Safety Of Nivolumab In Patients Research Articles

Real-world safety of nivolumab in patients with malignant pleural mesothelioma in Japan: post-marketing surveillance study.

This post-marketing surveillance (PMS) was conducted to evaluate the incidence of adverse events with nivolumab in patients with unresectable, advanced or recurrent malignant pleural mesothelioma (MPM) that had progressed after first-line chemotherapy and to identify factors that potentially affected its safety in real-world clinical practice. Patients who had not received nivolumab previously were registered between November 2018 and February 2021. Nivolumab was given intravenously 240mg every 2weeks or 480mg every 4weeks. Patients were followed up for 6months after treatment initiation. Information on patient characteristics, treatment status, and adverse events was collected. This PMS enrolled 124 patients, involving 48 sites across Japan. At 6months, nivolumab therapy was ongoing in 35.5% of patients (44/124) and had been discontinued in 64.5% (80/124). The overall incidence of treatment-related adverse events (TRAEs) was 40.3%; the incidence of Grade 3 or higher TRAEs was 12.9%. The pattern of TRAEs based on System Organ Class categories was generally consistent with those seen in the Japanese phase II MERIT study. The most common Grade 3 or higher TRAEs were interstitial lung disease (2.4%), lung disorder, and diarrhea (each 1.6%). The incidence of TRAEs was significantly higher in inpatients or patients who had good PS, high bodyweight, high body mass index, or autoimmune diseases than in those without these characteristics. The post-marketing incidence of TRAEs with nivolumab in patients with MPM has been evaluated, and no new safety signals were identified compared to the phase II clinical trial in Japan.

Nivolumab as Second-Line Therapy Improves Survival in Patients with Unresectable Hepatocellular Carcinoma.

Limited data exists for the efficacy and outcomes of nivolumab as a second-line treatment for unresectable hepatocellular carcinoma (uHCC). We aimed to assess the efficacy and safety of nivolumab in patients with uHCC who experienced disease progression during sorafenib treatment. In this retrospective, observational, multicenter study, adult Child-Turcotte-Pugh A/7B patients with uHCC who tolerated sorafenib therapy but showed disease progression switched to second-line intravenous nivolumab (n = 42). A similar number of consecutive, unselected patients who were maintained on sorafenib therapy, regardless of tumoral response or progression, served as historical controls (n = 38). The primary endpoint was overall survival (OS, defined as the time from starting sorafenib in either group up to death due to any cause) and analyzed by intention-to-treat. The mean age of the overall cohort was 72.4 ± 10.1 years, of whom 87.5% were males and 58.8% had underlying viral etiology. Patients in the two cohorts were similar, except those who received nivolumab had more co-morbidities (70.0% vs. 15.4%), ECOG-2 status (21.4% vs. 15.8%), BCLC stage C (81.0% vs. 47.4%), and extravascular invasion (54.4% vs. 21.8%) (p < 0.05 for all). More patients in the nivolumab arm were Child-Turcotte-Pugh B (35.7% vs. 21.1%, p = 0.15). Median OS was 22.2 months (95% CI: 8.9-49.8) on second-line nivolumab and 11.0 months (95% CI: 3.6-18.4) on sorafenib alone (HR 1.93; 95% CI: 1.1-3.3, p = 0.014). Median OS after starting nivolumab was 10.2 months, and time-to-progression was 4.9 months (95% CI: 3.2-6.3). Nivolumab is an effective second-line treatment option in patients with uHCC who progress on sorafenib, with significantly improved OS. These early real-life data offer encouraging results, similar to those shown in Phase I/IIa clinical trials. Further investigations are warranted for the use of nivolumab as a monotherapy.

Adrenal Metastases Are Associated with Poor Outcomes in Patients with Metastatic Clear Cell Renal Cell Carcinoma Treated with Nivolumab in the GETUG-AFU-26 NIVOREN Phase 2 Trial

BackgroundGlandular metastases (GMs; adrenal gland, pancreas, thyroid, ovary, breast, or prostate) are rare in metastatic clear cell renal cell carcinoma (mccRCC). Previous studies have indicated that GM patients treated with antiangiogenic therapy experience significantly longer overall survival (OS). ObjectivesTo assess outcomes for mccRCC with or without GMs treated with nivolumab. Design, setting, and participantsThe GETUG-AFU-26 NIVOREN phase 2 trial evaluated the activity and safety of nivolumab in patients with mccRCC who experienced failure of antiangiogenic therapies (NCT03013335). In this ancillary study, patients were divided into two groups according to the presence or absence of at least one GM. Outcome measurements and statistical analysisThe primary outcome was OS; secondary outcomes were progression-free survival (PFS) and the objective response rate (ORR). Survival was estimated using the Kaplan-Meier method. Univariate and multivariable Cox regression models are used to estimate the hazard ratio (HR) with 95% confidence interval (CI) for survival outcomes. Subgroup analyses were performed for patients with pancreatic metastases and patients with adrenal metastases. Results and limitationsAmong 720 patients treated with nivolumab between February 2016 and July 2017, 217 had GMs, of whom 151/217 had adrenal metastases and 86/217 had pancreatic metastasis. Patients with adrenal metastases had worse 12-mo OS (64% vs 71.1%) and 6-mo PFS (27.2% vs 36.6%) and a lower objective response rate (12.5%, 95% CI 7.6%–19.0%, vs 23.2%, 95% CI 19.8–27.0%; p = 0.005) than patients without adrenal metastases. Conversely, univariate analysis showed that patients with pancreatic metastases had significantly better 12-mo OS (82.3% vs 67.9%; HR 0.59, 95% CI 0.40–0.85) in comparison to patients with nonpancreatic GMs. On multivariable analysis, only adrenal metastasis remained associated with adverse prognosis. ConclusionsAdrenal metastasis is an independent prognostic factor for poor response and survival in the GETUG-AFU-26 NIVOREN trial. Limited activity with nivolumab was observed for patients with mccRCC with adrenal metastases. These results warrant an evaluation of the prognostic value of adrenal metastases in patients treated with immunotherapy combinations with ipilimumab or tyrosine kinase inhibitors. Patient summaryOur study showed that metastasis in the adrenal glands could be an independent factor associated with poor response to immunotherapy and survival for patients with metastatic kidney cancer. It would be useful to evaluate the prognostic value of adrenal gland metastasis in patients treated with immunotherapy combinations or immunotherapy agents combined with drugs called tyrosine kinase inhibitors.

A phase II trial of nivolumab for patients with platinum-refractory recurrent or metastatic salivary gland cancer.

6092 Background: Salivary gland cancer is rare and has various pathological subtypes. With this rarity and heterogeneity, the therapeutic contribution of chemotherapy, including immune checkpoint inhibitors, for recurrent or metastatic salivary gland cancer (RM-SGC) has not been elucidated. The purpose of this trial was to investigate the efficacy and safety of nivolumab for patients with platinum-refractory RM-SGC. Methods: This open-label, single-arm, multicenter phase II trial was conducted at 9 centers in Japan. Eligible patients had platinum-refractory recurrent or metastatic salivary gland cancer with measurable lesions by RECIST v1.1 and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 1, or 2. Nivolumab 240 mg/body was administered intravenously every 2 weeks until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). We set the null hypothesis at 3% and the expected at 15% with a one-sided alfa of 0.1 and power of 80%. Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: Twenty-four patients (16 males; median age, 65.5 years [range, 34-78 years]) were enrolled between March 2018 and January 2022. Pathological types were salivary duct carcinoma (n = 10), adenoid cystic carcinoma (n = 6), adenocarcinoma not otherwise specified (n = 5), mucoepidermoid carcinoma (n = 2), and acinic cell carcinoma (n = 1). In the majority of cases the primary site was a major salivary gland (n = 21), namely the parotid gland in 16 patients and submandibular gland in 5. The primary endpoint of ORR was 8.3% (2/24, 80% CI, 2.2-20.6%), with 2 partial responses (PR) in patients with salivary duct carcinoma (2/10, ORR: 20.0%). DCR was 29.2% (7/24, 2 in PR and 5 in stable disease), and all of the other 17 patients（70.8%）showed progressive disease (PD) on first disease evaluation at 12 weeks. With a median follow up for survivors of 32.0 months, median PFS and OS were 3.0 months (95% CI, 2.8-3.2 months) and 25.0 months (95% CI, 10.9-39.1 months), respectively. There was no new safety concern with nivolumab monotherapy. Conclusions: This phase II trial of nivolumab monotherapy for patients with platinum-refractory RM-SGC did not meet its primary endpoint of ORR. Although nivolumab monotherapy may be worth further development in salivary duct carcinoma, these results may raise concerns over nivolumab monotherapy for RM-SGC. Translational research to elucidate the immune microenvironment of each pathological type is under investigation. Clinical trial information: UMIN000029636 .

Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: results from the EORTC-ETOP NIVOTHYM phase II trial

Thymic malignancies are rare intrathoracic tumors, which may be aggressive and difficult to treat. They represent a therapeutic challenge in the advanced/metastatic setting, with limited treatment options after the failure of first-line platinum-based chemotherapy. They are frequently associated with autoimmune disorders that also impact oncological management. NIVOTHYM is an international, multicenter, phase II, two-cohort, single-arm trial evaluating the activity and safety of nivolumab [240 mg intravenously (i.v.) q2 weeks] alone or with ipilimumab (1 mg /kg i.v. q6 weeks) in patients with advanced/relapsed type B3 thymoma or thymic carcinoma, after exposure to platinum-based chemotherapy. The primary endpoint is progression-free survival rate at 6 months (PFSR-6) based on RECIST 1.1 as per independent radiological review. From April 2018 to February 2020, 55 patients were enrolled in 15 centers from 5 countries. Ten patients (18%) had type B3 thymoma and 43 (78%) had thymic carcinoma. The majority were male (64%), and the median age was 58 years. Among the 49 eligible patients who started treatment, PFSR-6 by central review was 35% [95% confidence interval (CI) 22% to 50%]. The overall response rate and disease control rate were 12% (95% CI 5% to 25%) and 63% (95% CI 48% to 77%), respectively. Using the Kaplan-Meier method, median progression-free survival and overall survival by local assessment were 6.0 (95% CI 3.1-10.4) months and 21.3 (95% CI 11.6-not estimable) months, respectively. In the safety population of 54 patients, adverse events (AEs) of grade 1/2 were observed in 22 (41%) patients and grade 3/4 in 31 (57%) patients. Treatment-related AEs of grade 4 included one case of neutropenia, one case of immune-mediated transaminitis, and two cases of myocarditis. Nivolumab monotherapy demonstrated an acceptable safety profile and objective activity, although it has been insufficient to meet its primary objective. The second cohort of NIVOTHYM is currently ongoing to assess the combination of nivolumab plus ipilimumab.

Efficacy and safety of nivolumab in bone metastases from renal cell carcinoma: Results of the GETUG-AFU26-NIVOREN multicentre phase II study

IntroductionBone metastases (BM) in renal cell carcinoma (RCC) are associated with a poor prognosis based on retrospective studies evaluating antiangiogenic agents. Few data are available regarding immune checkpoint inhibitors (ICI) in patients with bone metastatic RCC. NIVOREN is a multicentre prospective study in which patients were treated with nivolumab after the failure of antiangiogenic agents. We aim to assess the impact of BM on prognosis, and the efficacy and safety of nivolumab in patients enrolled in the NIVOREN trial. Materials and methodsAll patients with BM at inclusion were included in our study. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), safety, and skeletal-related events (SRE). ResultsAmong 720 patients treated with nivolumab, 194 presented BM at inclusion. The median follow-up was 23.9 months. Median OS was 17.9 months in patients with BM versus 26.1 months in patients without BM (p = 0.0023). The difference was not statistically significant after adjustment (p = 0.0707). The median PFS was shorter in patients with BM even after adjustment (2.8 versus 4.6 months, p = 0.0045), as well as the ORR (14.8% versus 23.3%). SRE occurred for 36% of patients with BM. A post-hoc analysis evaluating the impact of bone-targeting agents (BTA) on SRE incidence showed a significant benefit of BTA on the incidence of SRE (OR = 0.367, CI95% [0.151–0.895]). ConclusionNivolumab is associated with shorter PFS, and lower ORR in RCC patients with BM. Our study suggests that BTA in association with immunotherapy decreases the incidence of SRE.

Efficacy and safety of nivolumab in renal cell carcinoma patients with BONE metastases: Results of the GETUG: AFU 26 nivoren multicenter phase II study.

342 Background: Bone metastases (BM) in renal cell carcinoma (RCC) are associated with a poor prognosis based on retrospective studies in which patients were treated with antiangiogenic agents. Since the development of immune checkpoint inhibitors, few data are available regarding the prognosis impact of BM or the efficacy and safety of checkpoint inhibitors in patients with bones metastatic RCC. GETUG-AFU26-NIVOREN (NIVOREN) is a French multicenter prospective study in which patients were treated with nivolumab after failure of one or more antiangiogenic tyrosine kinase inhibitors. We therefore aim to evaluate the impact of BM on prognosis, and the efficacy and safety of nivolumab in patients with BM enrolled in NIVOREN trial. Methods: All adult patients with BM at inclusion were included in our study. The primary endpoint of this ancillary study was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), safety, and skeletal-related events (SRE) in patients with BM. Clinical data were collected prospectively, except for SRE data which were collected retrospectively in a complementary consent report form. Results: Among 720 patients treated with nivolumab in the NIVOREN study, 194 had BM at inclusion. After a median follow-up of 23.9 months, the median OS was 17.9 months in patients with BM versus 26.1 months in patients without BM (HR = 1.42 CI95% [1.13-1.79], p = 0.0023). After adjustment on sex, age, IMDC group and line of treatments, the difference was not significant (HR = 1.24, CI95% [0.98-1.56], p = 0.0707). The median PFS was shorter in patients with BM even after adjustment (2.8 versus 4.6 months, HR = 1.30 CI95% [1.08-1.56]), as well as the ORR (14.8% versus 23.3%). The safety profile was similar between patients with or without BM at inclusion. The incidence of SRE in the BM population was 36% during the treatment period with nivolumab. A post-hoc analysis evaluating the impact of bone-targeting agents in association with nivolumab on SRE incidence was performed. There was a statistically significant benefit in patients treated with bone-targeting agents on the incidence of SRE (OR = 0.367, CI95% [0.151-0.895], p = 0.0276). Conclusions: Nivolumab is associated with shorter OS, PFS, and lower ORR in patients with BM. Our study confirms, in the era of immunotherapy that patients with BM are associated with poorer prognosis and suggests that association with bone-targeting agents decreases the incidence of SRE. Clinical trial information: 2015-004117-24.

Single-center prospective study on the efficacy of nivolumab against platinum-sensitive recurrent or metastatic head and neck squamous cell carcinoma

Nivolumab, an immune checkpoint inhibitor, is beneficial to patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). However, platinum-sensitive R/M-HNSCC has not yet been studied. Hence, in this prospective study, we evaluated the efficacy and safety of nivolumab in patients with platinum-sensitive R/M-HNSCC. This prospective single-arm study was conducted in a single institution in Japan. Patients with platinum-sensitive R/M-HNSCC (defined as head and neck cancer that recurred or metastasized at least 6 months after platinum-based chemotherapy or chemoradiotherapy) were enrolled. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), overall response rate (ORR), immune-related adverse events (irAEs), and quality of life (QOL). This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031324). Twenty-two patients with platinum-sensitive R/M-HNSCC were enrolled. The median OS was 17.4 months, and the 1-year OS rate was 73%. The median PFS was 9.6 months, 1-year PFS rate was 48%, and ORR was 36%. Sixteen irAEs were recorded in 12 patients; however, no grade 4 or 5 irAEs were observed. The QOL assessments revealed that nivolumab did not decrease the QOL of patients. Nivolumab is effective against platinum-sensitive R/M-HNSCC with acceptable safety.

Outcomes of long-term nivolumab and subsequent chemotherapy in Japanese patients with head and neck cancer: 2-year follow-up from a multicenter real-world study

BackgroundWe have previously reported the effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) in real-world clinical practice in Japan. Here, we report long-term outcomes from this study in the overall population and subgroups stratified by subsequent chemotherapy.MethodsIn this multicenter, retrospective observational study, Japanese patients with recurrent or metastatic (R/M) HNC receiving nivolumab were followed up for 2 years. Effectiveness endpoints included overall survival (OS), OS rate, progression-free survival (PFS), and PFS rate. Safety endpoints included the incidence of immune-related adverse events (irAEs).ResultsOverall, 256 patients received a median of 6.0 doses (range: 1–52) of nivolumab over a median duration of 72.5 days (range: 1–736). Median OS was 9.5 months [95% confidence interval (CI) 8.2–12.0] and median PFS was 2.1 months (95% CI 1.8–2.7). A significant difference between 2-year survivors (n = 62) and non-2-year survivors was observed by median age (P = 0.0227) and ECOG PS (P = 0.0001). Of 95 patients who received subsequent chemotherapy, 54.7% received paclitaxel ± cetuximab. The median OS and PFS from the start of paclitaxel ± cetuximab were 6.9 months (95% CI 5.9–11.9) and 3.5 months (95% CI 2.3–5.5), respectively. IrAEs were reported in 17.2% of patients. Endocrine (7.0%) and lung (4.3%) disorders were the most common irAEs; kidney disorder (n = 1) was newly identified in this follow-up analysis.ConclusionsResults demonstrated the long-term effectiveness of nivolumab and potential effectiveness of subsequent chemotherapy in patients with R/M HNC in the real-world setting. Safety was consistent with that over the 1-year follow-up.

Nivolumab in metastatic renal cell carcinoma: results from the Turkish Oncology Group Kidney Cancer Consortium database.

Aim: The authorspresentreal-world data on the efficacy and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Methods: The Turkish Oncology Group Kidney Cancer Consortium (TKCC)database includes patients with mRCC from 13 cancer centers in Turkey. Patients with mRCC treated with nivolumab in the second line and beyond were extracted from the TKCC database. Results: A total of 173 patients were included. The rates of patients treated with nivolumab in the second, third, fourthand fifth lines were 47.4%, 32.4%, 14.5%and 5.7%, respectively. The median overall survival and progression-free survival were 24.2months and 9.6months, respectively. Nivolumab was discontinued owing to adverse events in 11 (6.4%) patients. Conclusion: Nivolumab was effective in patients with mRCCand no new safety signal was observed.

Real-world safety of nivolumab in patients with non-small-cell lung cancer in Japan: Postmarketing surveillance.

Postmarketing surveillance of Japanese patients with unresectable, previously treated, advanced or recurrent non‐small‐cell lung cancer treated with nivolumab was undertaken during the conditional approval period. The study aim was to evaluate the occurrence of treatment‐related adverse events of nivolumab in the real world. Patients were registered between December 2015 and March 2016 at 536 sites. Nivolumab was given intravenously (3 mg/kg every 2 weeks); the observation period was 12 months after the first dose of nivolumab. Patients were evaluated for safety (n = 3601; 18.2% ≥75 years, 22.4% ECOG performance status ≥2) and effectiveness (n = 3570). The frequencies of any grade and grade 3 or higher treatment‐related adverse events were 47.1% and 15.9%, respectively. The most frequent treatment‐related adverse events (any grade) were interstitial lung disease (6.4%), hypothyroidism (5.7%), and diarrhea (4.4%). Treatment‐related adverse events of special interest (priority items) occurring at a frequency of 5% or more were adverse events related to interstitial lung disease, thyroid dysfunction, liver dysfunction, colitis/severe diarrhea, infusion reaction, and infusion reaction within 24 hours. Significant risk factors for these priority items were identified by competing risk analysis: interstitial lung disease (previous/comorbid interstitial lung disease, abnormal findings on chest imaging, and smoking history); liver dysfunction (previous/comorbid liver disease, smoking history, and metastasis); thyroid dysfunction (previous/comorbid thyroid disease and performance status); and colitis/severe diarrhea (treatment line 2 vs ≥3). The 12‐month survival rate was 40.7%. In conclusion, the safety profile of nivolumab in this postmarketing surveillance was similar to that in clinical trials, and no new safety signals were identified. The study was registered with the Japan Pharmaceutical Information Center (clinicaltrials.jp: Japic‐163271).

LBA66 Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: Results from the EORTC-ETOP NIVOTHYM phase II trial

Thymic malignancies are rare intrathoracic tumors which still represent a therapeutic challenge in the advanced/metastatic setting, with limited treatment options after the failure of platinum-based chemotherapy.

HL-398: Five-Year Overall Survival from the CheckMate 205 Study of Nivolumab for Relapsed or Refractory (R/R) Classical Hodgkin Lymphoma (cHL)

Context PD-1 immune checkpoint inhibitors, including nivolumab, have shown strong activity in patients with R/R cHL. The CheckMate 205 study demonstrated an objective response rate (ORR) of 69%, a median duration of response (DOR) of 17 months, and median progression-free survival (PFS) of 15 months, at a median follow-up of 18 months. Objective Assess the longer-term outcomes of CheckMate 205 with a median follow-up of 58 months. Design CheckMate 205 (NCT02181738) enrolled patients with R/R cHL after auto-HCT failure into three cohorts by treatment history: (A) brentuximab vedotin (BV)-naive, (B) BV after auto-HCT, and (C) BV before and/or after auto-HCT. Interventions Nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Patients in cohort C discontinued nivolumab after 1 year in complete remission (CR) with the option to resume within 2 years if relapsed. Outcome Measures Primary: ORR. Others: CR, DOR, PFS, overall survival (OS), and safety. Results Overall, 243 patients were treated. Median duration of treatment was 14 months. ORR was 71% (95% CI, 65%–77%), and CR rate was 21%. Median PFS was 15 months (95% CI, 11–19), and median DOR was 18 months (95% CI, 15–26). The 2-year and 5-year OS rates (95% CI) were 87% (82%–91%) and 71% (65%–77%), and PFS rates were 37% (30%–44%) and 18% (12%–25%), respectively. Patients with CR had improved OS; failure to achieve disease control was a poor prognostic factor for OS. Per protocol, 12 patients in cohort C stopped treatment after ≥1 year of CR. After median of 48 months (range, 36–55) from last treatment, 6 patients were still in response; 3 were re-treated with nivolumab after disease progression (2 re-achieved CR; 1 partial response). The safety profile is similar to previous reports, and no new toxicities were observed. There were no treatment-related deaths. Conclusions This 5-year analysis of CheckMate 205 demonstrated favorable OS and confirmed the efficacy and safety of nivolumab for patients with R/R cHL after auto-HCT. It appears feasible to stop nivolumab after 1 year of CR and re-initiate treatment upon disease progression. Funding BMS. Previous presentation ICML 2021 PD-1 immune checkpoint inhibitors, including nivolumab, have shown strong activity in patients with R/R cHL. The CheckMate 205 study demonstrated an objective response rate (ORR) of 69%, a median duration of response (DOR) of 17 months, and median progression-free survival (PFS) of 15 months, at a median follow-up of 18 months. Assess the longer-term outcomes of CheckMate 205 with a median follow-up of 58 months. CheckMate 205 (NCT02181738) enrolled patients with R/R cHL after auto-HCT failure into three cohorts by treatment history: (A) brentuximab vedotin (BV)-naive, (B) BV after auto-HCT, and (C) BV before and/or after auto-HCT. Nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Patients in cohort C discontinued nivolumab after 1 year in complete remission (CR) with the option to resume within 2 years if relapsed. Primary: ORR. Others: CR, DOR, PFS, overall survival (OS), and safety. Overall, 243 patients were treated. Median duration of treatment was 14 months. ORR was 71% (95% CI, 65%–77%), and CR rate was 21%. Median PFS was 15 months (95% CI, 11–19), and median DOR was 18 months (95% CI, 15–26). The 2-year and 5-year OS rates (95% CI) were 87% (82%–91%) and 71% (65%–77%), and PFS rates were 37% (30%–44%) and 18% (12%–25%), respectively. Patients with CR had improved OS; failure to achieve disease control was a poor prognostic factor for OS. Per protocol, 12 patients in cohort C stopped treatment after ≥1 year of CR. After median of 48 months (range, 36–55) from last treatment, 6 patients were still in response; 3 were re-treated with nivolumab after disease progression (2 re-achieved CR; 1 partial response). The safety profile is similar to previous reports, and no new toxicities were observed. There were no treatment-related deaths. This 5-year analysis of CheckMate 205 demonstrated favorable OS and confirmed the efficacy and safety of nivolumab for patients with R/R cHL after auto-HCT. It appears feasible to stop nivolumab after 1 year of CR and re-initiate treatment upon disease progression. BMS. ICML 2021

P1-5 Retrospective analysis of the efficacy and safety of nivolumab in patients with treatment-refractory esophageal cancer

In February 2020, nivolumab was approved for unresectable advanced or recurrent esophageal cancer in Japan. The importance of nivolumab for treatment-refractory esophageal cancer is rapidly increasing in clinical practice. We retrospectively evaluated the efficacy and safety of 9 patients who received nivolumab therapy for unresectable advanced or recurrent esophageal cancer from April 2017 to July 2020. Patients characteristics were as follows; all 9 patients were males and their median age was 69 years (range 51-80 years). 8 patients had a good (0 or 1) performance status (PS) and one patient had PS of 3 according to the Eastern Cooperative Oncology Group (ECOG) scale. 9 patients had squamous cell carcinoma. Common metastatic sites were lymph node (8 cases), liver (3 cases), and lung (3 cases). Among 9 patients, all patients were previously treated with fluorouracil and cisplatin and 2 patients were treated with paclitaxel. The median time to treatment failure (TTF) was 2 months (range 1-3). Out of 9 patients, no complete response and one patient had partial response. The response rate was 11% and disease control rate was 22%. Infusion reaction were observed in 2 patients. One patient developed liver injury during treatment. We retrospectively investigated the efficacy and toxicity of nivolumab in patients with treatment-refractory esophageal cancer at our hospital.

Effectiveness and safety of nivolumab in patients with advanced melanoma: A multicenter, observational study

This retrospective observational study aimed to determine the effectiveness, safety and patterns of the use of nivolumab in patients with advanced melanoma in real-world clinical practice in France using data from a Temporary Authorization for Use Program (ATU). Data were collected from patients with unresectable or metastatic melanoma enrolled in a French national database (Réseau pour la Recherche et l'Investigation Clinique sur le Mélanome: Ric-Mel) and treated with nivolumab during the ATU program (12 September 2014 to 31 August 2015). The primary objectives of the study were to evaluate the effect of patient characteristics on clinical response and overall survival (OS). Among 400 included patients (median age 66 years), the majority (83%) received nivolumab as second- or subsequent-line therapy. The median durations of progression-free survival and OS were 3.3 and 14.1 months, respectively, and 31.6% of patients achieved an objective response with a median duration of 20.1 months (range: 0-34.7). The safety profile of nivolumab was manageable and consistent with those of previous clinical trials, with an incidence of grade 3-5 adverse events of 13.8%. The safety and effectiveness of nivolumab in patients with advanced melanoma in real-world clinical practice in France were in line with the data reported in the Phase 3 trials CheckMate 066 and 037 of nivolumab in this patient population.

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

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 &gt; 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.

Effectiveness and safety of nivolumab in patients with head and neck cancer in Japanese real-world clinical practice: a multicenter retrospective clinical study

BackgroundTo fill the data gap between clinical trials and real-world settings, this study assessed the overall effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) during Japanese real-world clinical practice.MethodsThis was a multicenter, retrospective study in Japanese patients with recurrent or metastatic HNC who received nivolumab for the first time between July and December 2017. Data on the clinical use, effectiveness, and safety of nivolumab were extracted from patient medical records.ResultsOverall, 256 patients were enrolled in this study. The median duration of nivolumab treatment was 72.5 days, with patients receiving a median of 6.0 (range 1–27) doses. Median overall survival (OS) was 9.5 (95% confidence interval [CI] 8.2–12.0) months and the estimated 12-month OS rate was 43.2%. The objective response rate (ORR) was 15.7% overall and 21.1%, 7.1%, and 13.6% in patients with primary nasopharynx, maxillary sinus, and salivary gland tumors, respectively, who had been excluded from CheckMate 141. Grade ≥ 3 immune-related adverse events occurred in 5.9% of patients. No new safety signals were identified compared with adverse events noted in CheckMate 141.ConclusionsThe effectiveness and safety of nivolumab in real-world clinical practice are consistent with data from the CheckMate 141 clinical trial. Therapeutic response was also observed in the groups of patients excluded from CheckMate 141.Trial registration numberUMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436)

Nivolumab in Advanced Hepatocellular Carcinoma: Safety Profile and Select Treatment-Related Adverse Events From the CheckMate 040 Study.

BackgroundCheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment‐related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open‐label CheckMate 040 study.Materials and MethodsSelect TRAEs (sTRAEs; TRAEs with potential immunologic etiology requiring more frequent monitoring) occurring between first dose and 30 days after last dose were analyzed in patients in the dose‐escalation and ‐expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and the outcome of treatment with immune‐modulating medication (IMM) was evaluated.ResultsThe analysis included 262 patients. The most common sTRAE was skin (35.5%), followed by gastrointestinal (14.5%) and hepatic (14.1%) events; the majority were grade 1/2, with 10.7% of patients experiencing grade 3/4 events. One patient had grade 5 pneumonitis. Median (range) TTO ranged from 3.6 (0.1–59.9) weeks for skin sTRAEs to 47.6 (47.1–48.0) weeks for renal sTRAEs. Overall, 68% of sTRAEs resolved, with median (range) TTR ranging from 3.7 (0.1–123.3+) weeks for gastrointestinal sTRAEs to 28.4 (0.1–79.1) weeks for endocrine sTRAEs. Most gastrointestinal and all hepatic events resolved with treatment in accordance with established toxicity management algorithms. In 57 patients (40%), sTRAEs were managed with IMM. Reoccurrence of sTRAEs was uncommon following rechallenge with nivolumab.ConclusionNivolumab demonstrated a manageable safety profile in this analysis of patients with advanced HCC. A majority of sTRAEs resolved with treatment.Implications for PracticeNivolumab is a viable treatment option for patients with previously treated advanced hepatocellular carcinoma as it has demonstrated durable tumor responses and promising survival. Nivolumab has a manageable safety profile. The most common select treatment‐related adverse events (sTRAEs) in this analysis were skin related (35%). Gastrointestinal and hepatic sTRAEs were observed in approximately 14% of patients. The majority of sTRAEs resolved (68%). Safety events are easier to manage if addressed early. Patient education on signs and symptoms to watch out for and the importance of early reporting and consultation should be emphasized.

Age-based efficacy and safety of nivolumab for recurrent or metastatic head and neck squamous cell carcinoma: A multicenter retrospective study.

This study retrospectively investigated the efficacy and safety of nivolumab for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) classified using age <65 years as the cutoff. Overall, 88 patients with R/M HNSCC treated with nivolumab were classified into the young group (<65 years; n = 39) and elderly group (≥65 years; n = 49). Efficacy was evaluated using overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR). Safety was evaluated considering immune-related adverse events (irAEs). The median OS was 9.7 and 8.6 months in the young and elderly groups, respectively. The 1-year OS rate was 42.0% and 29.4% in the young and elderly groups, respectively. The median PFS was 3.0 and 4.2 months in the young and elderly groups, respectively. The 1-year PFS rate was 30.0% and 27.9% in the young and elderly groups, respectively. In the young group, the ORR was 10.3% and DCR was 33.3%. In the elderly group, the ORR was 18.4% and DCR was 53.1%. There were no significant differences in OS, PFS, ORR, and DCR (P = 0.36, 0.53, 0.29 and 0.06, respectively). Interstitial lung disease (ILD) as an irAE occurred in the young group at a significantly higher rate (20.5% vs 4.1%; P = 0.02). There were no significant differences in OS, PFS, ORR, and DCR between the young and elderly groups. DCR tended to be better in the elderly group (P = 0.06). ILD occurred at a significantly higher rate in the young group.

Real life safety and effectiveness of nivolumab in older patients with non-small cell lung cancer: Results from the Belgian compassionate use program

ObjectivesTo compare real life effectiveness and safety of nivolumab in patients with non-small cell lung cancer (NSCLC), according to age and Eastern Cooperative Group performance status (ECOG-PS). MethodsWe performed a retrospective analysis of patients treated with nivolumab for NSCLC within a Belgian compassionate use program from July 2015 until December 2016. Safety and effectiveness were compared between patients aged ≥70 years and < 70 years and between ECOG-PS 0/1 and ≥ 2. ResultsA total of 324 patients with NSCLC were included. There was no significant difference between older (≥70) and younger (<70 years) patients with regards to progression free survival (PFS) (4 months (95%CI 2.6;4.8) versus 3.7 months (95%CI 1;7), p = 0.483) and overall survival (OS) (9.3 months (95% CI 5.5;13.1 months) versus 8.4 months (95%CI 6.3; 10.5), p = 0,638). Patients with an ECOG-PS ≥2 had a significant lower median PFS and OS compared to patients with an ECOG-PS 0–1 (2.2 (95%CI 1.4; 2.9) versus 5.6 months (95%CI 4.1; 7.1), p = 0.001 and 3.4 (95%CI 2.3; 4.5) versus 11.1 months (95%CI 8.9; 13.2), p < 0.001 respectively).No significant difference in all grades or grade 3/4 adverse events (AEs) were observed between the different age groups (p = 0.526 and p = 0.603 respectively). Patients with an ECOG-PS 0/1 had significantly more all grades AEs (p = 0.009) but no difference in grade 3/4 AEs was observed (p = 0.406) compared to ECOG-PS ≥2. ConclusionThis real life retrospective study confirms that safety and effectiveness of nivolumab is similar between different age groups, but that effectiveness is driven by performance status.