes were the objective response rate (ORR) and disease control rate (DCR). Results: Nine studies (five clinical trials and four retrospective studies) including 729 patients met the inclusion criteria. Crizotinib treatment revealed 1-year OS of 77.1% and PFS of 9.17 months. And crizotinib had a better performance than chemotherapy in ORR (OR: 4.97, 95%CI: 3.16 to 7.83, P<0.00001, I2=35%). DCR revealed superiority with crizotinib than chemotherapy (OR: 3.42, 95% CI: 2.33 to 5.01, P<0.00001, I2=0%). PR (partial response) were significant superior to that of chemotherapy through direct systematic review. No statistically significant difference in CR (complete response) was found between crizotinib-treated group and chemotherapy-treated group. Regarding SD (stable disease), chemotherapy-treated group had a better performance than crizotinib-treated group. Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, nausea, and hematologic toxicity. This systematic review revealed improved objective response rate and increased disease control rate in crizotinib group comparing with chemotherapy group. Crizotinib treatment would be a favorable treatment option for patients with ALK-positive NSCLC. ALK inhibitors may have future potential applications in other cancers driven by ALK or c-MET gene mutations.

scholarly journals Concurrent chemoradiotherapy with S-1 compared with concurrent chemoradiotherapy with docetaxel and cisplatin for locally advanced esophageal squamous cell carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xi-Lei Zhou ◽  
Chang-Hua Yu ◽  
Wan-Wei Wang ◽  
Fu-Zhi Ji ◽  
Yao-Zu Xiong ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Esophageal Squamous Cell Carcinoma ◽  
Elderly Patients ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Response Rate ◽  
Locally Advanced ◽  
Grade 3

Abstract Background This retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods Patients with locally advanced ESCC who received CCRT with S-1 (70 mg/m2 twice daily on days 1–14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25 mg/m2) and cisplatin (25 mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Radiotherapy was delivered in 1.8–2.0 Gy per fraction to a total dose of 50–60 Gy. Treatment-related toxicities (Common Terminology Criteria for Adverse Events version 4.0), response rate, and survival outcomes were compared between groups. Results A total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3–4 adverse events were significantly lower in the S-1 group than that of the DP group (22.2% vs. 45.6%, p = 0.002). In the DP group, elderly patients (> 60 years) had a significantly higher rate of grade 3–4 adverse events than younger patients (58.1% vs. 31.3%, p = 0.01). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% vs. 25.0%, p = 0.275). Conclusion CCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.

Nivolumab in advanced esophageal squamous cell carcinoma (ATTRACTION-1/ONO-4538-07): Minimum of five-year follow-up.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 207-207
Author(s):  
Ken Kato ◽  
Yuichiro Doki ◽  
Takashi Ura ◽  
Yasuo Hamamoto ◽  
Takashi Kojima ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Squamous Cell ◽  
Group Performance ◽  
Objective Response

207 Background:ATTRACTION-1/ONO-4538-07 (AT-1), an open-label, single-arm, multicenter phase 2 clinical trial conducted in Japan, evaluated the clinical activity and safety of nivolumab in patients with advanced esophageal squamous cell carcinoma (ESCC) refractory/intolerant to fluoropyrimidine-, platinum-, and taxane-based chemotherapy. We previously reported the 2-year follow-up findings of AT-1, in which nivolumab demonstrated antitumor activity with a manageable safety profile for these patients. Here we report the final findings from AT-1 at a minimum follow-up of 5 years. Methods:Patients aged ≥20 years with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 received 3 mg/kg nivolumab intravenously every 2 weeks in 6-week cycles until disease progression or unacceptable toxicity. The primary endpoint was centrally-assessed objective response rate (ORR), defined as the proportion of patients whose best overall response was either a complete or partial response. Secondary endpoints included overall survival (OS), investigator-assessed ORR, progression-free survival (PFS), change in tumor burden, time to response, time to disease progression, and duration of response. Results:Between February 25 and November 14, 2014, a total of 65 patients were enrolled. Sixty-four patients were evaluated for the efficacy, and all patients were evaluated for the safety. At the final database lock on August 6, 2020, 11 (17.2%, 95% confidence interval [CI] 9.9-28.2) of 64 patients had an objective response by central assessment. The median OS was 10.8 months (95% CI, 7.4-13.9), and the estimated 5-year OS rate was 6.3% (95% CI, 2.0-14.0). The median PFS was 1.5 months (95% CI, 1.4-2.8), and the estimated 5-year PFS rate was 6.8% (95% CI, 2.2-15.1). Treatment-related adverse events that occurred with a frequency of > 10% were diarrhea and rash. The presentation will include characteristics of long-term survivors as well as detailed efficacy and safety data of nivolumab. Conclusions:This final assessment represents the longest follow-up of patients with advanced ESCC treated with nivolumab. Nivolumab demonstrated continued long-term efficacy in these patients based on a minimum of 5-year long-term survival update of AT-1. Furthermore, no new safety signals with nivolumab were identified during long-term follow-up. These findings are consistent with those of nivolumab monotherapy for various types of cancer. Clinical trial information: No.142422.

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