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

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.

SUBMITTER: Satoh T

PROVIDER: S-EPMC8387268 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Five-year follow-up results from phase II studies of nivolumab in Japanese patients with previously treated advanced non-small cell lung cancer: pooled analysis of the ONO-4538-05 and ONO-4538-06 studies.

Project description:BackgroundTwo phase II studies in Japan examined the efficacy and safety of nivolumab, a programmed cell death 1 receptor inhibitor, in patients with advanced squamous and non-squamous non-small cell lung cancer (ONO-4538-05 and ONO-4538-06). We examined the long-term efficacy and safety of nivolumab in these patients treated for up to 5 years.MethodsPatients with squamous (N = 35) or non-squamous (N = 76) non-small cell lung cancer received nivolumab (3 mg/kg every 2 weeks) until disease progression/death. Overall survival and progression-free survival were assessed at 5 years after starting treatment in separate and pooled analyses. Safety was evaluated in terms of treatment-related adverse events.ResultsA total of 17 patients were alive at the database lock (26 July 2019). The median overall survival (95% confidence interval) and 5-year survival rate were 16.3 (12.4-25.2) months and 14.3% in squamous patients, 17.1 (13.3-23.0) months and 19.4% in non-squamous patients and 17.1 (14.2-20.6) months and 17.8% in the pooled analysis, respectively. Programmed death ligand-1 expression tended to be greater among 5-year survivors than in non-survivors (P = 0.0703). Overall survival prolonged with increasing programmed death ligand-1 expression, with 5-year survival rates of 11.8, 21.8 and 41.7% in patients with programmed death ligand-1 expression of <1, ≥1-<50 and ≥50%, respectively. Treatment-related adverse events in ≥10% of patients (pooled analysis) included rash (15.3%), malaise (14.4%), decreased appetite (14.4%), pyrexia (14.4%) and nausea (10.8%).ConclusionsLong-term survival with nivolumab was observed in patients with squamous or non-squamous non-small cell lung cancer. No new safety signals were reported after ≥5 years of follow-up.

| S-EPMC7767981 | biostudies-literature

Three-year follow-up results from phase II studies of nivolumab in Japanese patients with previously treated advanced non-small cell lung cancer: Pooled analysis of ONO-4538-05 and ONO-4538-06 studies.

Project description:BackgroundNivolumab is a programmed cell death 1 (PD-1) receptor inhibitor antibody that enhances immune system antitumor activity. It is associated with longer overall survival (OS) than the standard treatment of docetaxel in patients with previously treated advanced squamous (SQ) and non-squamous (non-SQ) non-small cell lung cancer (NSCLC). We previously conducted two phase II studies of nivolumab in Japanese patients with SQ (ONO-4538-05) and non-SQ (ONO-4538-06) NSCLC, showing overall response rates (ORRs) (95% CI) of 25.7% (14.2-42.1) and 22.4% (14.5-32.9), respectively, with acceptable toxicity. In this analysis, we more precisely estimated the long-term safety and efficacy in patients with SQ and non-SQ NSCLC by pooling data from these two trials.MethodsSQ (N = 35) and non-SQ (N = 76) NSCLC patients received nivolumab (3 mg/kg, every 2 weeks) until progression or discontinuation. OS was estimated using the Kaplan-Meier method. A pooled analysis of SQ and non-SQ patients was also performed.ResultsIn SQ NSCLC patients, the median OS (95% CI) was 16.3 months (12.4-25.2), and the estimated 1-year, 2-year, and 3-year survival rates were 71.4% (53.4-83.5), 37.1% (21.6-52.7), and 20.0% (8.8-34.4), respectively. In non-SQ NSCLC patients, median OS was 17.1 months (13.3-23.0), and the estimated 1-, 2-, and 3-year survival rates were 68.0% (56.2-77.3), 37.4% (26.5-48.1), and 31.9% (21.7-42.5), respectively. When SQ NSCLC and non-SQ NSCLC data were pooled, the median OS was 17.1 months (14.2-20.6), and the estimated 1-, 2-, and 3-year survival rates were 69.1% (59.6-76.8), 37.3% (28.3-46.2), and 28.1% (20.0-36.7), respectively. Twenty (76.9%) of 26 responders lived for 3 or more years. Nivolumab was well tolerated and no new safety signals were found.ConclusionTreatment with nivolumab improved long-term survival and was well tolerated in patients with SQ and non-SQ NSCLC.Trial registrationJapicCTI-132072; JapicCTI-132073.

| S-EPMC6718542 | biostudies-literature

First-line nivolumab plus ipilimumab or chemotherapy versus chemotherapy alone in advanced esophageal squamous cell carcinoma: a Japanese subgroup analysis of open-label, phase 3 trial (CheckMate 648/ONO-4538-50).

Project description:BackgroundProgrammed cell death 1 (PD-1)-based treatments are approved for several cancers. CheckMate 648, a global, phase 3 trial, showed that first-line nivolumab (anti-PD-1 antibody) plus ipilimumab (NIVO + IPI) or nivolumab plus chemotherapy (NIVO + Chemo) significantly increased survival in advanced esophageal squamous cell carcinoma (ESCC) without new safety signals versus chemotherapy alone (Chemo).MethodsWe evaluated the Japanese subpopulation of CheckMate 648 (n = 394/970), randomized to receive first-line NIVO + IPI, NIVO + Chemo, or Chemo. Efficacy endpoints included overall survival (OS) and progression-free survival assessed by blinded independent central review in Japanese patients with tumor-cell programmed death-ligand 1 (PD-L1) expression ≥ 1% and in all randomized Japanese patients.ResultsIn the Japanese population, 131, 126, and 137 patients were treated with NIVO + IPI, NIVO + Chemo, and Chemo, and 66, 62, and 65 patients had tumor-cell PD-L1 ≥ 1%, respectively. In patients with tumor-cell PD-L1 ≥ 1%, median OS was numerically longer with NIVO + IPI (20.2 months; hazard ratio [95% CI], 0.46 [0.30-0.71]) and NIVO + Chemo (17.3 months; 0.53 [0.35-0.82]) versus Chemo (9.0 months). In all randomized patients, median OS was numerically longer with NIVO + IPI (17.6 months; 0.68 [0.51-0.92]) and NIVO + Chemo (15.5 months; 0.73 [0.54-0.99]) versus Chemo (11.0 months). Grade 3-4 treatment-related adverse events were reported in 37%, 49%, and 36% of all patients in the NIVO + IPI, NIVO + Chemo, and Chemo arms, respectively.ConclusionSurvival benefits with acceptable tolerability observed for NIVO + IPI and NIVO + Chemo treatments strongly support their use as a new standard first-line treatment in Japanese patients with advanced ESCC.ClinicaltrialsGov idNCT03143153.

| S-EPMC10024660 | biostudies-literature

A subanalysis of Japanese patients in a randomized, double-blind, placebo-controlled, phase 3 trial of nivolumab for patients with advanced gastric or gastro-esophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2).

Project description:BackgroundNivolumab, an anti-programmed death-1 agent, showed survival benefits in Asian patients, including Japanese, with gastric/gastro-esophageal junction (G/GEJ) cancer. We report the analysis of the Japanese subpopulation from ATTRACTION-2 that evaluated nivolumab versus placebo in unresectable advanced or recurrent G/GEJ cancer after ≥ 2 chemotherapy regimens.MethodsData from the Japanese subpopulation in the randomized, double-blind, placebo-controlled, phase 3 trial were analyzed (data cutoff, February 25, 2017). Primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and objective response rate (ORR).ResultsAmong the overall study population of 493 patients, 226 (nivolumab 152; placebo 74) were enrolled from 28 sites in Japan. In the Japanese subset, median OS was longer with nivolumab versus placebo (5.4 months, 95% CI 4.6-7.4 versus 3.6 months, 95% CI 2.8-5.0). The risk of death was lower in the nivolumab versus placebo group (hazard ratio 0.58, 95% CI 0.42-0.78; p = 0.0002). Incidences of serious adverse events were 23% (35/152) and 25% (18/72) in the nivolumab and placebo groups, respectively. In the Japanese ITT population, 22% of nivolumab-treated and 28% of placebo-treated patients received prior ramucirumab treatment. Overall, clinical activity of nivolumab was observed regardless of prior ramucirumab use. In the nivolumab group, ORR and PFS were numerically higher in patients with prior ramucirumab use than in those without.ConclusionsIn the Japanese subpopulation, patients receiving nivolumab had longer OS, similar to the overall population, with a manageable safety profile. The interaction between nivolumab and ramucirumab will be clarified in ongoing clinical trials.

| S-EPMC6394726 | biostudies-literature

Nivolumab (anti-PD-1, BMS-936558, ONO-4538) in patients with advanced non-small cell lung cancer.

Project description: Not available

| S-EPMC4367666 | biostudies-literature

First-line nivolumab, paclitaxel, carboplatin, and bevacizumab for advanced non-squamous non-small cell lung cancer: Updated survival analysis of the ONO-4538-52/TASUKI-52 randomized controlled trial.

Project description:BackgroundONO-4538-52/TASUKI-52 was performed in Japan, Korea, and Taiwan to determine the oncological effectiveness and safety of combining nivolumab or placebo with bevacizumab plus platinum chemotherapy for the initial (first-line) treatment of patients with advanced non-squamous non-small cell lung cancer (nsNSCLC). At the interim analysis (minimum follow-up, 7.4 months), the independent radiology review committee-assessed progression-free survival was significantly longer in the nivolumab arm, but overall survival (OS) data were immature.MethodsHere, we present the updated OS data. Patients with treatment-naïve stage IIIB/IV or recurrent nsNSCLC without driver mutations in ALK, EGFR, or ROS1, were randomized 1:1 to receive either nivolumab or placebo. Patients in both arms received paclitaxel, carboplatin, and bevacizumab, administered 3-weekly for a maximum of 6 cycles. Nivolumab/placebo and bevacizumab were subsequently continued until disease progression or unacceptable toxicity.ResultsOverall, 550 patients were randomized. At the time of the analysis (minimum follow-up: 19.4 months), the median OS was longer in the nivolumab arm than in the placebo arm (30.8 vs. 24.7 months; hazard ratio 0.74, 95% confidence interval 0.58-0.94). The 12-month OS rates were 81.3% vs. 76.3% in the nivolumab vs. placebo arms, respectively. The respective 18-month OS rates were 69.0% vs. 61.9%.ConclusionNivolumab plus platinum chemotherapy and bevacizumab demonstrated longer OS vs. the placebo combination. We believe this regimen is viable as a standard, first-line treatment for patients with advanced nsNSCLC without driver mutations in ALK, EGFR, or ROS1.

| S-EPMC10501244 | biostudies-literature

Nivolumab versus chemotherapy in Japanese patients with advanced esophageal squamous cell carcinoma: a subgroup analysis of a multicenter, randomized, open-label, phase 3 trial (ATTRACTION-3).

Project description:BackgroundThe efficacy and safety of nivolumab versus chemotherapy was evaluated in the Japanese subpopulation from the overall intent-to-treat (ITT) population of the ATTRACTION-3 trial conducted in patients with advanced esophageal squamous cell carcinoma (ESCC) as second-line treatment.MethodsData from Japanese patients enrolled in the multicenter, randomized, open-label, phase 3 ATTRACTION-3 trial were analyzed. The primary endpoint was overall survival (OS). Secondary endpoints included duration of response (DOR), objective response rate (ORR), disease control rate (DCR), and safety. Exploratory subgroup analyses evaluated the association between OS and stratification factors/baseline variables.ResultsOverall, 274 (nivolumab, 136; chemotherapy, 138) of the 419 patients in ATTRACTION-3 were enrolled from Japan: response-evaluable population (107; 108) and safety population (135; 138). OS tended to be longer in the nivolumab group versus the chemotherapy group (median: 13.4 months vs. 9.4 months; HR, 0.77; 95% CI 0.59-1.01). Median DOR was longer in the nivolumab group (7.6 months) versus the chemotherapy group (3.6 months). ORRs were similar between the nivolumab [22.4% of patients (24/107)] and chemotherapy groups [22.2% (24/108); odds ratio, 0.98; 95% CI 0.52-1.87]. DCR was lower in the nivolumab group [41.1% (44/107)] versus the chemotherapy group [66.7% (72/108)]. OS in the exploratory analysis consistently favored the nivolumab group versus the chemotherapy group. Overall, nivolumab demonstrated favorable efficacy and safety versus chemotherapy in the Japanese subpopulation, and the trend was similar to that observed in the overall ATTRACTION-3 ITT population.ConclusionNivolumab represents a new standard second-line treatment option for Japanese patients with advanced ESCC.

| S-EPMC7794205 | biostudies-literature

Effectiveness of taxanes following nivolumab in patients with advanced esophageal squamous cell carcinoma: a retrospective chart review of patients in ATTRACTION-3.

Project description:BackgroundThe phase III ATTRACTION-3 study showed that second-line nivolumab monotherapy for advanced esophageal squamous cell carcinoma prolonged overall survival (OS) but did not improve progression-free survival (PFS). Subsequent systemic therapy after discontinuing nivolumab may affect these outcomes. To test this possibility, we evaluated the outcomes of treatment with taxanes after nivolumab in ATTRACTION-3.MethodsWe reviewed the charts of Japanese patients who had discontinued second-line nivolumab in ATTRACTION-3 and started subsequent third-line taxanes between January 7, 2016, and November 12, 2018. The primary endpoint was objective response rate (ORR) to third-line taxanes.ResultsOf the 75 patients included in this study, 54 (72%), 18 (24%), and 3 (4%) patients received either paclitaxel, docetaxel, or combination therapy comprising docetaxel, cisplatin, and 5-fluorouracil, respectively. The ORR in the overall, paclitaxel, and docetaxel groups was 29.6%, 36.5%, and 12.5%, respectively; these numbers were comparable to those (20-44%) in patients receiving taxanes as first- and second-line therapy. The median OS in the overall, paclitaxel, and docetaxel groups was 9.9, 9.9, and 9.3 months, respectively, whereas the corresponding median PFS was 4.9, 4.7 and 6.5 months, respectively. Treatment-related adverse events were observed in 65 (87%) patients, of which grade 3-4 occurred in 37 (49%) patients.ConclusionsFavorable effectiveness and safety profile of taxanes following second-line nivolumab was observed in Japanese patients with advanced esophageal squamous cell carcinoma. When a patient with advanced esophageal squamous cell carcinoma receiving nivolumab becomes refractory or intolerant, subsequent taxane treatment may be a promising option.

| S-EPMC10024664 | biostudies-literature

Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer.

Project description:PurposeProgrammed death 1 is an immune checkpoint that suppresses antitumor immunity. Nivolumab, a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody, was active and generally well tolerated in patients with advanced solid tumors treated in a phase I trial with expansion cohorts. We report overall survival (OS), response durability, and long-term safety in patients with non-small-cell lung cancer (NSCLC) receiving nivolumab in this trial.Patients and methodsPatients (N = 129) with heavily pretreated advanced NSCLC received nivolumab 1, 3, or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks. Tumor burden was assessed by RECIST (version 1.0) after each cycle.ResultsMedian OS across doses was 9.9 months; 1-, 2-, and 3-year OS rates were 42%, 24%, and 18%, respectively, across doses and 56%, 42%, and 27%, respectively, at the 3-mg/kg dose (n = 37) chosen for further clinical development. Among 22 patients (17%) with objective responses, estimated median response duration was 17.0 months. An additional six patients (5%) had unconventional immune-pattern responses. Response rates were similar in squamous and nonsquamous NSCLC. Eighteen responding patients discontinued nivolumab for reasons other than progressive disease; nine (50%) of those had responses lasting > 9 months after their last dose. Grade 3 to 4 treatment-related adverse events occurred in 14% of patients. Three treatment-related deaths (2% of patients) occurred, each associated with pneumonitis.ConclusionNivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC. Randomized clinical trials with nivolumab in advanced NSCLC are ongoing.

| S-EPMC4672027 | biostudies-literature

ONO-4538/CA2099X8 Phase 2/3 Study(ONO-4538-72/CA2099X8)

Project description:Intervention name : ONO-4538/BMS-936558 INN of the intervention : Nivolumab Dosage And administration of the intervention : Intravenous administration Control intervention name : Fluorouracil, Leucovorin Calcium Folinate, Oxaliplatin, Bevacizumab INN of the control intervention : Fluorouracil, Leucovorin Calcium Folinate, Oxaliplatin, Bevacizumab Dosage And administration of the control intervention : Intravenous administration Primary outcome(s): efficacy PFS Study Design: Randomized, open-label

| 2658327 | ecrin-mdr-crc

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