The advent of immune checkpoint‐inhibitors (CPI) has transformed treatment for several cancer types. This review was performed to assess the rate of adverse events (AEs) associated with the use of CPI, alone or in combinations. A review of AEs reporting quality was also performed. All publications of Randomized Clinical Trials (RCTs) assessing CPI published before December 2017 were included. To investigate the quality of AEs reporting, a set of items was defined based on the 2004 CONSORT harms extension statement. Rates of Grade 5, serious, and study‐withdrawal related AEs were collected in each treatment category. Specific immune related AEs (irAEs) were also collected when available. Pooled estimates of adverse event rates were calculated by using generalized linear mixed model. A total of 35 RCTs including 16,485 patients were included. The overall quality of AEs reporting was satisfactory, but items pertaining to methods of data collection and analysis were infrequently reported. Grade ≥ 3 AEs were reported for 14% (95% CI 12–16) of patients treated with PD(L)‐1 inhibitors, 34% (95% CI 27–42) of patients treated with CTLA‐4 inhibitors, 55% (95% CI 51–59) of patients on CPI combinations and 46% (95% CI 40–53) of patients on immunotherapy‐chemotherapy combination. The profile of irAEs was different among the treatment categories. The use of CPI, especially in combination, is associated with significant rates of Grade ≥ 3 AEs. Healthcare planning should anticipate the expected high number of patients presenting with irAEs in the future.

Background Advanced sarcoma is a group of heterogeneous disease with poor prognosis and poor efficacy of medical treatment. They represent a promising group of tumors to assess molecular-based therapy (MBT) strategy. Patients and methods Genomic profiles of patients with advanced sarcoma included in the ProfiLER program were established by NGS using a 69 genes panel and CGH array. A weekly molecular board reviewed genomic reports to select relevant genomic alterations and propose recommendations for MBT. Results A genomic profile was available for 158 of 164 patients. At least 1 relevant genomic alteration was reported for 106 patients (67%), with frequent multiple alterations (68%). In total, 289 relevant genomic alterations were identified in 143 different genes; 139 homozygous deletions, 86 gene amplifications and 64 somatic mutations. The most frequently impacted genes were TP53, Rb1, CDKN2A, CDK4, MDM2, and PTEN. MBT was recommended for 47 patients and initiated for 13 patients. One objective response was observed for an angiosarcoma treated with pazopanib for FLT4 amplification; 4 patients had a stable disease, including a long-lasting 33 months stabilization. Conclusion Genomic profiling for advanced sarcoma is feasible, even for bone sarcoma. A small proportion of patients are eventually treated with MBT, similar to other tumor types. We could not demonstrate this strategy to be beneficial to patients. Our data suggest that molecular profiling should not be used in routine practice but warrants further exploration in clinical trials, focusing on sarcoma with complex genomic, and adding transcriptomic analysis to the copy number and mutational analyses.

e16054 Background: TGCT are the most frequent cancers in men aged 15-45. This population is increasingly exposed to CA that is illegal in France. Its consequences on treatment and prognosis remain unknown. Methods: The use and the quantity of CA were evaluated for all pts treated by C for a TGCT in the CLB from 01/2016 to 06/2018. Tobacco (T) and alcohol (A) co-addictions were also analyzed. All pts had before starting C pulmonary test with diffusing capacity of the lung for carbon monoxyde (DLCO) evaluation. We searched a link between the use of toxics, contraindication to Bleomycin (B) due to decreased DLCO and tumor characteristics: stage and IGCCCG prognostic groups. Results: One hundred and thirty two pts with a median age of 33.5 years (interval: 17-65) received C for TGCT mainly for NSGCT (n = 97, 73%). Nine pts (7%) were treated in the adjuvant setting (1: 6 or 2 BEP: 3). In metastatic pts, 79 (60%), 30 (23%) and 14 (10%) were considered as good, intermediate and poor prognosis (PG) according to IGCCCG respectively. BEP was given for 3 cycles to 63 pts and 4 to29 and 6 pts received a dose dense regimen according to GETUG13. Eleven pts didn’t received B (5: 4EP, 6: 4VIP) because of DLCO alteration before the beginning of C. Eleven pts treated with B switched to a regimen without B due to a decrease of the DLCO during treatment. CA use was frequent (n = 20, 15%) with 8 pts (6%) having a regular CA consumption (median 5 joints/d). Seventy eight pts (59%) were regular T smokers. Co-addictions for CA consumers were frequent (90% for T and 50% for A). T and CA smokers had more DLCO alteration leading to B contraindication (p = 0.01 and p = 0.04). A quarter (n = 5) of pts using CA didn’t received B, and only 1 pt who didn’t receive B was not a smoker (T and CA). The use of CA was associated with PG, OR 5.46 (CI 95%: 1.35-21.2; p = 008). We could not observe a relationship between relapse and the use of CA (p = 0.34) because of the small number of relapses (n = 8). Half (n = 10) of CA consumers were single men and 25% (n = 5) were unemployed. Conclusions: The use of CA is significantly associated with PG and with a reduction of B use due to adecreased DLCO. The impact of CA intoxication is negative on the quality of treatment (because of more contraindications to B). The association with PG remains unclear, but may be related to social isolation.