ATTRACTION-2 Trial Research Articles

Nivolumab in unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma.

Esophageal cancer (EC) is the eighth most common cancer worldwide. In view ofbiology and anatomical restrictions, multimodality treatment strategies have been developed for EC. However, the prognosis of patients with advanced EC remains especially poor. Immunotherapy, such as PD-1/PD-L1 and CTLA-4/B7 blockade, has emerged as a potent treatment for many types of cancer and has been approved in many countries. Based on the results of the ATTRACTION-3 trial, nivolumab, an anti-PD-1 monoclonal antibody, was approved by the US FDAfor patients with platinum-resistant, unresectable, recurrentor metastatic esophageal squamous cell carcinoma. The CheckMate 648 trial demonstrated that the combination of nivolumab with platinum-based fluoropyrimidine chemotherapy and combination immunotherapy with nivolumab and ipilimumab, an anti-CTLA-4 monoclonal antibody, showed a survival benefit in patients with advanced esophageal squamous cell carcinomacompared with doublet chemotherapy. This review focuses on nivolumab-containing treatments for patients with advanced esophageal squamous cell carcinoma.

Comparison of efficacy and safety of salvage-line nivolumab monotherapy between 240 and 480 mg for advanced esophageal squamous cell carcinoma.

317 Background: Nivolumab monotherapy was established as the standard second-line treatment of advanced esophageal squamous cell carcinoma (ESCC) based on the results of the ATTRACTION-3 trial. Initially, fixed dosing of 240 mg every two weeks (240) was used according to the results of the ATTRACTION-3 trial in Feb 2020. After that, fixed dosing of 480 mg every four weeks (480) was available in clinical practice according to pharmacokinetic data on advanced melanoma in Sep 2020. However, there were little data on the efficacy and safety of these dosing for advanced ESCC patients. Methods: We retrospectively reviewed data from ESCC patients who received nivolumab monotherapy for second or later-line at our institution. We evaluated progression-free survival (PFS), objective response rate (ORR), and the incidence rate of adverse events (AEs) compared between 240 and 480. Cox proportional regression model, Fisher’s exact tests, and t-tests were used for analysis. Results: We identified 117 patients as the subject of this study. Patients characteristics in 2nd line were as followed (240 vs 480); the median age (range): 68(46-85) vs 68.5(51-84) years old, PS (0/1/2): 34/61/5% vs 54/42/4%, taxane refractory cases: 18.6 vs 53.8%. In 3rd or later line; the median age (range): 63.5(47-85) vs 58(46-80) years old, PS (0/1/2): 28/60/12% vs 14/86/0%, taxane refractory cases: 72 vs 71.4%. The ORR were 11.9 vs 24.0% in 2nd line (p=0.19), and 0 vs 14.3% in 3rd or later line (p=0.22). The median PFS was 1.7 vs 4.1 months in 2nd line (HR = 0.60; [95% CI: 0.35-1.01; p = 0.056]), and 1.4 vs 1.8 months in 3rd or later line (HR = 0.58; [95% CI: 0.23-1.46; p = 0.25]). The all-grade AEs in 58.3 vs 69.7 were observed; rash 16.7 vs 6.1%, diarrhea 9.5 vs 6.1%, adrenal insufficiency 3.6 vs 6.1%, and interstitial pneumonia 3.6 vs 15.2%. There were no treatment-related deaths. Conclusions: In this study, fixed dosing of nivolumab in 240mg and 480mg showed comparable outcomes on efficacy and safety.

Nivolumab Combination Therapy for the Treatment of Unresectable Advanced or Metastatic Oesophageal Squamous Cell Carcinoma

Oesophageal cancer (OC) is the seventh most common malignancy worldwide, and there are few effective treatment options for advanced OC. Fluoropyrimidine and platinum-based chemotherapy has been the standard first-line treatment for advanced oesophageal squamous cell carcinoma (OSCC) but the survival outcomes are poor. Therefore, there is a need to develop new, more effective drugs. Immune checkpoint inhibitors (ICIs) have emerged as a new standard treatment for several malignancies. Nivolumab, a human monoclonal immunoglobulin G4 antibody that inhibits programmed cell death protein-1, has been developed for the treatment of advanced OSCC. Nivolumab monotherapy demonstrated clinical efficacy and safety in patients with OSCC in the ATTRACTION-3 trial, and was approved by the United States Food and Drug Administration as later-line treatment for patients with previously treated OSCC, regardless of programmed cell death protein-1 ligand expression status. Recently, the CheckMate 648 trial demonstrated the efficacy and safety of both an ICI in combination with chemotherapy, and a dual ICI combination, as first-line treatment for patients with advanced OSCC. This review discusses the current status of nivolumab combination therapy for patients with advanced OSCC, and future perspectives.

Recent Progress in Immunotherapy for Gastric Cancer

Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Under the standard of care, patients with advanced GC (AGC) have a median survival time of approximately 12-15 months. With the emergence of immunotherapy as a key therapeutic strategy in medical oncology, relevant changes are expected in the systemic treatment of GC. In the phase III ATTRACTION-2 trial, nivolumab, a monoclonal anti-programmed cell death 1 (PD-1) antibody, as a third- or later-line treatment improved overall survival (OS) compared with placebo in patients with AGC. Furthermore, nivolumab in combination with 5-fluorouracil and platinum as a first-line treatment improved OS in patients with human epidermal growth factor receptor-2 (HER2)-negative AGC in the global phase III CheckMate-649 study. Another anti-PD-1 antibody, pembrolizumab, in combination with trastuzumab and cytotoxic chemotherapy as a first-line treatment, significantly improved the overall response rate in patients with HER2-positive AGC. Therefore, immune checkpoint inhibitors (ICIs) are essential components of the current treatment of GC. Subsequent treatments after ICI combination therapy, such as ICI rechallenge or combination therapy with agents having other modes of action, are being actively investigated to date. On the basis of the success of immunotherapy in the treatment of AGC, various clinical trials are underway to apply this therapeutic strategy in the perioperative and postoperative settings for patients with early GC. This review describes recent progress in immunotherapy and potential immunotherapy biomarkers for GC.

105P The efficacy of nivolumab monotherapy for advanced gastric cancer depends on the HER2 status

The ATTRACTION-2 trial demonstrated the survival benefits of nivolumab in heavily treated advanced gastric cancer. Moreover, nivolumab has been approved for third- or later line treatment regardless of the human epidermal growth factor receptor 2 (HER2) status. However, there is limited information about variations in the efficacy of nivolumab according to the HER2 status. This study aimed to assess the differences in the efficacy of nivolumab between HER2-positive and -negative population for advanced gastric cancer.

Role of Nivolumab in the Management of First-Line Unresectable Advanced or Recurrent Gastric Cancer in Combination with Chemotherapy: Lessons from the Japanese Experience.

Recently, immune checkpoint inhibitor (ICI), such as anti-programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) monoclonal antibodies, has provided clinical benefits in various cancer types including advanced gastric cancer (AGC). Nivolumab, a monoclonal anti-PD-1 antibody, firstly showed an improvement in the overall survival (OS) in patients with AGC in the ATTRACTION-2 trial. Recently, chemotherapy plus nivolumab, as a first-line treatment for AGC, showed both OS and progression-free survival (PFS) benefits in patients with PD-L1 combined positive score (CPS) ≥5 in the global CheckMate-649 trial, and demonstrated PFS benefit irrespective of CPS status in the Asian ATTRACTION-4 trial. Based on these results, chemotherapy plus nivolumab in a first-line treatment was approved worldwide. However, the approval requirements and recommendations are different according to the approval agent or country. Thus, this review summarized the clinical trials of chemotherapy plus anti-PD1 antibody as a first-line treatment and focused on the role of nivolumab combined with chemotherapy mainly from the viewpoint of the Japanese experience.

496. THE OUTCOMES OF NIVOLUMAB FOR ESOPHAGEAL CANCER RECURRENT PATIENTS AFTER NAC-DCF THERAPY

Abstract Cancer immune therapy is the most prominent topic in esophageal cancer. The attraction-3 trial showed that nivolumab was associated with a significant improvement in overall survival versus chemotherapy. This trial was well designed, including patients unresectable, after surgery, and after chemoradiotherapy. However, there are few reports limited to the recurrence after surgery. Here we report the outcome of Nivolumab for the recurrence after surgery with docetaxel, cisplatin, and 5-FU neoadjuvant chemotherapy (NAC-DCF). The subjects were esophageal cancer recurrent patients after NAC-DCF, except for the cases performed only best supportive care, in Okayama University Hospital between January 2014 and October 2021, excepted the cases performed only best supportive care. We assessed their background characteristics, treatment details, immune-related adverse events (irAE), and overall survival (OS). 17 patients received therapies, including Nivolumab (Nivo). 41 patients received other chemotherapies (Control). There was no significant difference in gender (Nivo: male 88%, Control male 80%), age (Nivo: 68.1±8.9, Control: 65.1±5.6), and the period from surgery to recurrence (Nivo: 5.7±3.8 months, Control: 6.1±3.7 months). The Median overall survivals were 27±7.0 months and 18±2.5 months (P=0.055, Log Rank test). The major irAEs were reported in 4 cases (ACTH deficiency: 1 event, enterocolitis: 1 event, liver dysfunction: 2 events). Nivolumab improved the outcomes of recurrent patients after NAC-DCF with a bit of tendency.

P41-5 A case of advanced gastric cancer treated successfully with nivolumab

ATTRACTION-2 trial showed that nivolumab significantly prolonged overall survival compared with Best Supportive Care, with a median overall survival of 5.26 months. We report a case of gastric cancer with peritoneal dissemination that has achieved long-term survival of 2 years or more after administration of nivolumab.

Cost-Effectiveness of Nivolumab Immunotherapy vs. Paclitaxel or Docetaxel Chemotherapy as Second-Line Therapy in Advanced Esophageal Squamous Cell Carcinoma in China.

This study aimed to evaluate and compare nivolumab's cost-effectiveness with chemotherapy in patients with advanced esophageal squamous cell carcinoma from the Chinese healthcare system perspective. To this end, the researchers utilized a partitioned survival model with three mutually exclusive health stages. The characteristics of the patients used as inclusion and exclusion criteria in this model were the same as those used for patients with advanced esophageal squamous cell carcinoma in the ATTRACTION-3 study. The ATTRACTION-3 trial, which took place between January 7, 2016 and November 12, 2018, also yielded important clinical data. Data on medical and economic preferences were collected from real-world clinical practices. Costs, quality-adjusted life years, and incremental cost-effectiveness ratio were calculated for the two therapy options. The model uncertainty was investigated using a deterministic and probabilistic sensitivity analysis. When compared to chemotherapy, nivolumab was linked with an increase of 0.28 quality-adjusted life years with an increased cost of US$ 36,956.81 per patient in the base case analysis of a hypothetical sample of 419 patients. The incremental cost-effectiveness ratio in the deterministic sensitivity analysis was US$ 132,029.46/quality-adjusted life year, with a 48.02% probability of being cost-effective at willingness-to-pay thresholds of US$ 132,029.22/quality-adjusted life year. The incremental cost-effectiveness ratio remained greater than US$ 80,000/quality-adjusted life year in the deterministic sensitivity analyses. To be more cost-effective and remain below the threshold of 37,653 US$/quality-adjusted life year, which the Chinese population can afford, nivolumab's price would have to be lowered sharply by 53.50%. Nivolumab is clinically beneficial but not cost-effective when compared to chemotherapy. A substantial reduction in nivolumab's drug acquisition cost would be necessary to make it cost-effective for immunotherapy.

Correlation of combined positive score of PD-L1 expression and clinical efficacy for advanced esophageal squamous cell carcinoma treated with nivolumab monotherapy.

289 Background: Based on the results of the ATTRACTION-3 trial, nivolumab has shown superiority compared to taxane monotherapy as second-line treatment for advanced esophageal squamous cell carcinoma (ESCC) patients (pts). However, the PD-L1 expression by tumor proportion score (TPS) did not obviously correlate to the efficacy. In contrast, PD-L1 expression by combined positive score (CPS) was used as a companion diagnosis for pembrolizumab in ESCC. There are little data on CPS with nivolumab in ESCC. Methods: We retrospectively reviewed the medical records of the pts with ESCC who received nivolumab monotherapy in our hospital. The CPS before nivolumab was evaluated by 22C3 antibody. We evaluated the correlation of CPS and clinical efficacy of progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR) by using Cox proportional regression model and Fisher’s exact test. Results: Eighty-seven pts were selected for this analysis with a median follow-up time of 7.9 (1.2-84.1) months. Thirty pts (34.5%) had CPS < 10, and 57 patients (65.5%) had CPS≥10. Between two groups, the characteristics were as follows; median age (range): 62 (35-85) and 66 (46-85) years, PS 0: 20.0/36.8%, prior taxane: 50.0/40.4%, prior radiotherapy: 86.7/77.2%, respectively. The median PFS (95%CI) were 1.8 (1.2-2.8)/2.6 (1.8-33.8) months (HR: 0.85 [0.52-1.38], p = 0.50). The ORR/DCR were 21.1/31.6% in CPS < 10 group, and 22.2/57.8% in CPS≥10 group, and there was no statistical significance, respectively (p = 1.0/0.10). In multivariate analysis, only higher age was the favorite factor for PFS. From the result with another cut-off level of CPS, the proportion of CPS≥1/CPS≥20 was 90.8/36.8%. The HR of multivariate analysis with CPS≥1/CPS≥20 was 1.24/0.73, respectively. Conclusions: There was a trend toward better PFS with a higher cut-off point of CPS. CPS had the potential to be a biomarker even for nivolumab for advanced ESCC pts.

Immunotherapy for Peritoneal Metastases from Gastric Cancer: Rationale, Current Practice and Ongoing Trials.

Peritoneal metastases from gastric cancer play a key role in the fatal prognosis of the disease. The lack of efficacy of actual therapeutic approaches together with the outcomes achieved with checkpoint inhibitors in gastric cancer compel us to address the current state-of-the-art immunotherapy treatment of peritoneal dissemination. The immunogenicity of the peritoneum has been described to be particularly active at omentum and peritoneal lymph nodes. Also, both innate and acquired immunity seems to be involved at different molecular levels. Recent works show PDL1 expression being less present at the peritoneal level; however, some clinical trials have begun to yield results. For example, the ATTRACTION-2 trial has demonstrated the activity of Nivolumab in heavily pretreated patients even though peritoneal metastases were diagnosed in a 30% of them. Despite positive results in the metastatic setting, peritoneal responses to systemic checkpoint inhibitors remains unclear, therefore, new strategies for intraperitoneal immunotherapy are being proposed for different ongoing clinical trials.

SY5-5 Real-world data in the era of immune checkpoint inhibitors

Oesophageal cancer is the seventh most common cancer globally, and the sixth most common cause of death from cancer. The standard treatment for metastatic esophageal cancer after progression on for 1st line chemotherapy is nivolumab monotherapy in Japan. Survival benefit of nivolumab therapy occurred regardless of tumour PD-L1 expression in the ATTRACTION-3 trial. On the other hand, pembrolizumab was approved for metastatic, squamous cell carcinoma of the esophagus whose tumors express PD-L1 (Combined Positive Score [CPS] >10). Real world data after approval of nivolumab and pembrolizumab is not accumulated enough. Based on data of immune check inhibitors from clinical practice, it is warranted to discuss about the future treatment strategies of oesophageal cancer in the era of immune checkpoint inhibitors.

P-182 A multicenter study of prognostic factors in nivolumab monotherapy for advanced or recurrent esophageal cancer

Based on the results of the ATTRACTION-3 trial, nivolumab monotherapy is regarded as the standard of treatment for the patients with unresectable advanced or recurrent esophageal cancer (EC) who are refractory or intolerant to fluoropyrimidines and platinum-based chemotherapy. However, the prognostic factors for EC treated with nivolumab are still unclear. Inflammation-based prognostic scores have generally been reported to be useful in the prognosis of various cancers. This study investigated whether inflammation-based prognostic scores were also useful in EC treated with nivolumab monotherapy.

MO5-3 Nivolumab monotherapy in 3rd-line treatment for HER2 positive or negative advanced gastric cancer

Trastuzumab deruxtecan (DS-8201) showed clinical benefit among HER2 positive (H+) advanced gastric cancer (AGC) patients who received at least two previous therapies. Subgroup analysis of ATTRACTION-2 trial showed that nivolumab was efficacious regardless of prior Trastuzumab use. Little is known about proper use of nivolumab, trifluridine/tipiracil, and DS-8201 in 3rd-line treatment. The purpose of this study is to compare nivolumab efficacy between H+ and HER2 negative (H-) AGC patients in clinical practice. We retrospectively reviewed the medical record of 38 AGC patients who received nivolumab monotherapy in 3rd-line treatment at our institution until August 2020. The baseline characteristics of H+ group (n=10)/ H- group (n=28) were as follows: median age, 71/69 years; male, 90%/68%; ECOG PS 0-1, 80%/79%; previous gastrectomy, 20%/29%; intestinal type, 60%/43%; liver meta, 50%/32%; and ascites, 40%/54%. All H+ patients had received trastuzumab. Among 6 in H+ group/ 16 in H- group who had measurable lesions, objective response rate was 33%/19%. Median progression-free survival and median overall survival were 3.5/1.8 months and 8.2/7.5 months, respectively. The frequencies of immune-related adverse events between two groups were similar (20%/14%). H+ was associated with better outcome of nivolumab monotherapy compared with H-, although this study was small sample size and single institutional retrospective analysis.

PCN34 Comparative Effectiveness of Docetaxel and Paclitaxel in Advanced Esophageal Squamous Cell Carcinoma Refractory or Intolerant to Previous Chemotherapy: Propensity Score-Matching Analyses from Attraction-3 Trial

In the Phase 3 ATTRACTION-3 trial, nivolumab demonstrated a significant survival benefit versus paclitaxel/docetaxel for patients with advanced esophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy. Due to lack of stratification with respect to investigator’s choice of chemotherapy in the trial, this analysis investigated the comparative efficacy of docetaxel and paclitaxel. Data from the control arm (n=209) with minimum 18-month follow-up was used where 65 patients were treated with docetaxel and 144 patients were treated with paclitaxel. A propensity score matching using inverse-probability-weighted regression adjustment was performed to balance the distribution of baseline covariates including age, gender, race, BMI, ECOG performance status, disease stage, secondary lesions, prior treatments, PD-L1 status, number of organ metastases, presence of recurrent disease, geographic location, and best response to most recent regimen. Reduction in potential selection bias was assessed via global overidentification test and standardized differences between raw and weighted characteristics. Outcome measures included overall survival (OS), progression-free survival (PFS), and duration of treatment (DoT). Analyses were conducted in Stata v13.0. Matching successfully raised the extent of overlap between the distribution of propensity scores (p-value = 0.98 from the overidentification test for covariate balance) and reduced the median standard bias from 9.1% to 2.7%. Post-matching, there were no statistically significant differences between docetaxel and paclitaxel for any of the endpoints analyzed (<1 month differential in restricted mean durations in all endpoints) where the resulting HRs and 95% confidence intervals were: 1.05 [0.60, 1.83] for OS, 0.88 [0.50, 1.54] for PFS and 0.83 [0.50, 1.38] for DoT. Post-matching effective sample sizes for docetaxel and paclitaxel arms were 24 and 40, respectively. Demonstrably comparable efficacy of docetaxel and paclitaxel can enable statistically more robust survival analyses from the control arm of ATTRACTION-3 trial and maintain randomization for subsequent network meta-analyses.

PCN43 Cost-Effectiveness of Nivolumab for the Treatment of Advanced Esophageal Squamous Cell Carcinoma Refractory or Intolerant to Previous Chemotherapy: A United-States Payer Perspective

To evaluate the cost-effectiveness of nivolumab versus taxane-based chemotherapy (TbC) for previously treated advanced esophageal squamous cell carcinoma (aESCC) patients from a United States (US) payer perspective using data with minimum 36-months follow-up from the ATTRACTION-3 trial.

Impact of PD-L1 combined positive score (CPS) on clinical response to nivolumab in patients with advanced esophageal squamous cell carcinoma.

e16045 Background: The ATTRACTION-3 trial showed that nivolumab (Nivo) significantly improved overall survival (OS) of patients (pts) with previously treated advanced esophageal squamous cell carcinoma (ESCC) regardless of tumor programmed cell death ligand-1 (PD-L1) expression assessed with tumor proportion score (TPS). On the other hand, pembrolizumab prolonged OS in advanced esophageal carcinoma pts with combined positive score (CPS) of ≥ 10 in the KEYNOTE-181 trial. Whether CPS can predict clinical outcome of Nivo in advanced ESCC pts remains unclear. Methods: We retrospectively evaluated advanced ESCC pts who received Nivo at a single institution between January 2014 and September 2020. The main eligibility criteria were as follows: refractory or intolerant to fluoropyrimidines and platinum, no prior anti-PD-1/PD-L1 antibody treatment, no comorbid malignancies, and available tissue specimens obtained before initiation of Nivo. PD-L1 immunostaining was performed using PD-L1 IHC 22C3 pharmDx assay, and the tumors were classified into three groups depending on CPS (≥ 10, 1–10, &lt; 1). The adjusted hazard ratios (aHRs) for progression-free survival (PFS) and OS were calculated using a multivariate Cox model that contained variables with p values &lt; 0.05 in the univariate analysis. Results: Among 69 pts, 50 were eligible (CPS ≥ 10/CPS 1–10/CPS &lt; 1, 23/18/9). Patient characteristics were as follows (CPS ≥ 10/CPS 1–10/CPS &lt; 1): age, ≥ 65, 70/67/67%; male, 83/67/78%; PS ≥ 1, 61/72/44%; second-line treatment, 65/61/56%; disease status, recurrent, 61/33/78%; prior esophagectomy, 65/33/44%; prior radiotherapy, 57/56/56%; prior taxane, 52/28/44%; the number of metastatic sites, ≥ 2, 48/61/89%; lymph node metastasis, 78/83/89%, lung metastasis, 26/22/56%; liver metastasis, 17/17/44%. Among 42 pts (84%) with disease progression after Nivo treatment, 24 pts received salvage-line chemotherapy. The adjustment factor for PFS was liver metastasis, while that for OS was not detected. The median PFS was 4.1 months (mo) in CPS ≥ 10 and 2.5 mo in CPS 1–10 (HR vs. CPS ≥ 10, 1.06; 95% CI, 0.51–2.17; p = 0.864; aHR, 1.15; 95% CI, 0.54–2.36; p = 0.713), and 1.4 mo in CPS &lt; 1 (HR vs. CPS ≥ 10, 3,78; 95% CI, 1.53–8.92; p = 0.005; aHR, 1.91; 95% CI, 0.67–5.39; p = 0.223). The median OS was 12.3 mo in CPS ≥ 10, 10.2 mo in CPS 1–10 (HR vs. CPS ≥ 10, 1.72; 95% CI, 0.75–4.00; p = 0.201), and 9.0 mo in CPS &lt; 1 (HR vs. CPS ≥ 10, 2.31; 95% CI, 0.92–5.69; p = 0.075). Objective response rate (CPS ≥ 10/CPS 1–10/CPS &lt; 1) in 40 pts who had measurable lesions were 32/25/0%, respectively. Conclusions: The pts with CPS of &lt; 1 did not respond to Nivo. Our study suggests that CPS is useful for predicting response to Nivo in pts with advanced ESCC.[Table: see text]

Survival analysis by tumor response from real-world data in advanced gastric cancer treated with nivolumab: The DELIVER trial (JACCRO GC-08).

4044 Background: The phase III ATTRACTION-2 trial demonstrated survival benefit of nivolumab (Nivo) as third- or later-line treatment in previously treated advanced gastric or gastroesophageal junction (GEJ) cancer, with response rate (RR) of 11% (Kang YK, et al. Lancet 2017). It has been shown that some tumors grow rapidly after Nivo treatment, but the proportion and survival are still uncertain. We therefore prospectively investigated clinical outcomes from real-world data of Nivo treatment in advanced gastric cancer (GC). Methods: The DELIVER trial was a prospective, multicenter, observational study which assessed patients (pts) with advanced gastric or GEJ adenocarcinoma treated with Nivo alone and ECOG PS 0-2 (UMIN000030850). The aims were to evaluate the efficacy and safety of Nivo treatment in real world. Primary endpoint was overall survival (OS), secondary endpoints were RR, disease control rate (DCR), progression-free survival (PFS), tumor growth rate (TGR) at 1st evaluation, and safety. The sub-group analyses were performed for survival according to tumor response and clinical factors. The survival data was fixed at the timepoint of 1 year after the last enrollment. Results: In 501 pts enrolled from Mar 2018 to Aug 2019, 487 pts were evaluable (median age 70y, 71% male, ECOG PS0/1/2 42/44/14%, no. of prior regimen 1/2/≥3 2/39/59%, 21% HER2-pos, 42% pts with ascites). Median OS was 5.8 months (m) (95%CI 5.3-7.0) with 1y-survival rate of 30%, and median PFS was 1.8 m (95%CI 1.7-2.0), at 454 events for PFS and 389 events for OS. The DCR were 39.4%, and RR was 14.2% in 282 pts with measurable lesions. Median OS and PFS by tumor response (CR/PR/SD/PD) were Not Reached (NR)/NR/11.3/4.1m and NR/11.7/3.8/1.4m, respectively. A sub-group analysis of OS by clinical factors is the following: male/female; 6.5/5.0m ( p= 0.002), tub/por/sig; 8.1/5.4/4.1m ( p&lt; 0.0001), albumin &lt; 3.5/≥3.5; 4.2/8.9m ( p&lt; 0.0001), w/peritoneal mets/w/o; 4.9/8.4m ( p&lt; 0.0001), and w/ascites/w/o; 3.7/8.9m ( p&lt; 0.0001). These findings were also observed in PFS. In 219 evaluable pts for TGR, 20.5% pts were identified as hyper-progressive disease (HPD). An exploratory approach by logistic regression analysis indicated that level of free-T3 in blood before Nivo treatment was higher in the HPD compared to the non-HPD group (2.5 vs. 2.2 pg/ml, p= 0.005). Survival time was comparable between the HPD group and PD without HPD group. Median period from 1st evaluation to death was 2.8 m for HPD, 5.7 m for non-HPD, and 2.4 m for PD at 1st evaluation without HPD. Conclusions: The real-world data of Nivo treatment in advanced GC indicated comparable survival to previous result in a clinical trial. Differences in survival time by tumor response or some clinical factors were observed in Nivo treatment. In addition, our study revealed the rate of HPD and the prognosis in advanced GC pts treated with Nivo. Clinical trial information: UMIN000030850.

Retrospective study of nivolumab monotherapy for advanced esophageal squamous cell carcinoma.

179 Background: Based on the results of the ATTRACTION-1 and ATTRACTION-3 trials, nivolumab monotherapy has used for the treatment of metastatic or recurrence esophageal cancer patients who were refractory or intolerant to fluoropyrimidine and platinum since February 2020 in Japan. However, the ATTRACTION-1 trial mainly included patients who received nivolumab monotherapy as third or later-line treatments, which was different from the ATTRACTION-3 trial which mainly included patients as second-line treatment. Therefore, it is still unclear whether the treatment lines affect the efficacy of nivolumab in clinical practice. Methods: Medical records were retrospectively reviewed for patients diagnosed with metastatic or recurrence esophageal squamous cell carcinoma (ESCC) who received nivolumab monotherapy as second- or third or later-line treatments in our hospital. We evaluated progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) based on the RECIST ver1.1, and the incidences of adverse events (AEs) based on the CTCAE ver5.0. Results: Sixty-two patients were identified as the subject of this study. Thirty patients received nivolumab as second-line treatment (48.4%) and 32 patients as third or later-line treatments (51.6%). The median age (range) were 67 (33-80)/61 (52-84), PS 0 were 40.0/21.9%, prior taxane treatment rate were 6.7/93.8%, respectively. The ORR/DCR were 22.7/45.5% in second-line treatment, and 24.1/44.8% in third or later-line treatments (p=1.00). The median PFS (95% CI) was 2.3 (1.4-6.2)/2.3 (1.2-3.6) months in the second-/third or later-line treatments (HR=0.86, p=0.58). AEs of grade 3 or higher were observed in 6.7/6.3% of the second-/third or later-line treatments. Conclusions: There was no clear difference between second -line and third or later-line treatments in the short-term efficacy of nivolumab monotherapy in advanced ESCC patients.

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)

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.