Safety and Efficacy of Nivolumab in Patients With Advanced Non-small-cell Lung Cancer Treated Beyond Progression.

Treatment with immune checkpoint inhibitors beyond progression is associated with improved survival in patients with melanoma and clear-cell renal carcinoma. Whether this association exists for patients with non-small-cell lung cancer (NSCLC) is currently still unclear. We performed a multi-institutional retrospective study based on landmark and multivariable analyses to evaluate the safety and efficacy of treatment with nivolumab beyond Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 progression in patients with advanced NSCLC. Criteria for receiving nivolumab beyond progression were investigator-assessed clinical benefit, stable performance status, tolerance of treatment, and no need of immediate intervention to prevent serious complication of progression. Of 176 patients progressed to nivolumab according to RECIST v1.1, 60 (34.1%) were treated beyond progression (TBP) and 116 (65.9%) were not-TBP (NTBP). The median overall survival was significantly longer in the TBP group compared with the NTBP group (17.8 vs. 3.7 months; hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.21-0.46; P < .0001). In a landmark analysis of evaluable patients beginning 6 weeks from first progression, the median overall survival for patients TBP was 10.7 months and for those NTBP, 3.4 months (HR, 0.48; 95% CI, 0.30-0.77; P = .002). Discontinuation of nivolumab at first progression was associated with shorter survival in multivariable analysis (HR, 2.98; 95% CI, 1.95-4.54; P < .001). No safety concerns emerged in patients who were in the TBP group. A subset of patients with NSCLC and progressive disease may continue to benefit from nivolumab beyond progression. Discontinuation of immunotherapy based only on RECIST v1.1 may be premature.

Ricciuti B ，Genova C ，Bassanelli M ，De Giglio A ，Brambilla M ，Metro G ，Baglivo S ，Dal Bello MG ，Ceribelli A ，Grossi F ，Chiari R ... -  《-》

Nivolumab treatment beyond progressive disease in advanced non-small cell lung cancer.

Enomoto T ，Tamiya A ，Matsumoto K ，Adachi Y ，Azuma K ，Inagaki Y ，Kouno S ，Taniguchi Y ，Saijo N ，Okishio K ，Atagi S ... -  《-》

Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025.

Response patterns to nivolumab differ from those seen with other approved targeted therapies. To investigate the efficacy of nivolumab in previously treated patients with advanced renal cell carcinoma who were treated beyond (Response Evaluation Criteria In Solid Tumors) RECIST progression. This was a subgroup analysis of patients treated with nivolumab in the phase 3 CheckMate 025 study. Patients continuing to tolerate therapy and exhibiting investigator-assessed clinical benefit were eligible to be treated beyond RECIST progression (TBP) and received therapy for ≥4 wk after first progression; patients not treated beyond RECIST progression (NTBP) received 0 wk to <4 wk of therapy after progression. Nivolumab 3mg/kg intravenously every 2 wk. Of 406 nivolumab-treated patients, 316 (78%) progressed by RECIST criteria. Of those who progressed, 48% were TBP, 52% were NTBP. Before being TBP, objective response rate (95% confidence interval) was 20% (14-28) and 14% (9-21) in patients TBP and NTBP, respectively. Differences in clinical characteristics assessed at first progression between patients TBP versus NTBP included better Karnofsky performance status, less deterioration in Karnofsky performance status, shorter time to response, lower incidence of new bone lesions, and improved quality of life. Postprogression, 13% of all patients TBP (20/153) had ≥30% tumor burden reduction including patients with preprogression and postprogression tumor measurements (n=142) and complete/partial response (28%, 8/29), stable disease (6%, 3/47), and progressive disease (14%, 9/66) as their best response before being TBP. Incidence of treatment-related adverse events in patients TBP was lower after (59%) versus before (71%) progression. Limitations included potential bias from the nonrandomized nature of the analysis. A subset of patients with advanced renal cell carcinoma and RECIST progression experienced tumor reduction postprogression with nivolumab, and had an acceptable safety profile. Clinical judgment remains essential when switching therapy. ClinicalTrials.gov Identifier: NCT01668784. A subset of patients with advanced renal cell carcinoma and disease progression may continue to benefit from nivolumab treatment beyond progression as evidenced by tumor reduction postprogression and an acceptable safety profile.

Escudier B ，Motzer RJ ，Sharma P ，Wagstaff J ，Plimack ER ，Hammers HJ ，Donskov F ，Gurney H ，Sosman JA ，Zalewski PG ，Harmenberg U ，McDermott DF ，Choueiri TK ，Richardet M ，Tomita Y ，Ravaud A ，Doan J ，Zhao H ，Hardy H ，George S ... -  《-》

Nivolumab treatment beyond RECIST-defined progression in recurrent or metastatic squamous cell carcinoma of the head and neck in CheckMate 141: A subgroup analysis of a randomized phase 3 clinical trial.

Response patterns with immune checkpoint inhibitors may be different from those with chemotherapy. Therefore, assessment of response to immunotherapy with the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, could result in premature treatment termination. The randomized, open-label, phase 3 CheckMate 141 trial (NCT02105636), which evaluated nivolumab in recurrent/metastatic squamous cell carcinoma of the head and neck after platinum therapy, allowed treatment beyond first RECIST-defined progression (TBP) according to protocol-specified criteria. In CheckMate 141, patients with RECIST-defined progression who had a stable performance status and demonstrated clinical benefit without rapid disease progression were permitted to receive TBP with nivolumab at 3 mg/kg every 2 weeks until further progression, which was defined as an additional ≥10% increase in tumor volume. This post hoc analysis evaluated outcomes for patients who received TBP with nivolumab. Of 240 patients randomized to nivolumab, 146 experienced RECIST-defined progression. Sixty-two of these patients received TBP, and 84 discontinued treatment (no TBP). Among the 60 TBP patients evaluable for response, 15 (25%) had no change in their tumor burden, and 15 (25%) had reductions in target lesion size; 3 patients (5%) had reductions >30%. The median overall survival among TBP patients was 12.7 months (95% confidence interval, 9.7-14.6 months). No new safety signals were observed with TBP. Exploratory analyses of immune cell biomarkers suggested a potential relationship with initial and TBP responses. Tumor burden reduction was noted in a proportion of patients who received TBP with nivolumab in CheckMate 141. Additional research is warranted to identify factors predictive of a TBP benefit in this population.

Haddad R ，Concha-Benavente F ，Blumenschein G Jr ，Fayette J ，Guigay J ，Colevas AD ，Licitra L ，Kasper S ，Vokes EE ，Worden F ，Saba NF ，Tahara M ，Jayaprakash V ，Lynch M ，Li L ，Gillison ML ，Harrington KJ ，Ferris RL ... -  《-》

Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: long-term outcomes from a multi-institutional analysis.

Ricciuti B ，Genova C ，De Giglio A ，Bassanelli M ，Dal Bello MG ，Metro G ，Brambilla M ，Baglivo S ，Grossi F ，Chiari R ... -  《-》