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Essentials Intracranial hemorrhage (ICH) is common in patients with brain tumors. We compared rates of ICH with DOACs and low molecular weight heparin. DOACs were associated with a lower incidence of ICH in primary brain tumors. DOACs appear safe to administer to patients with brain tumors. SUMMARY: Background Direct oral anticoagulants (DOACs) are efficacious in the treatment of cancer-associated thrombosis but are associated with an increased risk of hemorrhage compared with low-molecular-weight heparin in certain malignancies. Whether the DOACs increase the incidence of intracranial hemorrhage (ICH) in patients with brain tumors is not established. Objectives To determine the cumulative incidence of ICH in DOACs compared with Low-molecular-weight heparin (LMWH) in patients with brain tumors and venous thromboembolism. Patients and methods A retrospective comparative cohort study was performed. Radiographic images for all ICH events were reviewed and the primary endpoint was cumulative incidence of ICH at 12 months following initiation of anticoagulation. Results and conclusions A total of 172 patients with brain tumors were evaluated (42 DOAC and 131 LMWH). In the primary brain tumor cohort (n = 67), the cumulative incidence of any ICH was 0% in patients receiving DOACs vs. 36.8% (95% confidence interval [CI], 22.3-51.3%) in those treated with LMWH, with a major ICH incidence of 18.2% (95% CI, 8.4-31.0). In the brain metastases cohort (n = 105), DOACs did not increase the risk of any ICH relative to enoxaparin, with an incidence of 27.8% (95% CI, 5.5-56.7%) compared with 52.9% (95% CI, 37.4-66.2%). Similarly, DOAC did not increase the incidence of major ICH in brain metastases, with a cumulative incidence 11.1% (95% CI, 0.5-40.6%) vs. 17.8% (95% CI, 10.2-27.2%). We conclude that DOACs are not associated with an increased incidence of ICH relative to LMWH in patients with brain metastases or primary brain tumors.

To compare healthcare resource utilization (HRU) and costs associated with dose-dense methotrexate, vinblastine, doxorubicin, cisplatin (ddMVAC) and gemcitabine, cisplatin (GC) as neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC).Patient treated at Dana-Farber Cancer Institute from 2010 to 2019 were identified. HRU data on chemotherapy administered, supportive medications, patient monitoring, clinic, infusion, emergency department (ED) visits and hospitalization were collected retrospectively. Unit costs for HRU components were obtained from the Centers for Medicare and Medicaid Website and HRU was compared between groups using quantile regression analysis.137 patients were included; 51 received ddMVAC and 86 GC. Baseline characteristics were similar, except lower mean age (P0.001) and higher proportion of ECOG-PS = 0 (P0.001) for ddMVAC. ddMVAC required more granulocyte-colony stimulating factor support (P0.001), central line placement (P = 0.017), cardiac imaging (P0.001), and infusion visits (P0.001), whereas GC required more clinic visits. ED visits were higher for ddMVAC (P = 0.048), while chemotherapy cycle delays and hospitalization days were higher for GC (P = 0.008). After adjusting for ECOG-PS and age, the cost per patient was approximately 41% lower (95%CI: 28% to 52%; P0.001) for GC vs. ddMVAC, which translated to a median adjusted cost savings of $7,410 (95%CI: $5,474-$9,347) per patient.Although excess HRU did not clearly favor one regimen, adjusting for PS and age indicated lower costs with GC vs. ddMVAC. Given the similar cumulative cisplatin delivery with both regimens, the associated values and costs supports the preferential selection of GC in the neoadjuvant setting of MIBC.

Introduction Nous avons precedemment defini une nouvelle mesure de resultat, la SST (ou TFS en anglais pour Treatment Free Survival) qui designe le delai ecoule entre l’arret des CPI et l’instauration d’un traitement ulterieur ou le deces. La SST fait partie d’une analyse integree permettant de decrire de facon complete comment les pts passent le temps de survie globale (SG), sous et sans traitement, avec/sans toxicite liee au traitement. Nous avons rapporte des donnees de survie, y compris la SST, chez les pts traites par CPI atteints d’un MEL dans l’essai de phase 3 CheckMate 067 ( NCT01844505 ) durant la periode de 36 mois apres la randomisation (Regan. J Clin Oncol.2019) ; Les resultats a 60 mois sont presentes ici. Materiel et methodes Les donnees ont ete analysees chez 937 pts atteint d’un MEL qui ont debute un traitement avec nivolumab (NIVO) plus ipilimumab (IPI), NIVO, ou IPI dans la CheckMate 067. La SST a ete definie comme la zone situee entre les courbes de Kaplan–Meier (KM) pour 2 criteres d’evaluation conventionnels definis a partir de la randomisation : le delai jusqu’a l’arret du traitement de l’etude et le delai jusqu’au traitement ulterieur ou le deces. La SST a egalement ete divisee en SST avec ou sans evenements indesirables lies au traitement (EILT) de grade ≥ 3 et la SG a ete estimee. L’aire sous chaque courbe de KM a ete estimee par le delai moyen restreint a 60 mois jusqu’a l’evenement restreint a 60 mois et exprimee comme un pourcentage de la periode de 60 mois. Des intervalles de confiance a 95 % ont ete calcules pour les differences. Resultats Sur la periode de 60 mois, les pts ont passe en moyenne 33 %, 17 % et 20 % du temps sans traitement apres avoir recu NIVO + IPI, NIVO, et IPI, respectivement (SST moyenne restreinte a 60 mois : 19,7, 9,9 et 11,9 mo). La SST moyenne restreinte a 60 mois des pts traites par NIVO + IPI etait superieure a celle des pts traites par NIVO de 9,8 mois (IC a 95 %, 6,7–12,8) et superieure a celle des pts traites par IPI de 7,8 mois (IC a 95 %, 4,6–11,0). La SST moyenne avec des EILT de grade ≥ 3 correspondait a une faible proportion de la periode de 60 mois : 3 %, 2 % et Discussion Avec un suivi prolonge, la SST moyenne avec ou sans toxicite correspondait a des proportions plus elevees de la periode de 60 mois vs 3 mois pour NIVO + IPI, et NIVO, mais pas pour IPI. Les pts traites avec NIVO + IPI ont continue a avoir une SST deux fois plus longue que celle des patients traites par NIVO seul, en raison de l’arret precoce du traitement pour toxicite sans progression de la maladie et avec une resolution ulterieure d’un grand nombre de ces toxicites. La majeure partie du temps de SST a ete passee sans EILT de grade ≥ 3 dans tous les bras.

Background Conventional measures such as median progression-free survival may suboptimally characterize the full impact of immuno-oncology (I-O) agents vs other systemic anticancer therapies. Patients discontinuing I-O agents may experience periods of disease control without needing subsequent systemic anticancer therapy (Rx) but may still experience toxicity (TOX). Treatment-free survival (TFS) ± TOX can simultaneously characterize disease control and TOX for this off-treatment period. Methods Data were analyzed from all 1082 patients initiating Rx on the randomized phase 3 CheckMate 214 trial of nivolumab + ipilimumab (NIVO+IPI) vs sunitinib (SUN) for treatment-naive predominantly clear cell advanced renal cell carcinoma. TFS is defined as the area between Kaplan–Meier (KM) curves for 2 conventional time-to-event endpoints defined from randomization: time to protocol Rx cessation and time to subsequent Rx or death. TFS was subdivided as TFS with and without TOX by defining a third endpoint: time to cessation of Rx and TOX. TOX was defined as grade ≥3 Rx-related adverse events. Area under each KM curve was estimated by the 36-month restricted mean time to event. Results At 36 months, 60% of NIVO+IPI and 51% of SUN patients were alive, 15% NIVO+IPI and 9% SUN remained on original Rx, and 34% NIVO+IPI and 19% SUN patients were surviving free of subsequent Rx. The 36-month restricted mean TFS was 6.7 and 2.9 months for all NIVO+IPI and SUN patients, respectively (6.4 vs 2.8 months TFS without TOX). The table shows time by TFS subdivision and IMDC risk. Table . 971P IMDC risk group All Favorable Intermediate/Poor N = 547 N = 535 N = 124 N = 119 N = 423 N = 416 Restricted mean time NIVO+IPI SUN Difference NIVO+IPI SUN Difference NIVO+IPI SUN Difference OS, months 28.0 25.6 32.0 32.9 26.9 23.5 Time on protocol Rx, months 13.4 12.7 13.5 20.1 13.4 10.6 TFS, months (95% CI) 6.7 2.9 3.8 (2.4–5.3) 9.8 2.7 7.2 (4.4–10.0) 5.8 3.0 2.8 (1.7–4.0) TFS with TOX 0.4 0.1 0.2 (0.05–0.4) 0.5 0.1 0.4 (0.2–0.6) 0.3 0.2 –0.1 (–0.03–0.3) TFS without TOX 6.4 2.8 3.6 (2.3–5.0) 9.4 2.6 6.8 (4.1–9.5) 5.5 2.8 2.7 (1.6–3.8) Survival after subsequent Rx initiation, months 7.9 10.0 8.7 10.2 7.7 10.0 IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; OS, overall survival. Conclusions NIVO+IPI provides longer survival and delayed time to subsequent Rx vs SUN. More importantly, NIVO+IPI provides longer TFS without TOX, during which patients do not require Rx and are free from TOX. Given the durability of I-O responses relative to SUN after Rx cessation, it will be of interest to measure TFS over time. Clinical trial identification NCT02231749. Editorial acknowledgement Nicolette Belletier, PhD, and Lawrence Hargett of Parexel. Legal entity responsible for the study Bristol-Myers Squibb. Funding Bristol-Myers Squibb and ONO Pharmaceutical Company Limited. Disclosure M.M. Regan: Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): IPSEN; Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Veridex; Research grant / Funding (institution): OncoGenex; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Ferring; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pierre Fabre; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Millennium Pharmaceuticals; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Sotio; Research grant / Funding (institution): Dendreon; Research grant / Funding (institution): Medivation. M.B. Atkins: Honoraria (self), Advisory / Consultancy: BMS; Advisory / Consultancy: Genentech; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: X4 Pharma; Advisory / Consultancy: Merck; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Acceleron; Advisory / Consultancy: Eisai; Advisory / Consultancy: Glactone Pharma; Advisory / Consultancy: Agenus; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Aduro Biotech; Advisory / Consultancy: Newlink Genetics/Pharmatech; Advisory / Consultancy: Arrowhead Pharmaceuticals; Advisory / Consultancy: Werewolf Pharma; Advisory / Consultancy: Oncolys BioPharma; Advisory / Consultancy: Surface; Advisory / Consultancy: Iovance Biotherapeutics. T. Powles: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self): Merck; Honoraria (self): BMS; Honoraria (self): Pfizer; Honoraria (self): IPSEN; Honoraria (self): Novartis; Honoraria (self): Exelixis. S. Yang: Shareholder / Stockholder / Stock options, Full / Part-time employment: BMS. J.L. Johansen: Shareholder / Stockholder / Stock options, Full / Part-time employment: BMS. S. Rao: Shareholder / Stockholder / Stock options, Full / Part-time employment: BMS. K.M. Gooden: Shareholder / Stockholder / Stock options, Full / Part-time employment: BMS. D.F. McDermott: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: X4 Pharma; Advisory / Consultancy: Array Biophrama; Advisory / Consultancy, Research grant / Funding (institution): Peloton Therapeutics; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: Jounce Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Alkermes; Advisory / Consultancy: Lilly; Full / Part-time employment: BIDMC; Research grant / Funding (institution): Promethus Laboratories. All other authors have declared no conflicts of interest.