375O - Final efficacy results from IMpower132: First-line atezolizumab + chemotherapy in patients with stage IV non-squamous NSCLC

Background The Phase III IMpower132 study, evaluating first line pemetrexed plus carboplatin/cisplatin with or without atezolizumab in Stage IV non-squamous NSCLC without EGFR or ALK driver mutations, has met its PFS endpoint with an HR of 0.60 (95% CI: 0.49, 0.72; P \u3c 0.0001; Papadimitrakopoulou, WCLC 2018). Here we present the final OS and safety results. Methods Patients were randomised 1:1 to 4 or 6 cycles of carboplatin AUC 6 mg/mL/min or cisplatin 75 mg/m2 + pemetrexed 500 mg/m2 Q3W alone (arm PP) or with atezolizumab 1200 mg Q3W (arm APP), followed by pemetrexed (PP) or atezolizumab + pemetrexed (APP) maintenance. Investigator-assessed PFS and OS were co-primary endpoints. Efficacy by PD-L1 status was an exploratory endpoint. Results At data cutoff (18 July 2019), 292 patients in arm APP and 286 patients in arm PP had a median follow-up of 28.4 mo. Updated median PFS was 7.7 months (APP) vs 5.2 months (PP); HR, 0.56 (95% CI: 0.47, 0.67). Final OS data are in the table. 38.7% (APP) vs 57.3% (PP) of patients received subsequent anti-cancer therapy, including immunotherapy in 5.5% vs 45.8%. Grade ≥ 3 treatment-related adverse events (AEs) occurred in 58.4% (APP) vs 43.1% (PP) of patients, including immune-mediated AEs in 6.9% (APP) vs 4.7% (PP) of patients. Table: 375O APP PP ITT n = 292 n = 286 mOS (95% CI), mo 17.5 (13.2, 19.6) 13.6 (11.0, 15.7) HRa (95% CI; P value) 0.86 (0.71, 1.06; P = 0.155) 12-Month OS 59.7% 55.0% 24-Month OS 39.1% 34.0% PD-L1–highb n = 25 n = 20 mOS (95% CI), mo NE (22.4, NE) 26.9 (4.7, NE) HR (95% CI) 0.73 (0.31, 1.73) PD-L1–lowb n = 63 n = 73 mOS (95% CI), mo 12.7 (8.7, 18.2) 16.2 (9.6, 22.6) HR (95% CI) 1.18 (0.80, 1.76) PD-L1–negativeb n = 88 n = 75 mOS (95% CI), mo 15.9 (11.6, 22.6) 10.5 (8.1, 13.5) HR (95% CI) 0.67 (0.46, 0.96) NE, not estimable. a Stratified. b PD-L1 status available in 60% of pts. PD-L1–high: ≥ 50% TC or ≥ 10% IC; PD-L1–low: ≥ 1% and \u3c 50% TC or ≥ 1% and \u3c 10% IC; PD-L1–negative: \u3c 1% TC and \u3c 1% IC. . Conclusions IMpower132 had met its co-primary PFS endpoint at the primary analysis but did not meet its co-primary OS endpoint in this final analysis. Atezolizumab + carboplatin/cisplatin + pemetrexed was well tolerated, and no new safety signals were identified. Clinical trial identification NCT02657434

Patterns of care and outcomes of 417 patients with METAstatic SYNovial sarcoma (METASYN): real-life data from the French Sarcoma Group (FSG)

International audienceBackground: Synovial sarcoma (SS) occurs in both adult and pediatric patients. The primary aim of this study is to describe the outcomes, prognostic factors, and treatment of patients with metastatic SS within a nationwide cohort.Patients and methods: All pediatric and adult patients with metastatic SS are registered in the French Sarcoma Group database. Data were collected from the national database https://conticabase.sarcomabcb.org/ up to March 2020. Descriptive and comparative analyses were conducted using SAS 9.4 and Stata Special Edition 16.1 software.Results: Between January 1981 and December 2019, 417 patients with metastatic SS from 17 French sarcoma centers were included, including 64 (15.3%) under the age of 26 years. Median age was 42.5 years (range 9-87 years). The metastases were synchronous (cohort 1) or metachronous (cohort 2) in 18.9% (N = 79) and 81.1% (N = 338) patients, respectively. Median overall survival (OS) from the date of metastasis was 22.3 months (95% confidence interval 19.7-24.1 months). First-line chemotherapy without ifosfamide and/or doxorubicin was unfavorable for progression-free survival and OS (P 12 months, local therapy, and ifosfamide in the first metastatic line were independent favorable prognostic factors.Conclusions: The outcome of patients with metastatic SS is influenced by local treatment, management in reference centers, and cytotoxic treatments given in the perioperative and metastatic setting

Prediction of local and metastatic recurrence in solitary fibrous tumor: construction of a risk calculator in a multicenter cohort from the French Sarcoma Group (FSG) database.

Solitary fibrous tumors (SFT) are rare unusual ubiquitous soft tissue tumors that are presumed to be of fibroblastic differentiation. At present, the challenge is to establish accurate prognostic factors. A total of 214 consecutive patients with SFT diagnosed in 24 participating cancer centers were entered into the European database (www.conticabase.org) to perform univariate and multivariate analysis for overall survival (OS), local recurrence incidence (LRI) and metastatic recurrence incidence (MRI) by taking competing risks into account. A prognostic model was constructed for LRI and MRI. Internal and external validations of the prognostic models were carried out. An individual risk calculator was carried out to quantify the risk of both local and metastatic recurrence. We restricted our analysis to 162 patients with local disease. Twenty patients (12.3%) were deceased at the time of analysis and the median OS was not reached. The LRI rates at 10 and 20 years were 19.2% and 38.6%, respectively. The MRI rates at 10 and 20 years were 31.4% and 49.8%, respectively. Multivariate analysis retained age and mitotic count tended to significance for predicting OS. The factors influencing LRI were viscera localization, radiotherapy and age. Mitotic count, tumor localization other than limb and age had independent values for MRI. Three prognostic groups for OS were defined based on the number of unfavorable prognostic factors and calculations were carried out to predict the risk of local and metastatic recurrence for individual patients. LRI and MRI rates increased between 10 and 20 years so relapses were delayed, suggesting that long-term monitoring is useful. This study also shows that different prognostic SFT sub-groups could benefit from different therapeutic strategies and that use of a survival calculator could become standard practice in SFTs to individualize treatment based on the clinical situation

Management and outcomes of adolescent and young adult sarcoma patients: results from the French nationwide database NETSARC.

International audienceBackgroundThe initial management of patients with sarcoma is a critical issue. We used the nationwide French National Cancer Institute-funded prospective sarcoma database NETSARC to report the management and oncologic outcomes in adolescents and young adults (AYAs) patients with sarcoma at the national level.Patients and methodsNETSARC database gathers regularly monitored and updated data from patients with sarcoma. NETSARC was queried for patients (15–30 years) with sarcoma diagnosed from 2010 to 2017 for whom tumor resection had been performed. We reported management, locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) in AYA treated in French reference sarcoma centers (RSC) and outside RSC (non-RSC) and conducted multivariable survival analyses adjusted for classical prognostic factors.ResultsAmong 3,227 patients aged 15–30 years with sarcoma diagnosed between 2010 and 2017, the study included 2,227 patients with surgery data available, among whom 1,290 AYAs had been operated in RSC, and 937 AYAs in non-RSC. Significant differences in compliance to guidelines were observed including pre-treatment biopsy (RSC: 85.9%; non-RSC 48.1%), pre-treatment imaging (RSC: 86.8%; non-RSC: 56.5%) and R0 margins (RSC 57.6%; non-RSC: 20.2%) (p < 0.001). 3y-OS rates were 81.1% (95%CI 78.3–83.6) in AYA in RSC and 82.7% (95%CI 79.4–85.5) in AYA in non-RSC, respectively. Whereas no significant differences in OS was observed in AYAs treated in RSC and in non-RSC, LRFS and PFS were improved in AYAs treated in RSC compared to AYAs treated in non-RSC (Hazard Ratios (HR): 0.58 and 0.83, respectively).ConclusionsThis study highlights the importance for AYA patients with sarcoma to be managed in national sarcoma reference centers involving multidisciplinary medical teams with paediatric and adult oncologists

Improved nationwide survival of sarcoma patients with a network of reference centers

International audienceBackground: We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since 2010.Patients and methods: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients' characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020.Results: A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n = 9266 before 2013, n = 12 274 between 2013 and 2015, n = 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients &gt;18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P &lt; 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P &lt; 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers.Conclusions: The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved

Neoadjuvant chemotherapy in high-risk soft tissue sarcomas: A Sarculator-based risk stratification analysis of the ISG-STS 1001 randomized trial

none79Background: The value of neoadjuvant chemotherapy in soft tissue sarcoma (STS) is not completely understood. This study investigated the benefit of neoadjuvant chemotherapy according to prognostic stratification based on the Sarculator nomogram for STS. Methods: This study analyzed data from ISG-STS 1001, a randomized study that tested 3 cycles of neoadjuvant anthracycline plus ifosfamide (AI) or histology-tailored (HT) chemotherapy in adult patients with STS. The 10-year predicted overall survival (pr-OS) was estimated with the Sarculator and was stratified into higher (10-year pr-OS .99). In lower risk patients, the 3- and 5-year Sarculator-predicted and study-observed OS rates were 0.85 and 0.80, respectively, and 0.89 and 0.82, respectively, in the AI arm (P =.507); the corresponding figures in the HT arm were 0.87 and 0.81, respectively, and 0.86 and 0.74, respectively (P =.105). Conclusions: High-risk patients treated with AI performed better than predicted, and this adds to the evidence for the efficacy of neoadjuvant AI in STS. Lay Summary: People affected by soft tissue sarcomas of the extremities and trunk wall are at some risk of developing metastasis after surgery. Preoperative or postoperative chemotherapy has been tested in clinical trials to reduce the chances of distant metastasis. However, study findings have not been conclusive. This study stratified the risk of metastasis for people affected by sarcomas who were included in a clinical trial testing neoadjuvant chemotherapy. Exploiting the prognostic nomogram Sarculator, it found a benefit for chemotherapy when the predicted risk, based on patient and tumor characteristics, was high.nonePasquali S.; Palmerini E.; Quagliuolo V.; Martin-Broto J.; Lopez-Pousa A.; Grignani G.; Brunello A.; Blay J.-Y.; Tendero O.; Diaz-Beveridge R.; Ferraresi V.; Lugowska I.; Infante G.; Braglia L.; Merlo D.F.; Fontana V.; Marchesi E.; Donati D.M.; Palassini E.; Bianchi G.; Marrari A.; Morosi C.; Stacchiotti S.; Bague S.; Coindre J.M.; Dei Tos A.P.; Picci P.; Bruzzi P.; Miceli R.; Casali P.G.; Gronchi A.; Dani C.; Villa C.; Messina A.; Rusi L.; Nuzzo A.M.; Nuzzo C.; De Paoli A.; Buonadonna A.; Comandone A.; Boglione A.; Livi L.; Greto D.; Riva N.; Monti M.; Pennacchioli E.; De Pas T.; Ippolito V.; Ledesma P.; Redondo A.; Valverde C.; Bratos R.; Cruz J.; Martinez Trufero J.; Cubedo R.; Sevilla I.; Luna P.; Lopez R.; Sancho P.; Bally O.; Brahmi M.; Ray-Coquard I.; Cassier P.; Marques N.; Tassy L.; Boudou-Rouquette P.; Tlemsani C.; Alexandre J.; Goldwasser F.; Bompas E.; Rolland F.; Perrin C.; Talarmin M.; Italiano A.; Toulmonde M.; Laramas M.; Bay J.-O.; Dubray-Longeras P.; Rutkowski P.Pasquali, S.; Palmerini, E.; Quagliuolo, V.; Martin-Broto, J.; Lopez-Pousa, A.; Grignani, G.; Brunello, A.; Blay, J. -Y.; Tendero, O.; Diaz-Beveridge, R.; Ferraresi, V.; Lugowska, I.; Infante, G.; Braglia, L.; Merlo, D. F.; Fontana, V.; Marchesi, E.; Donati, D. M.; Palassini, E.; Bianchi, G.; Marrari, A.; Morosi, C.; Stacchiotti, S.; Bague, S.; Coindre, J. M.; Dei Tos, A. P.; Picci, P.; Bruzzi, P.; Miceli, R.; Casali, P. G.; Gronchi, A.; Dani, C.; Villa, C.; Messina, A.; Rusi, L.; Nuzzo, A. M.; Nuzzo, C.; De Paoli, A.; Buonadonna, A.; Comandone, A.; Boglione, A.; Livi, L.; Greto, D.; Riva, N.; Monti, M.; Pennacchioli, E.; De Pas, T.; Ippolito, V.; Ledesma, P.; Redondo, A.; Valverde, C.; Bratos, R.; Cruz, J.; Martinez Trufero, J.; Cubedo, R.; Sevilla, I.; Luna, P.; Lopez, R.; Sancho, P.; Bally, O.; Brahmi, M.; Ray-Coquard, I.; Cassier, P.; Marques, N.; Tassy, L.; Boudou-Rouquette, P.; Tlemsani, C.; Alexandre, J.; Goldwasser, F.; Bompas, E.; Rolland, F.; Perrin, C.; Talarmin, M.; Italiano, A.; Toulmonde, M.; Laramas, M.; Bay, J. -O.; Dubray-Longeras, P.; Rutkowski, P