DOMENICA 10 SETTEMBRE Immuno News Servizio a cura di Filippo de Marinis & Cesare Gridelli

1. DOMENICA 10 SETTEMBREImmuno NewsServizio a cura di Filippo de Marinis & Cesare Gridelli

2. Italian nivolumab expanded access programme: real-world results innon-squamous non-small cell lung cancer patientsF. Grossi

3. Background Nivolumab monotherapy has shown survival benefit in patients (pts) with different tumors, including melanoma, lung cancer, renal cell carcinoma and head and neck cancer. The experience of pts and physicians in routine clinical practice is often different from that in a controlled clinical trial setting. Here, we report efficacy and safety of nivolumab monotherapy in pts with non-squamous non-small cell lung cancer (NSCLC) treated in the nivolumab Expanded Access Programme in Italy. Methods Nivolumab was available upon physician request for pts aged ≥18 years who had relapsed after a minimum of one prior systemic treatment for stage IIIB/stage IV non-Squamous NSCLC. Nivolumab 3 mg/kg was administered intravenously every 2 weeks to a maximum of 24 months. Pts included in the analysis had received at least 1 dose of nivolumab and were monitored for adverse events (AE) using Common Terminology Criteria for Adverse Events. Results In total, 1588 Italian pts participated in the EAP across 168 centers. Baseline characteristics of pts were representative of the population with non-squamous NSCLC, in the advanced disease setting. With a median follow-up of 7.8 months (1-21.9) and a median of 7 doses, the overall response rate (ORR) was 18%, including 10 pts (<1%) with complete response and 280 pts (17%) with partial response. Stable disease has been defined for 414 pts (26%) and totally 279 patients were treated beyond progression. As of March 2017, median overall survival (OS) was 11 months (range: 10.0-12.0). Response rates and survival were comparable among pts regardless age (< and ≥ 75 years), presence of brain metastasis and number of prior therapies. Overall, among 1588 pts, 1254 discontinued treatment for any reason, with only 80 pts (5%) who discontinued treatment due to related adverse events. Conclusions To date, this is the largest clinical experience with nivolumab in a real-world setting. These preliminary EAP data confirm that nivolumab seems to be an effective and safe therapy for pre-treated patients with non-squamous NCSLC, supporting its use in current clinical practice.

10. Three-year follow-up from CheckMate 017/057: Nivolumab versus docetaxel in patients with previously treated advanced non-small cell lung cancer (NSCLC)E. Felip

11. Background Long-term data comparing outcomes with immune checkpoint inhibitors versus chemotherapy in NSCLC are limited. The phase 3 trials CheckMate 017 and 057 demonstrated improved overall survival (OS), objective response rates (ORR), and quality of life, as well as a favorable safety profile, with the anti-programmed death (PD)-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous and non-squamous NSCLC, respectively. Updated results based on a minimum follow-up of 3 y are reported. Methods Patients were randomized 1:1 to receive nivolumab 3 mg/kg Q2W (with option to change to 480 mg Q4W after Sep 2016) or docetaxel 75 mg/m2 Q3W until progression or discontinuation. After completion of the primary analyses, patients who ended treatment with docetaxel could cross over to receive nivolumab. The primary endpoint of each study was OS; other endpoints were ORR, progression-free survival, and efficacy by PD ligand1 (PD-L1) expression. Results After a minimum follow-up of 36.6 mo in each study (Feb 2017 database locks), 6% of the 427 total patients randomized to the 2 nivolumab arms remained on treatment; no patients remained on docetaxel. Nivolumab continued to show an OS benefit versus docetaxel, with 3-y OS rates of 16% versus 6% in CheckMate 017 and 18% versus 9% in CheckMate 057. Similar to prior reports, an OS benefit was observed in squamous NSCLC regardless of PD-L1 expression, and in non-squamous NSCLC was enhanced at higher PD-L1 expression levels (Table). Of 427 patients in the combined nivolumab arms, 71 (17%) had OS ≥ 3 y. Additional 3-y data across trial endpoints will be presented.Table: 1301PD OSa overall and by PD-L1 CheckMate 017 CheckMate 057 expression level (squamous NSCLC) (non-squamous NSCLC) NivolumabDocetaxel HR (95%CI) NivolumabDocetaxel HR (95%CI) Overall, n 135 137 – 292 290 – 3-y OS rate, % 16 6 0.62 18 9 0,74 (0.48, (0,62, 0.80) 0.89) PD-L1 <1%, n 54 52 – 108 101 – 3-y OS rate, % 13 4 0.60 11 8 0,91 (0.40, (0.68, 0.90) 1.21) PD-L1 ≥1%, n 63 56 – 123 123 – 3-y OS rate, % 14 9 0.74 26 10 0,58 (0.50, (0.44, 1.09) 0.76) PD-L1 ≥50%, n 17 10 – 66 46 – 3-y OS rate, % 29 20 0.68 39 9 0.35 (0.27, (0.22, 1.66) 0.55) a Kaplan-MeierestimatesCI = confidenceinterval; HR = hazardratio Conclusions With ≥3 y of follow-up from 2 randomized phase 3 studies, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced squamous and non-squamous NSCLC. Overall, 3-y survival was achieved in 17% of nivolumab-treated patients.