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Introduction Prior to implementing a new computerized prescription order entry (CPOE) application, the potential risks associated with this system were assessed and compared to those of paper-based prescriptions. The goal of this study is to identify the vulnerabilities of the CPOE process in order to adapt its design and prevent these potential risks. Methods and materials Failure mode and effects analysis (FMEA) was used as a prospective risk-management technique to evaluate the chemotherapy medication process in a university hospital oncology clinic. A multidisciplinary team assessed the process and compared the critical steps of a newly developed CPOE application versus paper-based prescriptions. The potential severity, occurrence and detectability were assessed prior to the implementation of the CPOE application in the clinical setting. Results The FMEA led to the identification of 24 process steps that could theoretically be vulnerable, therefore called failure modes. These failure modes were grouped into four categories of potential risk factors: prescription writing, patient scheduling, treatment dispensing and patient follow-up. Criticality scores were calculated and compared for both strategies. Three failure modes were prioritized and led to modification of the CPOE design. Overall, the CPOE pathway showed a potential risk reduction of 51% compared to paper-based prescriptions. Conclusion FMEA was found to be a useful approach to identify potential risks in the chemotherapy medication process using either CPOE or paper-based prescriptions. The e-prescription mode was estimated to result in less risk than the traditional paper mode.

Background Anti-PD-1 has activity in brain metastases (BM). This phase II open labeled non-randomized single arm trial examined the safety and efficacy of combining nivolumab with radiosurgery (SRS) in the treatment of patients with BM from non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). Methods This was a multicenter trial (NCT02978404) in which patients diagnosed with NSCLC or RCC, having ≤ 10 cc of un-irradiated BM and no prior immunotherapy were eligible. Nivolumab (240 mg or 480 mg IV) was administered for up to 2 years until progression. SRS (15–21 Gy) to all un-irradiated BM was delivered within 14 days after the first dose of nivolumab. The primary endpoint was intracranial progression free survival (iPFS). Results Twenty-six patients (22 NSCLC and 4 RCC) were enrolled between August 2017 and January 2020. A median of 3 (1–9) BM were treated with SRS. Median follow-up was 16.0 months (0.43–25.9 months). Two patients developed nivolumab and SRS related grade 3 fatigue. One-year iPFS and OS were 45.2% (95% CI 29.3–69.6%) and 61.3% (95% CI 45.1–83.3%), respectively. Overall response (partial or complete) of SRS treated BM was attained in 14 out of the 20 patients with ≥1 evaluable follow-up MRI. Mean FACT-Br total scores were 90.2 at baseline and improved to 146.2 within 2–4 months (P = .0007). Conclusions The adverse event profile and FACT-Br assessments suggested that SRS during nivolumab was well tolerated. Upfront SRS with the initiation of anti-PD-1 prolonged the 1-year iPFS and achieved high intracranial control. This combined approach merits validation randomized studies.

In the phase 3 OPTIMISMM trial, pomalidomide, bortezomib, and dexamethasone (PVd) demonstrated superior efficacy vs bortezomib and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma previously treated with lenalidomide, including those refractory to lenalidomide. This analysis evaluated outcomes in patients at first relapse (N = 226) by lenalidomide-refractory status, prior bortezomib exposure, and prior stem cell transplant (SCT). Second-line PVd significantly improved PFS vs Vd in lenalidomide-refractory (17.8 vs 9.5 months; P = 0.0276) and lenalidomide-nonrefractory patients (22.0 vs 12.0 months; P = 0.0491), patients with prior bortezomib (17.8 vs 12.0 months; P = 0.0068), and patients with (22.0 vs 13.8 months; P = 0.0241) or without (16.5 vs 9.5 months; P = 0.0454) prior SCT. In patients without prior bortezomib, median PFS was 20.7 vs 9.5 months (P = 0.1055). Significant improvement in overall response rate was also observed with PVd vs Vd in lenalidomide-refractory (85.9% vs 50.8%; P P

Background—smoldering multiple myeloma (SMM) risk of progression to multiple myeloma (MM) is highly heterogeneous and several models have been suggested to predict this risk. Lakshman et al. recently proposed a model based on three biomarkers: bone marrow plasma cell (BMPC) percentage &gt, 20%, free light chain ratio (FLCr) &gt, 20 and serum M protein &gt, 20 g/L. The goal of our study was to test this “20/20/20” model in our population and to determine if similar results could be obtained in another cohort of SMM patients. Method—we conducted a retrospective, single center study with 89 patients diagnosed with SMM between January 2008 and December 2019. Results—all three tested biomarkers were associated with an increased risk of progression: BMPC percentage ≥ 20% (hazard ratio [HR]: 4.28 [95%C.I., 1.90–9.61], p &lt, 0.001), serum M protein ≥ 20 g/L (HR: 4.20 [95%C.I., 1.90–15.53], p = 0.032) and FLCr ≥ 20 (HR: 3.25 [95%C.I., 1.09–9.71], p = 0.035). The estimated median time to progression (TTP) was not reached for the low and intermediate risk groups and was 29.1 months (95%C.I., 3.9–54.4) in the high-risk group (p = 0.006). Conclusions—the 20/20/20 risk stratification model adequately predicted progression in our population and is easy to use in various clinical settings.

Background: Chemotherapy treatments with robust efficacy that preserve quality of life are needed. Tesetaxel is a novel, oral taxane that has potential advantages over currently available taxanes, including: oral administration with a low pill burden and once every 3 week (Q3W) dosing; no observed hypersensitivity reactions; preclinical evidence of central nervous system (CNS) penetration; and improved activity against chemotherapy-resistant tumors. More than 600 patients have been treated with tesetaxel in clinical studies. Tesetaxel had robust monotherapy activity in a Phase 2 study in 38 patients with HER2-, HR+ MBC, with a confirmed objective response rate (ORR) per RECIST 1.1 of 45%. CONTESSA TRIO investigates tesetaxel plus 3 different PD-(L)1 inhibitors in patients with TNBC and tesetaxel monotherapy in elderly patients with HER2- MBC. Trial design: CONTESSA TRIO is a 2-cohort, multinational, multicenter, Phase 2 study. In Cohort 1, 90 patients (with potential expansion to up to 150 patients) with metastatic TNBC who have not received prior chemotherapy for advanced disease will be randomized 1:1:1 to receive tesetaxel at 27 mg/m2 Q3W plus either: (1) nivolumab at 360 mg Q3W; (2) pembrolizumab at 200 mg Q3W; or (3) atezolizumab at 1,200 mg Q3W. Nivolumab and pembrolizumab (PD-1 inhibitors) and atezolizumab (a PD-L1 inhibitor) are approved for the treatment of multiple types of cancer; atezolizumab, in combination with nab-paclitaxel, was recently approved in the U.S. for the treatment of metastatic TNBC. The dual primary endpoints for Cohort 1 are ORR and progression-free survival (PFS). A sample size of 30 patients in each PD-(L)1 inhibitor treatment group has approximately 70% power to detect an ORR difference of 35% or greater between the treatment group with the highest ORR and the treatment group with the lowest ORR. An increase in the sample size to 50 patients in each treatment group will increase the power to approximately 85%. Secondary endpoints include duration of response (DoR) and overall survival (OS). Efficacy results for each of the 3 PD-(L)1 inhibitor combinations will be assessed for correlation with the results of each of the 3 approved PD-L1 diagnostic assays. CONTESSA TRIO is the first randomized clinical study to compare 3 approved PD-(L)1 inhibitors. In Cohort 2, 40 elderly patients (with potential expansion to up to 60 patients) with HER2- MBC who have not received prior chemotherapy for advanced disease will receive tesetaxel monotherapy at 27 mg/m2 Q3W. The primary endpoint for Cohort 2 is ORR. A sample size of 40 will allow the ORR to be estimated with a maximum standard error of < 8%. An increase in the sample size to 60 patients will decrease the maximum standard error to < 6.5%. Secondary endpoints include PFS, DoR and OS. Patients with CNS metastases are eligible for both cohorts. The Study was initiated in March 2019. For further information on this trial, email joconnell@odonate.com or visit clinicaltrials.gov (NCT03952325). Citation Format: Sara Tolaney, Joanne Blum, Igor Bondarenko, Arlene Chan, Noshir DaCosta, Yin-Hsun Feng, Yann Izarzugaza, Sung-Bae Kim, Mei-Ching Liu, Maria Eva Peréz Lopéz, Mafalda Oliveira, Samuel Guan Wei Ow, Michel Pavic, Hope Rugo, Lee Schwartzberg, Agostina Stradella, Stew Kroll, Joseph O'Connell, Thomas Wei, Elizabeth Mittendorf. CONTESSA TRIO: A multinational, multicenter, phase 2 study of tesetaxel plus 3 different PD-(L)1 inhibitors in patients with metastatic triple-negative breast cancer (TNBC) and tesetaxel monotherapy in elderly patients with HER2- metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-08-08.

INTRODUCTION AND OBJECTIVE:Masitinib (MAS) is an oral, small molecule drug that targets mast cell and macrophage activity. These innate immune cells are critical components of the tumor microenviro...

Patients with relapsed/refractory multiple myeloma (RRMM) experience several relapses, and become refractory to successive therapies. In the ICARIA-MM trial (NCT02990338), isatuximab plus pomalidomide-dexamethasone prolonged median progression-free survival (PFS) in patients with RRMM. This subgroup analysis of ICARIA-MM assessed the treatment benefit of isatuximab by prior lines of therapy and refractory status. A total of 307 patients were randomized to isatuximab-pomalidomide-dexamethasone (n = 154) or pomalidomide-dexamethasone (n = 153). Isatuximab (10 mg/kg intravenously) was given weekly in the first 28-day cycle, then every other week. Standard pomalidomide-dexamethasone doses were given. PFS was assessed by prior lines and refractory status. Overall, 102 (66 %) patients receiving isatuximab-pomalidomide-dexamethasone and 101 (66 %) patients receiving pomalidomide-dexamethasone had received 2–3 prior lines; 52 (34 %) and 52 (34 %) had received >3 prior lines, respectively. Median PFS was higher with isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone for patients who received 2–3 prior lines of therapy (12.3 vs. 7.8 months) and >3 prior lines of therapy (9.4 vs. 4.3 months). Median PFS was higher with isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone for patients who were lenalidomide-refractory (11.4 vs. 5.6 months), lenalidomide-refractory at last line (11.6 vs. 5.7 months), refractory to a proteasome inhibitor (PI) (11.4 vs. 5.6 months), and double-refractory (11.2 vs. 4.8 months). Overall response rate (ORR) in patients receiving isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone was 59.0 % versus 31.4 % in lenalidomide-refractory; 60.2 % versus 32.2 % in PI-refractory; and 58.6 % versus 29.9 % in double-refractory patients. Isatuximab-pomalidomide-dexamethasone improved PFS and ORR regardless of prior lines of therapy or refractory status, consistent with the benefit in the overall population. © 2021 The Authors, Amgen Bristol-Myers Squibb, BMS Pfizer Roche Sanofi Celgene Takeda Pharmaceutical Company, TPC Janssen Pharmaceuticals, SB reports honoraria from Amgen, Bristol-Myers Squibb, Celgene, and Janssen; and reports a consultancy/advisory role for Celgene, Janssen, Karyopharm, and Takeda. VV reports a consultancy/advisory role for Astellas, Biocad, Bristol-Myers Squibb, Janssen, Roche, Sanofi, and Takeda. VM reports a consultancy/advisory role for Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda. LK reports honoraria from Amgen, Celgene, Janssen, and Takeda; a consultancy/advisory role for Amgen, Celgene, Janssen, and Takeda; and travel support from Amgen and Janssen. MP reports honoraria from Celgene, Pfizer, and Takeda; consultancy/advisory role for Amgen, Celgene, Janssen, Roche, and Takeda; and research funding from Amgen, Celgene, Janssen, Pfizer, Roche, and Takeda. PGR reports a consultancy/advisory role for Amgen, Janssen, Karyopharm, Oncopeptides, Sanofi, and Takeda; and research funding from Bristol-Myers Squibb, Celgene, Oncopeptides, and Takeda. LP, FV, KW, LB, and YK have no disclosures. FC, SLG, FM, and HvdV are employees of Sanofi., The ICARIA-MM study was sponsored by Sanofi . The authors thank the participating patients and their families, and the study centers and investigators for their contributions to the study. Medical writing support was provided by Stephanie Brillhart, Julian Ball, and Smitha Reddy of Elevate Medical Affairs E (Fairfield, CT, USA), and funded by Sanofi (Cambridge, MA, USA).

Background: Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma.Methods: DANUBE is an open-label, randomised, controlled, phase 3 trial in patients with untreated, unresectable, locally advanced or metastatic urothelial carcinoma, conducted at 224 academic research centres, hospitals, and oncology clinics in 23 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned patients (1:1:1) to receive durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks; or standard-of-care chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility) administered intravenously for up to six cycles. Randomisation was done through an interactive voice–web response system, with stratification by cisplatin eligibility, PD-L1 status, and presence or absence of liver metastases, lung metastases, or both. The coprimary endpoints were overall survival compared between the durvalumab monotherapy versus chemotherapy groups in the population of patients with high PD-L1 expression (the high PD-L1 population) and between the durvalumab plus tremelimumab versus chemotherapy groups in the intention-to-treat population (all randomly assigned patients). The study has completed enrolment and the final analysis of overall survival is reported. The trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24.Findings: Between Nov 24, 2015, and March 21, 2017, we randomly assigned 1032 patients to receive durvalumab (n=346), durvalumab plus tremelimumab (n=342), or chemotherapy (n=344). At data cutoff (Jan 27, 2020), median follow-up for survival was 41·2 months (IQR 37·9–43·2) for all patients. In the high PD-L1 population, median overall survival was 14·4 months (95% CI 10·4–17·3) in the durvalumab monotherapy group (n=209) versus 12·1 months (10·4–15·0) in the chemotherapy group (n=207; hazard ratio 0·89, 95% CI 0·71–1·11; p=0·30). In the intention-to-treat population, median overall survival was 15·1 months (13·1–18·0) in the durvalumab plus tremelimumab group versus 12·1 months (10·9–14·0) in the chemotherapy group (0·85, 95% CI 0·72–1·02; p=0·075). In the safety population, grade 3 or 4 treatment-related adverse events occurred in 47 (14%) of 345 patients in the durvalumab group, 93 (27%) of 340 patients in the durvalumab plus tremelimumab group, and in 188 (60%) of 313 patients in the chemotherapy group. The most common grade 3 or 4 treatment-related adverse event was increased lipase in the durvalumab group (seven [2%] of 345 patients) and in the durvalumab plus tremelimumab group (16 [5%] of 340 patients), and neutropenia in the chemotherapy group (66 [21%] of 313 patients). Serious treatment-related adverse events occurred in 30 (9%) of 345 patients in the durvalumab group, 78 (23%) of 340 patients in the durvalumab plus tremelimumab group, and 50 (16%) of 313 patients in the chemotherapy group. Deaths due to study drug toxicity were reported in two (1%) patients in the durvalumab group (acute hepatic failure and hepatitis), two (1%) patients in the durvalumab plus tremelimumab group (septic shock and pneumonitis), and one (Interpretation: This study did not meet either of its coprimary endpoints. Further research to identify the patients with previously untreated metastatic urothelial carcinoma who benefit from treatment with immune checkpoint inhibitors, either alone or in combination regimens, is warranted.Funding: AstraZeneca.

316 Background: Cabozantinib (cabo) is an oral multi-targeted tyrosine kinase inhibitor (TKI) with activity in mRCC. TKI toxicity, an indicator of adequate drug exposure, has been associated with clinical effectiveness for sunitinib, pazopanib, and axitinib. We explored whether cabo dose reductions (a surrogate for toxicity) were associated with improved clinical outcomes in mRCC. Methods: Using the CKCis database, we performed an analysis of patients treated with cabo in the second-line or later between 2011-2021. We divided the cohort into those needing a dose reduction (DR, defined as less than the starting dose at time of treatment discontinuation) and those who did not (no-DR). We compared outcomes by dose reduction status, including objective response rate (ORR), time to treatment failure (TTF), and overall survival (OS). Results: We identified 260 patients who received cabo, of which 103 (41.0%) needed a DR. Across all lines, the ORR was similar between the DR and non-DR groups: 19.6% vs. 18.9% (p = 0.903) respectively. The median TTF was 12.75 months (95% CI 10.38 – 17.64) in the DR group vs. 6.44 months (95% CI 5.49 – 8.67) in the no-DR group. After adjusting for IMDC risk, the hazard ratio (HR) for TTF comparing DR vs. no-DR was 0.69 (95% CI 0.50 - 0.97, p-value = 0.03). The median OS was 29.6 months (95% CI 19.58 – 42.64) in the DR group vs. 15.28 (95% CI 11.04 – 22.64) in the no-DR group. After adjusting for IMDC risk, the HR for OS comparing DR vs. no-DR was 0.65 (95% CI 0.43 - 0.98, p = 0.04). Conclusions: Cabozantinib dose reductions, a surrogate for toxicity and adequate drug exposure, appear to be associated with improved TTF and OS in mRCC. Toxicity driven/individualized dosing strategies for cabo alone and in combination with immunotherapy, warrant further investigation.[Table: see text]

Background: Erythrocytosis is a frequent request for consultation in the hematologic field. The diagnostic approach is well established in the general population but in a young adult, finding the etiology of erythrocytosis can be a real diagnostic challenge. Methods: This is an observational retrospective unicentric study made at the Sherbrooke University Hospital Center, over a period of 20 years (1995 - 2015). Every patient aged between 16 and 35 years old with a significant elevation of hemoglobin or hematocrit was included (hemoglobin > 185 g/L and/or hematocrit > 0.52 in men; hemoglobin > 165 g/L and/or hematocrit > 0.48 in women). Results: Totally, 426 patients met the inclusion criteria (over a total of 113,453 complete blood counts) but only 56 entered the study for investigations. The majority of patients were of male gender, 43% of the patients were obese, 59% were smokers and 38% used excess alcohol or recreational drugs. Twenty-five patients had the diagnosis of absolute erythrocytosis. Seven patients had the diagnosis of relative erythrocytosis and no cause could be identified in 24 patients. No primary erythrocytosis was found in this cohort. Among the 25 patients with secondary erythrocytosis, hypoxia was the most frequent etiology identified. Less than half of the patients in the cohort had long term follow-up. Search for JAK2 mutation and serum EPO dosage were performed in 17.9% and 23.2% of cases respectively. Seven patients were treated with aspirin and five patients had phlebotomies. Conclusions: This retrospective study reveals an actual clinical management that is often discordant with the current recommendations and a frequent lack of follow-up after initial investigations. Harmonization of management of erythrocytosis appears to be highly desirable. J Hematol. 2018;7(2):43-50 doi: https://doi.org/10.14740/jh375w

Background: Despite recent improvements, myeloma is still incurable. There is need to add new therapeutic tools. The combination of the proteasome inhibitor (PI) Bortezomib, an alkylator (Cyclophosphamide or Melphalan) and Dexamethasone (Dex) /Prednisone is a widely used first-line therapy. Most patients achieve a rapid response within the first two cycles. The lack of a deep response to the bortezomib-based therapy predicts an inferior outcome, a poor response to newer PIs and limited therapeutic options. Different studies highlighted the role of the PD1/PDL1 pathway in myeloma immune escape and progression. The expression of PDL1 by myeloma cells is higher in relapsed or refractory disease and on minimal residual disease cells. At least one preclinical study showed that the binding of PD1 to PDL1 expressed by the myeloma cells leads to a reverse signal that induces resistance to bortezomib and melphalan. Also, Bortezomib is known to enhance anti-myeloma immune response by different mechanisms, including stimulating myeloma cell apoptosis, sensitizing myeloma cells to natural killer cell mediated killing and enhancing antigen presentation by dendritic cells. This suggests a mutual potentiation between Pembrolizumab and Cyclophosphamide, Bortezomib and Dex (CyBorD). An early immune-based intervention is likely more beneficial. With time and disease progression, the host is more immune-compromised and the disease is more refractory with redundant escape mechanisms. The benefits of early intervention are carefully weighed against the potential risks and other available therapeutic options. The adaptive design of this CMRG-006 trial is meant to select the population with the highest need for treatment improvement while still in the early phase of therapy. We expect the combination of Pembrolizumab and CyBorD to be more effective and well tolerated. Design and Methods: Phase 2A, pilot study. Non-transplant eligible newly diagnosed myeloma patients (NTE-NDMM) will start their standard nine cycles of CyBorD (Cyclophosphamide 300 mg/m 2 PO, Bortezomib 1.5 mg/m 2 SC, and Dex 40 mg PO, all given on days 1, 8, 15 and 22 of 28-day cycle). Patients not having primary disease progression and achieving less than Very Good Partial Response (VGPR) after 2 cycles will be screened for this study during cycle 3. Eligible patients will receive Pembrolizumab 200 mg IV every 3 weeks starting with day 1 of cycle 4 (P-CyBorD). After completion of cycle nine of CyBorD, Pembrolizumab will be administered as a single agent for up to total of 35 doses. The objectives are to evaluate the efficacy and tolerability of P-CyBorD. The key inclusion criteria are having a NTE-NDMM with a measurable disease; no primary progressive disease and not achieving VGPR after two cycles of CyBorD; adequate performance status; and adequate organ functions. The key exclusion criteria include previous exposure to anti-PD1 therapy, intolerance to CyBorD, adverse cardiac history, pulmonary disease, central nervous system disease, congenital or acquired immune suppression, and AL amyloidosis. S ample Size: A maximum of 20 patients will be enrolled to ensure 16 or more patients evaluable for response. Patients with less than VGPR after two cycles of CyBorD have ≤20% probability to achieve ≥VGPR after cycle 9. With the addition of Pembrolizumab, a minimal clinically important difference (MCID) of 10% would be meaningful, and a 50% response rate (≥VGPR) in 16 evaluable patients will be statistically significant. This study is currently recruiting. Clinicaltrials.gov #: NCT04258683. Disclosures Kotb: Amgen: Honoraria; BMS: Honoraria; Merck: Honoraria, Research Funding; Karyopharm: Current holder of individual stocks in a privately-held company; Takeda: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Sanofi: Honoraria, Research Funding; Akcea: Honoraria; Pfizer: Honoraria. Othman: Takeda: Honoraria; Roche: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Celgene: Honoraria. Reece: Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Honoraria; Millennium: Research Funding; BMS: Honoraria, Research Funding; Karyopharm: Consultancy, Research Funding; Amgen: Consultancy, Honoraria; GSK: Honoraria.

Purpose/objective(s) Previous studies have suggested activity of anti-PD1 antibodies against brain metastases from non-small cell lung cancer (NSCLC) and renal cell cancer (RCC). Our investigator-initiated phase 2 trial examined the neuropsychological effect of combining nivolumab with radiosurgery (SRS) in the treatment of patients with brain metastases from NSCLC and RCC. Materials/methods This is a multicenter open-label trial (NCT02978404) in which patients diagnosed with NSCLC or RCC, having ≤ 10 cc of un-irradiated brain metastases, no prior whole brain radiotherapy and no prior immunotherapy were eligible. Study treatment commenced with a dose of nivolumab (240mg or 480mg IV), which was continued until progression for up to 2 years at bi-weekly or monthly intervals. SRS (15-21 Gy) to all visible un-irradiated brain lesions was administered within 14 days of the first dose of nivolumab (cycle 1). Patients were followed by brain MRI and CT scans of the chest, abdomen and pelvis. Neurocognitive assessment was performed using the Hopkins verbal learning test-revised (HVLT-R), the Trail Making Test (TMT) and the Controlled Oral Word Association Test (COWA) RESULTS: 26 study patients (22 NSCLC and 4 RCC) were enrolled between Aug 2017 and January 2020. Patients had a median of 2 (1-9) brain metastases treated with SRS. The median diagnosis-specific graded prognostic assessment (GPA) score was 2 (1-3). Forty-two percent of the patients had received prior cytotoxic chemotherapy, and 1 patient had received prior brain SRS. PD-L1 status was known for 21 of the 22 NSCLC patients (12 with ≥50% PD-L1 expression (DAKO 22C3)). Median icPFS was 5.0 months (6 intracranial progressions and 9 deaths without progression in the brain). Accounting for death as a competing risk, the 1-year cumulative incidence of intracranial relapse was 20%, whereas the rate of extracranial relapse was 48.3% at 1-year. Median overall survival was 14 months. Neuropsychological evaluation was completed in 16 and 9 patients at 3 and 6-month follow-up, respectively. Median age of the 16 patients was 63 (46-77). At 3 months follow up, there was no significant difference on the patient's mean performance in any of the neurocognitive assessments; a deterioration of ≥1 standard deviation in at least 1 assessment from baseline was observed in 8 (50%) patients. At 6 months, participants significantly improved on the TMT- Parts A (P = 0.04) and Parts B (P = 0.03). Conclusion Neurocognitive assessments suggest that upfront SRS concurrent with nivolumab PD1 inhibition is safe. Patient neurocognitive function showed potential improvements in patients able to complete 6-month assessments. A potential synergy between nivolumab and SRS loco-regionally within the brain may be present, leading to high intracranial control. However, the high rate of extracranial progression does not suggest an abscopal effect triggered by SRS during nivolumab. Author disclosure G.L. Masucci: Research Grant; BMS.O. Boucher: None. F. Marie: None. M. Plourde: None. V. Panet-Raymond: None. M. Pavic: None. S. Owen: None. L. Masson-Cote: None. C. Menard: Research Grant; Siemens Healthcare, Philips, Progenics, Varian. B. Routy: None. M. Tehfe: None. N. Blais: consultant; BMS.D. Roberge: Independent Contractor; CHUM, CDL Proton Therapy. Research Grant; Elekta. Honoraria; BrainLab, Varian Medical Systems, Siemens Medical Systems, EMD Serono, recordati. In-kind Donation; Accuray. ownership stake; afx, croton healthcare. P. Wong: Research Grant; BMS, AstraZeneca, NexPlasmaGen. Advisory Board; BMS, AstraZeneca. Travel Expenses; BMS, AstraZeneca.

Cancer-related fatigue (CRF) is a major issue in older cancer patients as it is associated with functional decline and a lower quality of life, and an increased inflammatory activity during cancer therapy is suspected to play a key role in CRF etiology. Combined aerobic and resistance exercise training is known to reduce CRF, and this could be mediated by a protective effect against this increased inflammatory activity. Hence, the main objective was to measure the effect of a 12-week combined exercise training on the inflammatory profile of older cancer patients undergoing systemic therapy. A secondary objective was to verify if there was an association between inflammatory profile and CRF. Methods Twenty older non-metastatic cancer patients initiating chemotherapy and/or hormone therapy were randomly assigned to 12 weeks of supervised, combined exercise or a control group (static stretching). Primary outcomes were the inflammatory profile, Indoleamine 2,3-deoxygenase activity (KYN/TRP ratio), and CRF (FACIT-F questionnaire). Control outcomes were the fasting nutritional and hormonal blood profiles, body composition (iDXA), physical activity habits (PASE questionnaire), nutritional habits (3-day log), and treatment-related variables. Results No worsening of the inflammatory profile was observed in both arms of the study after the intervention. No significant change in CRF was observed, although there was a trend for a reduction in the experimental group (p ​= ​0.10). Significant correlations were found at both timepoints between the KYN/TRP ratio and the delay with the previous treatment received (p ​≤ ​0.03). Conclusion These results suggest that exercise might have elicited a positive effect on CRF, which was not mediated by the modulation of the pro-inflammatory cytokine profile. However, the decrease in IL-6/IL-10 ratio in the exercise group might reflect a possible anti-inflammatory effect of exercise. Moreover, exploratory analyses suggest that an acute effect of chemotherapy treatments influenced the inflammatory profile measurements, which could explain the absence of change in the fasting inflammatory profile., Highlights • We studied the anti-inflammatory effect of exercise in older cancer patients undergoing chemotherapy. • Exercise could alter the ratio of anti-to pro-inflammatory markers during chemotherapy. • Chemotherapy might induce acute inflammatory peaks in the week following treatment. • We propose that exercise could interact acutely with these pro-inflammatory peaks.

2023 Background: Previous studies suggested activity of anti-PD-1 in brain metastases from non-small cell lung cancer (NSCLC) and renal cell cancer (RCC). This investigator initiated phase 2 trial examined the safety and efficacy of combining nivolumab with radiosurgery (SRS) in the treatment of patients with brain metastases from NSCLC and RCC. Methods: This is a multicentre open-label trial (NCT02978404) in which patients diagnosed with NSCLC or RCC, having ≤ 10 cc of un-irradiated brain metastases, no whole brain radiotherapy and no prior immunotherapy were eligible. Study treatment commenced with a dose of nivolumab (240mg or 480mg IV), which was continued for up to 2 years at bi-weekly or monthly intervals until progression. SRS (15-21Gy) to all visible un-irradiated brain lesions was administered within 14 days after the first dose of nivolumab (cycle 1). Patients were followed by brain MRI, CT scan of the chest, abdomen and pelvis, neurocognitive and quality of life questionnaires (FACT-Br) every 3 months. The primary endpoint was intracranial progression free survival (icPFS), with death and disease progression within the brain as events. Results from NSCLC patients are presented here. Results: Of the 26 study patients, 22 NSCLC patients were enrolled between Aug 2017 and January 2020. Patients had a median of 2 (1-9) brain metastases. The median diagnosis-specific graded prognostic score was 2 (1-3). Median treatment and follow-up durations were 4.3 months (0-24.8 months) and 11 months (0-24.8 months), respectively. Forty-two percent of the patients had received prior cytotoxic chemotherapy, and 1 patient had received prior brain SRS. PD-L1 status was known for 21 of the 22 NSCLC (12 with ≥50% PD-L1 expression (DAKO 22C3). Median icPFS was 5.0 months (3 intracranial progression and 8 deaths without progression in the brain). Accounting for death as a competing risk, the 1-year cumulative incidence of intracranial relapse was 17.4%. Median extracranial PFS and overall survival were 2.9 months and 14 months, respectively. Four grade 3 adverse events in 2 patients were related to nivolumab or SRS. The rate of survival free of neurocognitive decline (Hopkins Verbal Learning Test total recall) was estimated to be 89% by 4 months. Mean FACT-Br total scores were 89.4 at baseline and improved (p = 0.01) to 139.3 within 2-4 months. Conclusions: Neurocognitive and quality of life assessments suggest that upfront SRS during nivolumab is well tolerated. High intracranial control was observed, but deaths from extracranial disease progression resulted in short icPFS. Studies evaluating the strategic addition of SRS combined with more efficacious systemic treatments are needed. Clinical trial information: 02978404.

e20005 Background: Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder associated with a high risk of transformation to symptomatic multiple myeloma (MM). SMM risk of progression to MM is highly heterogeneous and several models have been suggested to predict this risk, but none have yet been adopted internationally. Lakshman et al. recently proposed a risk stratification model based on three markers: bone marrow plasma cell (BMPC) percentage > 20%, free light chain ratio (FLCr) > 20 and serum M protein > 20 g/L. In this “20/20/20” model, patients with 0, 1 or ≥ 2 risk factors are respectively considered at low, intermediate and high-risk of progression. The goal of our study was to test this risk model in our population and to determine if similar results could be obtained in another cohort of SMM patients. Methods: We conducted a retrospective, single center study with 89 patients diagnosed with SMM between January 2008 and December 2019. Patients were identified by query of the electronic medical records and the 2014 International Myeloma Working Group (IMWG) diagnostic criteria for SMM were used to determine eligibility. The main endpoint was progression to symptomatic multiple myeloma or amyloidosis. Results: All three markers proposed by Lakshman et al. were associated with an increased risk of progression: BMPC percentage ≥ 20% (hazard ratio [HR]: 4.28 [95% C.I., 1.90 – 9.61]; p < 0.001), serum M protein ≥ 20g/L (HR: 4.20 [95% C.I., 1.90 – 15.53]; p = 0.032) and FLCr ≥ 20 (HR: 3.25 [95% C.I., 1.09 – 9.71]; p = 0.035). Immunoparesis (HR: 2.61 [95% C.I., 1.07 – 6.41]; p = 0.036) was also an independent risk factor in our population. The estimated median time to progression (TTP) was not reached for the low and intermediate risk groups and was 29.1 months (95% C.I., 3.9 – 54.4) in the high-risk group (p = 0.006). The estimated mean TTP for the low-risk group, the intermediate-risk group and the high-risk group were respectively 78.4 months (95% C.I., 68.3 – 88.5), 48.3 months (95% C.I., 31.9 – 64.8) and 35.2 months (95% C.I., 19.1 – 51.2). Sex, IgA isotype, positive Bence-Jones, abnormal β2-microglobulin and MGUS prior to SMM did not result in an increased risk of progression. The estimated proportion of progression-free patients at 1, 2 and 5 years were 96.8%, 93.4% and 77.5% for the low-risk group, 80.0%, 80.0% and 62.2% for the intermediate risk group and 70.0%, 58.3% and 29.2% for the high-risk group. Conclusions: When Mayo Clinic’s new 20/20/20 risk model was applied to our population, it adequately predicted the risk of progression to symptomatic disease at 2 years. As it relies on readily available biological parameters, this model is easy to use and can be applied in most clinical settings. We believe this model could be used to further study therapeutic approaches in higher risk SMM.

After a diagnosis of cancer, physical activity has prooved positive impact on biopsychosocial aspects and survival. Physical activity promotion is crucial for all patients, at any age, during and after treatments. Moreover, Adapted Physical Activity (APA) must be integrated in patients’ care. Factors limiting physical practice and cancer stages must be considered in patient management. Patients must be accompanied in becoming autonomous in physical activity, in a regular and sustainable manner. It is important to place the patient at the center of the physical activity management and to accompany him to integrate new behaviors in his daily life. Stakeholders – caregivers, APA trainers, physiotherapists, sports trainers trained to oncology – will take care of patients, in a multidisciplinary approach.

TPS1111 Background: Chemotherapy treatments with robust efficacy that preserve quality of life are needed. T is a novel, oral taxane that has potential advantages over currently available taxanes, including: oral administration with a low pill burden and once every 3 week (Q3W) dosing; no observed hypersensitivity reactions; preclinical evidence of central nervous system (CNS) penetration; and improved activity against chemotherapy-resistant tumors. More than 600 pts have been treated with T in clinical studies. T had robust monotherapy activity in a P2 study in 38 pts with HER2-, HR+ MBC, with a confirmed objective response rate (ORR) per RECIST 1.1 of 45%. Methods: CONTESSA TRIO is a 2-cohort, multinational, multicenter, P2 study. In Cohort 1, 90 pts (potential expansion to up to 150 pts) with metastatic TNBC who have not received prior chemotherapy for advanced disease will be randomized 1:1:1 to receive T at 27 mg/m2 Q3W plus either: (1) nivolumab at 360 mg Q3W; (2) pembrolizumab at 200 mg Q3W; or (3) atezolizumab at 1,200 mg Q3W. Nivolumab and pembrolizumab (PD-1 inhibitors) and atezolizumab (a PD-L1 inhibitor) are approved for the treatment of multiple types of cancer; atezolizumab, in combination with nab-paclitaxel, was recently approved in the US for the treatment of metastatic TNBC. The dual primary endpoints for Cohort 1 are ORR and progression-free survival (PFS). A sample size of 30 pts in each PD-(L)1 inhibitor treatment group has approximately 70% power to detect an ORR difference of ≥ 35% between the treatment group with the highest ORR and the treatment group with the lowest ORR. Secondary endpoints include duration of response (DoR) and overall survival (OS). Efficacy results for each of the 3 PD-(L)1 inhibitor combinations will be assessed for correlation with the results of each of the 3 approved PD-L1 diagnostic assays. CONTESSA TRIO is the first randomized clinical study to compare 3 approved PD-(L)1 inhibitors. In Cohort 2, 40 elderly pts (potential expansion to up to 60 pts) with HER2- MBC who have not received prior chemotherapy for advanced disease will receive T monotherapy at 27 mg/m2 Q3W. The primary endpoint for Cohort 2 is ORR. A sample size of 40 will allow the ORR to be estimated with a maximum standard error of < 8%. Secondary endpoints include PFS, DoR and OS. Pts with CNS metastases are eligible for both cohorts. The study was initiated in March 2019. Clinical trial information: NCT03952325 .

Background: Kinesiophobia, the fear that movement and physical activity could worsen side effects such as fatigue and pain, is a barrier to exercise in cancer patients. Physical inactivity and deconditioning can lead to functional decline, higher mortality risk and lower quality of life, in older adults, and even more in oncogeriatrics because of a lower physical activity level during cancer treatments. The case: We present the case of an older breast cancer patient recruited in a controlled exercise trial and randomized to the control arm of the study (a 12-week supervised static stretching program). She expressed fear that physical activity might exacerbate some of her cancer-related symptoms during baseline physical capacity assessment (Senior Fitness Test, handgrip strength and maximal lower body strength). After completing the 12-week supervised static stretching program, she exhibited similar and/or larger improvements in many of the physical capacity tests than the mixed exercise intervention group, despite being in the control arm. Conclusions: These observations and physical capacity results have led us to emit the hypothesis that (1) this participant’s baseline physical capacity assessment might have been biased by kinesiophobia and (2) the supervision by exercise physiologist might have mitigated this fear over time. Hence, based on this case, we suggest that kinesiophobia should be measured in future exercise trials and clinical interventions targeting older cancer patients.

BACKGROUND Lenalidomide (LEN), an established treatment (Tx) for newly diagnosed multiple myeloma, is routinely administered until disease progression. Therefore, patients (pts) for whom LEN is no longer an option at first relapse, including LEN-refractory pts, are a clinically relevant and growing population. Tx of these pts remains challenging, as they have been poorly represented in phase 3 clinical trials. OPTIMISMM (NCT01734928), a phase 3 trial specifically designed to address this population, demonstrated significantly improved progression-free survival (PFS) with pomalidomide (POM), bortezomib (BORT), and low-dose dexamethasone (PVd) compared with BORT and low-dose dexamethasone (Vd) in pts who received 1-3 prior regimens and were 100% LEN pretreated (70% LEN refractory) (Richardson PG, et al. Lancet Oncol. 2019;20:781-794). Here, we report the efficacy and safety of PVd in pts treated after 1 prior line of therapy (LOT) according to age, prior stem cell transplant (SCT), and in pts with high-risk cytogenetic abnormalities (HR CAs). METHODS Pts were randomized 1:1 to receive PVd or Vd in 21-day cycles. POM 4 mg/day was given on days 1-14 (PVd arm only); bortezomib (BORT) 1.3 mg/m2 was given on days 1, 4, 8, and 11 of cycles 1-8 and on days 1 and 8 of cycles 9+; and dexamethasone 20 mg/day (10 mg/day for pts aged > 75 yrs) was given on the days of and after BORT. Key eligibility criteria included ≥ 2 cycles of prior LEN, including LEN-refractory pts. The primary endpoint was PFS. RESULTS As of October 26, 2017, 226 of 559 pts enrolled in OPTIMISMM had 1 prior LOT; 100 pts were aged ≤ 65 yrs (49 PVd, 51 Vd) and 126 were aged > 65 yrs (62 PVd, 64 Vd). In pts aged ≤ 65 yrs (PVd vs Vd), the median age was 58.0 vs 59.0 yrs, 63.3% vs 47.1% were male, 55.1% vs 51.0% were LEN refractory, and 83.7% vs 72.5% had prior BORT. In pts aged > 65 yrs, the median age was 73.0 vs 71.5 yrs, 58.1% vs 51.6% were male, 59.7% vs 60.9% were LEN refractory, and 41.9% vs 46.9% had prior BORT. After 1 prior LOT, PVd vs Vd significantly improved PFS in pts aged ≤ 65 yrs (median, 22.0 vs 13.1 mos; P = .0305) and those > 65 yrs (median, 17.6 vs 9.9 mos; P = .0348) (Figure). The overall response rate (ORR) was significantly higher with PVd vs Vd across the age groups (Table). The rate of ≥ very good partial response (VGPR) was 65.3% vs 17.6% in pts aged ≤ 65 yrs and 58.1% vs 26.6% in pts aged > 65 yrs. Comparable PFS and ORR outcomes were noted for an age cutoff of ≤ 70 yrs (median PFS, 17.8 vs 13.1 mos with PVd [n = 71] vs Vd [n = 78]; ORR, 88.7% [≥ VGPR, 62.0%] vs 55.1% [≥ VGPR, 21.8%], respectively) vs > 70 yrs (median PFS, 16.5 vs 9.5 mos with PVd [n = 40] vs Vd [n = 37]; ORR, 92.5% [≥ VGPR, 60.0%] vs 54.1% [≥ VGPR, 24.3%], respectively). These PFS and ORR findings were similar to those reported in pts with and pts without prior SCT (Table). Median PFS was 22.0 mos with PVd vs 13.8 mos with Vd in pts with prior SCT (P = .0241) and 16.5 vs 9.5 mos, respectively, in pts without prior SCT (P = .0454). Pts with HR CAs (n = 32 [18 PVd, 14 Vd]), defined as having a del(17p), t(4;14), or t(14;16), had a median PFS of 14.7 mos with PVd and 9.9 mos with Vd. The most common grade 3/4 treatment-emergent adverse events (TEAEs) with PVd vs Vd were neutropenia (49.0% vs 6.3%), infections (30.6% vs 14.6%), and thrombocytopenia (26.5% vs 18.8%) in pts aged ≤ 65 yrs and neutropenia (25.8% vs 12.9%), infections (27.4% vs 16.1%), and thrombocytopenia (14.5% vs 22.6%) in pts aged > 65 yrs. CONCLUSIONS In pts with LEN-pretreated relapsed or refractory multiple myeloma at first relapse, PVd reduced the risk of progression or death by 50% in pts aged ≤ 65 yrs and by 43% in pts aged > 65 yrs vs Vd. Additionally, across age subgroups, second-line Tx with PVd vs Vd significantly improved ORR and led to deeper responses. Similar findings were observed in pts with and pts without prior SCT. PVd also benefited pts with HR CAs vs Vd. Overall, TEAEs with PVd were generally consistent with the known profiles of the constituent agents. These data in pts at first relapse continue to demonstrate that PVd is effective and safe as a second-line Tx following LEN, regardless of age, prior SCT status, and presence of HR CAs. Disclosures Dimopoulos: Sanofi Oncology: Research Funding. Weisel:GSK: Honoraria; Juno: Consultancy; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Adaptive Biotech: Consultancy, Honoraria; Celgene Corporation: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Moreau:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Anderson:Amgen, Janssen, Takeda, Celgene: Consultancy, Speakers Bureau. White:Sanofi: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. San-Miguel:Amgen, Bristol-Myers Squibb, Celgene, Janssen, MSD, Novartis, Roche, Sanofi, and Takeda: Consultancy, Honoraria. Sonneveld:SkylineDx: Research Funding; Takeda: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; BMS: Honoraria; Amgen: Honoraria, Research Funding. Jenner:Abbvie, Amgen, Celgene, Novartis, Janssen, Sanofi Genzyme, Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Dürig:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Celgene: Consultancy, Other: Travel or accommodations, Speakers Bureau. Pavic:Celgene, Janssen, Takeda, Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Casal:Celgene Corporation: Employment. Srinivasan:Celgene: Employment, Equity Ownership. Nguyen:Celgene Corporation: Employment, Equity Ownership. Biyukov:Celgene: Employment, Equity Ownership. Peluso:Celgene Corporation: Employment. Richardson:Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Yes. The triplet combination is not currently approved in the US for the treatment of multiple myeloma.

BACKGROUND: Isatuximab is a monoclonal antibody that binds a specific epitope on the human CD38 receptor and has antitumour activity via multiple mechanisms of action. In a previous phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of isatuximab with pomalidomide and low-dose dexamethasone. The aim of this study was to determine the progression-free survival benefit of isatuximab plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma. METHODS: We did a randomised, multicentre, open-label, phase 3 study at 102 hospitals in 24 countries in Europe, North America, and the Asia-Pacific regions. Eligible participants were adult patients with relapsed and refractory multiple myeloma who had received at least two previous lines of treatment, including lenalidomide and a proteasome inhibitor. Patients were excluded if they were refractory to previous treatment with an anti-CD38 monoclonal antibody. We randomly assigned patients (1:1) to either isatuximab 10 mg/kg plus pomalidomide 4 mg plus dexamethasone 40 mg (20 mg for patients aged ≥75 years), or pomalidomide 4 mg plus dexamethasone 40 mg. Randomisation was done using interactive response technology and stratified according to the number of previous lines of treatment (2-3 vs >3) and age (

Aging, cancer and its treatment all contribute to increase the risk of deconditioning and sedentary behaviors. Mixed exercise is recognized to counteract the effects of aging and deconditioning as well as improving physical capacity during cancer treatment in adults. To determine the impact of a mixed exercise program (MXEP) to improve physical capacity and decrease sedentary behavior time (SBT) in older adults during cancer treatment. Fourteen participants (68.8 ± 3.4 years) completed 12 weeks of a mixed exercise program (MEXP) (n = 6) or stretching (n = 8) while they were under cancer treatment. Five tests of the Senior Fitness Test (Chair Stand, 8-Foot Up & Go, Arm Curl, Sit & Reach, 6 min Walk Test), two maximal strength tests (leg press and handgrip) and a Global Physical Capacity Score (GPCS) were used to assess physical capacity. For the amount of SBT (min/day), we used question 1 of the Physical Activity Scale for the Elderly. Both groups presented significant pre- vs post-intervention differences for the Chair Stand, Arm Curl, 6 min Walk Tests and also GPCS. Nevertheless, this difference was significantly greater in the MEXP group only for the Chair Stand Test (4.3 ± 2.2 vs 1.0 ± 1.3 reps; p = 0.01) and the GPCS (4.0 ± 0.6 vs 1.5 ± 2.3 points; p = 0.047). A tend to display a greater decrease in SBT (− 295 ± 241 min/week vs − 11 ± 290 min/week; p = 0.079) was observed in favor of MEXP. A 12-week mixed exercise program led to significant improvements in physical capacity and may reduce SBT.

WOS: 000491229800404, [No abstract available]

Background Chemotherapy (CT) treatments with robust efficacy that preserve quality of life are needed. Tesetaxel (T) is a novel, oral taxane that has potential advantages over currently available taxanes, including: oral administration with a low pill burden and once every 3 week (Q3W) dosing; no observed hypersensitivity reactions; and preclinical evidence of central nervous system (CNS) penetration and improved activity against CT-resistant tumors. More than 600 pts have been treated with T in clinical studies. T had robust monotherapy activity in a phase 2 study in 38 pts with HER2-, HR+ MBC, with a confirmed objective response rate (ORR) per RECIST 1.1 of 45%. Trial design CONTESSA TRIO is a 2-cohort, multinational, multicenter, Phase 2 study. In Cohort 1, 90 pts (with potential expansion to up to 150 pts) with metastatic TNBC who have not received prior CT for advanced disease will be randomized 1:1:1 to receive T at 27 mg/m2 Q3W plus either: (1) nivolumab at 360 mg Q3W; (2) pembrolizumab at 200 mg Q3W; or (3) atezolizumab at 1,200 mg Q3W. Nivolumab and pembrolizumab (PD-1 inhibitors) and atezolizumab (a PD-L1 inhibitor) are approved for the treatment of multiple types of cancer; atezolizumab, in combination with nab-paclitaxel, was recently approved in the U.S. for the treatment of metastatic TNBC. The dual primary endpoints for Cohort 1 are ORR and progression-free survival (PFS). Secondary endpoints include duration of response (DoR) and overall survival (OS). Efficacy results for each of the 3 PD-(L)1 inhibitor combinations will be assessed for correlation with the results of each of the 3 approved PD-L1 diagnostic assays. CONTESSA TRIO is the first randomized clinical study to compare 3 approved PD-(L)1 inhibitors. In Cohort 2, 40 elderly pts (with potential expansion to up to 60 pts) with HER2- MBC who have not received prior CT for advanced disease will receive T monotherapy at 27 mg/m2 Q3W. The primary endpoint for Cohort 2 is ORR. Secondary endpoints include PFS, DoR and OS. Pts with CNS metastases are eligible for both cohorts. The Study was initiated in March 2019. Clinical trial identification EudraCT: 2018-004715-41. Legal entity responsible for the study Odonate Therapeutics, Inc. Funding Odonate Therapeutics, Inc. Disclosure S.M. Tolaney: Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Cyclacel; Advisory / Consultancy, Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Odonate Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Nektar Therapeutics; Advisory / Consultancy: Tesaro; Advisory / Consultancy: NanoString Technologies; Advisory / Consultancy: Puma Biotechnology. J.L. Blum: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Medivation; Advisory / Consultancy: Novartis; Research grant / Funding (institution): Bristol-Myers Squibb. A. Chan: Research grant / Funding (institution): Eisai; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Puma Biotechnology; Speaker Bureau / Expert testimony: Prime Oncology; Travel / Accommodation / Expenses: Pierre Fabre. Y. Feng: Research grant / Funding (institution), Full / Part-time employment: Chi Mei Medical Center. S. Kim: Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Sanofi-Genzyme; Research grant / Funding (institution): DongKook Pharmaceutical. M. Liu: Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca. M. Oliveira: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Philips Healthcare; Research grant / Funding (institution): Genentech; Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Boehringer-Ingelheim; Travel / Accommodation / Expenses: Pierre-Fabre; Travel / Accommodation / Expenses: GP Pharma; Travel / Accommodation / Expenses: Grunenthal. M. Pavic: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Celgene; Honoraria (self): Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Astellas Pharma; Travel / Accommodation / Expenses: Taiho Pharmaceutical; Travel / Accommodation / Expenses: Bayer. H.S. Rugo: Research grant / Funding (institution), Travel / Accommodation / Expenses, Mandatory publication support: Roche/Genentech; Research grant / Funding (institution), Travel / Accommodation / Expenses, Mandatory publication support: Pfizer; Travel / Accommodation / Expenses: Puma Biotechnology; Travel / Accommodation / Expenses: Mylan; Travel / Accommodation / Expenses: Daiichi Sankyo; Research grant / Funding (institution), Travel / Accommodation / Expenses: MacroGenics; Honoraria (self): Celltrion; Research grant / Funding (institution): OBI Pharma; Research grant / Funding (institution): Eisai; Research grant / Funding (institution), Mandatory publication support: Novartis; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Odonate Therapeutics; Research grant / Funding (institution), Travel / Accommodation / Expenses, Mandatory publication support: Roche/Genentech; Research grant / Funding (institution), Travel / Accommodation / Expenses, Mandatory publication support: Pfizer; Travel / Accommodation / Expenses: Puma Biotechnology; Travel / Accommodation / Expenses: Mylan; Travel / Accommodation / Expenses: Daiichi Sankyo; Research grant / Funding (institution), Travel / Accommodation / Expenses: MacroGenics; Honoraria (self): Celltrion; Research grant / Funding (institution): OBI Pharma; Research grant / Funding (institution): Eisai; Research grant / Funding (institution), Mandatory publication support: Novartis; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Odonate Therapeutics. L. Schwartzberg: Advisory / Consultancy, Research grant / Funding (institution): Helsinn; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Merck; Advisory / Consultancy: Heron Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Amgen; Speaker Bureau / Expert testimony: Coherus BioSciences; Speaker Bureau / Expert testimony: Puma Biotechnology. A. Stradella: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Celgene. S. Kroll: Shareholder / Stockholder / Stock options, Full / Part-time employment: Odonate Therapeutics. J. O’Connell: Leadership role, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Odonate Therapeutics; Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: inVentiv Health. T. Wei: Shareholder / Stockholder / Stock options, Full / Part-time employment: Odonate Therapeutics. E.A. Mittendorf: Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy: Genomic Health; Advisory / Consultancy: Merck; Advisory / Consultancy: Peregrine Pharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution): Sellas Lifesciences; Advisory / Consultancy: Tapimmune. All other authors have declared no conflicts of interest.

Aim: To assess the clinical features and outcome of lymphoma when associated with sarcoidosis and to determine whether this association gives lymphoma a better prognosis. Design : Multicentre retrospective cohort study. Methods : Retrospective chart review. Results: Twenty-one patients were included (9 males, 12 females). Median age at sarcoidosis diagnosis was 48 years (range: 24–68 years). In 14 cases, lymphoma occurred within a previously known sarcoidosis. Five patients received a concomitant diagnosis of sarcoidosis and lymphoma, whereas lymphoma preceded sarcoidosis in two patients. Three patients were diagnosed with Hodgkin’s lymphoma and 18 patients with non-Hodgkin’s lymphoma (diffuse large B-cell lymphoma (DLBCL) ( n = 11), follicular lymphoma ( n = 2), chronic lymphocytic leukemia/small lymphocytic lymphoma ( n = 2), anaplastic large cell lymphoma ALK + ( n = 1), angioimmunoblastic T-cell lymphoma ( n = 1) and T-cell prolymphocytic leukemia ( n = 1)). Thirteen patients were alive and in complete remission. Median age at the time of diagnosis of sarcoidosis was lower in patients with concomitant lymphoma compared with patients with sarcoidosis preceding lymphoma (34 years vs. 51 years, P = 0.01). Patients presenting with DLBCL associated with sarcoidosis were compared with DLBCL without sarcoidosis. No statistical difference was found in the risk of death or progression between the two groups ( P = 0.685). Conclusions: We report here the largest series of lymphoma associated sarcoidosis patients. As opposed to previous studies, we observed a predominance of patients with DLBCL. Our study confirms the concept of the sarcoidosis-lymphoma syndrome. Large B-cell lymphoma does not have a better prognosis when associated with sarcoidosis.

BACKGROUND As lenalidomide (LEN) becomes increasingly established as a standard of care in the treatment (Tx) of newly diagnosed multiple myeloma (NDMM), patients (pts) for whom LEN is no longer a Tx option, including those who have become refractory to LEN, represent a clinical reality. These pts represent the largest population with MM at first relapse in the United States and a growing population globally. To date, they have been poorly studied and remain difficult to treat. Previous trials have demonstrated a clinical benefit with pomalidomide (POM) therapy in LEN-refractory pts with relapsed or refractory MM (RRMM), including those who were heavily pretreated (median of 5 prior regimens) (San Miguel et al. Lancet Oncol 2013; Richardson et al. Blood 2014; Dimopoulos et al. Blood 2016). These studies led to the approval of POM + low-dose dexamethasone (LoDEX) in RRMM. The pomalidomide, bortezomib, and low-dose dexamethasone (PVd) regimen has shown promising activity in early-phase clinical trials in LEN-refractory pts. In the phase 3 OPTIMISMM trial, PVd showed significantly improved progression-free survival (PFS) and a manageable safety profile compared with bortezomib and low-dose dexamethasone (Vd) in intent-to-treat population of pts who received 1-3 prior regimens and were 100% LEN pretreated; 70% of pts were LEN refractory (Richardson et al. ASCO 2018 abstract 8001). Here, we present efficacy and safety results in LEN-refractory and -nonrefractory pts treated at first relapse. METHODS Pts were randomized 1:1 to receive PVd or Vd in 21-day cycles: POM 4 mg/day on days 1-14 (PVd arm only); bortezomib (BORT) 1.3 mg/m2 on days 1, 4, 8, and 11 of cycles 1-8 and on days 1 and 8 of cycles 9+; and DEX 20 mg/day (10 mg/day if aged > 75 yrs) on the days of and after BORT. Key eligibility criteria included ≥ 2 cycles of prior LEN therapy, including LEN-refractory pts. BORT-exposed pts were eligible to enroll, provided they did not have progressive disease during therapy or within 60 days of the last dose of a BORT-containing regimen with BORT dosed at 1.3 mg/m2 twice weekly. The primary endpoint was PFS. RESULTS Out of 559 pts enrolled patients, 226 were treated in the second line (2L), data cut off October 26, 2017: 111 with PVd and 115 with Vd. Median follow-up for 2L pts was 16.4 mos. Among 2L pts, 129 (57.1%) were LEN refractory (64 PVd; 65 Vd) and 97 (42.9%) were LEN nonrefractory (47 PVd; 50 Vd). In LEN-refractory pts (PVd vs Vd) median age was 68.0 vs 69.0 yrs, 57.8% vs 58.5% were male, and 56.3% vs 47.7% had prior BORT. In LEN-nonrefractory pts, median age was 66.0 vs 65.5 yrs, 63.8% vs 38% were male, and 66.0% vs 72.0% had prior BORT. Other key baseline characteristics were similar between Tx arms and subgroups. Median PFS was 17.8 mos with PVd vs 9.5 mos with Vd in LEN-refractory (HR 0.55; 95% CI, 0.33-0.94; Figure 1A) and 22.0 vs 12.0 mos in LEN-nonrefractory pts (HR 0.54; 95% CI, 0.29-1.01; Figure 1B). Response outcomes are shown in Figure 2. ORR was 85.9% with PVd vs 50.8% with Vd in LEN-refractory pts (P < .001) and 95.7% vs 60.0% in LEN-nonrefractory pts (P < .001). In 2L LEN-refractory pts, the most common grade 3 or 4 treatment-emergent adverse events (TEAEs) with PVd vs Vd were neutropenia (35.9% vs 12.9%), thrombocytopenia (17.2% vs 22.6%), and anemia (17.2% vs 8.1%). Grade 3 or 4 infections occurred in 29.7% vs 21.0% of pts. In 2L LEN-nonrefractory pts, the most common grade 3 or 4 TEAEs were neutropenia (36.2% vs 6.3%) and thrombocytopenia (23.4% vs 18.8%). Grade 3 or 4 infections occurred in 27.7% vs 8.3% of pts. In 2L LEN-refractory pts, median Tx duration of PVd vs Vd was 9.7 vs 6.1 mos. In 2L LEN-nonrefractory pts, median Tx duration of Pvd vs Vd was 13.6 vs 6.6 mos. CONCLUSIONS To date, OPTIMISMM is the only phase 3 trial to address Tx of pts with RRMM following LEN exposure in early lines and the first to report data in LEN-refractory pts after first relapse. PVd reduced the risk of progression and death by 45% and 46% vs Vd in LEN-refractory and -nonrefractory pts, respectively. Further, in both subgroups, 2L Tx with PVd significantly improved ORR and led to deeper responses compared with Vd. AEs with PVd therapy were generally consistent with the known AEs of POM, BORT, and DEX. These data further demonstrate that PVd is effective and tolerable in pts for whom LEN is no longer a Tx option, including LEN-refractory pts, supporting its use as 2L therapy in RRMM. Disclosures Dimopoulos: Celgene: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria. Weisel:Amgen, Celgene, Janssen, and Sanofi: Research Funding; Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria; Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Moreau:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Anderson:Celgene: Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau. White:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. San-Miguel:Celgene: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; Roche: Honoraria; BMS: Honoraria; Novartis: Honoraria. Sonneveld:Amgen: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Jenner:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Chugai: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau. Dürig:Janssen: Consultancy, Honoraria; Celgene: Honoraria; Roche: Honoraria, Speakers Bureau. Pavic:AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Salomo:Cilag: Consultancy; Janssen: Consultancy. Yu:Celgene: Employment, Equity Ownership. Nguyen:Celgene Corporation: Employment. Bensmaine:Celgene: Equity Ownership. Peluso:Celgene Corporation: Employment, Equity Ownership. Zaki:Celgene Corporation: Employment, Equity Ownership. Richardson:BMS: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees.

Despite the high prevalence of cancer in the elderly, there is no strong evidence regarding the efficacy of exercise training for reducing debilitating effect of cancer-related fatigue (CRF) and improving quality of life (QoL) in the oncogeriatric population. Hence, the objective of our study is to determine the impact of combined aerobic and resistance training on CRF and QoL in older adults undergoing cancer treatment. A total of 40 older adults (65–80 years) with an ongoing treatment for a curable cancer will be recruited and randomised in two groups: 1) combined training (EX, n=20) and 2) control group (CON, n=20). All variables will be measured before and after 12 weeks of intervention: CRF (FACIT-Fatigue), QoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire), physical capacity (Senior Fitness Test) and body composition (fat and lean body mass, DXA). Our preliminary results show that 12 weeks of mixed exercise training alleviated CRF (ΔEX: -5 vs. ΔCON: -15) and the deterioration of global QoL (ΔEX: -16.7; ΔCON: -41.7). Physical functioning remained stable (ΔEX: 0 vs. ΔCON: -20) and cognitive functioning improved (ΔEX: 33.3 vs. ΔCON: 0), both in EX group only. Finally, lean body mass (ΔEX: +0.5 kg; ΔCON: -3.0 kg) and physical capacity improved in EX while it declined in CON. To conclude, our preliminary results show that combined training is feasible and have a positive impact on CRF and physical capacity. Furthermore, our intervention mitigated the reduction of QoL in older adults undergoing cancer therapy.

Disseminated intravascular coagulation (DIC) is a complex abnormality of hemostasis with dramatic consequences and long described as associated with tumors. Yet the diagnosis and management of paraneoplastic DIC are poorly defined. The purpose of this paper is to review DIC associated with solid tumors, at the pathophysiological and therapeutic levels in particular. We also report data from a recent retrospective series of patients with DIC in the context of a solid tumor, to illustrate the epidemiological, clinical and prognostic.

The link between systemic disease and cancer is not fortuitous. An autoimmune disease can represent the starter for developing a non-Hodgkin lymphoma. This is particularly true for Sjogren's syndrome that is associated with the highest risk of lymphoma (odds ratio up to 44). Other systemic autoimmune diseases concerned are systemic lupus with an odds ratio of 4.5 and rheumatoid arthritis with an odds ratio of 2 to 3. It is now well established that high inflammatory activity, rather than immunosuppressive treatment, is the major risk determinant. The association between solid cancer and autoimmune systemic disease is uncommon and concerns in particular scleroderma and lung cancer. Concerning biotherapy-induced cancers, there is no demonstrated increased risk with anti-TNFα (except for cutaneous carcinoma and maybe melanoma) or with tocilizumab and abatacept even if studies with longer follow-up are needed at least for these two last drugs.

e12588 Background: Within numerous breast cancer types, the neuroendocrine subtype distinguishes itself from the others by its rarity. Most of the actual data comes from European and Asian retrospective studies, whom were mostly published before the 2012 WHO classification. Methods: The aim of our study was to describe a North American cohort of neuroendocrine breast cancer tumors homogenized for the latest WHO classification of 2012. We describe the clinical presentation, diagnostic, therapeutic management and prognosis of our population recensed between 2006 and 2016 at the CHUS in Sherbrooke, Québec. A pathological review of the cases was done to unify the cohort by the latest WHO classification. Results: 59 cases were identified from the 5238 cases of breast cancer evaluated between 2006 and 2016. After review from the pathologist, 9 cases were discarded since they did not meet the diagnostic criterias. 47 patients had invasive breast carcinoma with neuroendocrine differentiation, 4 patients had poorly differentiated/small cell carcinoma and none had well differentiated neuroendocrine tumor. 44 patients were not metastatic whereas 7 patients were metastatic at disease onset with a mean age at diagnosis of 70 and 67 years respectively. 10% (4/44) developed a metastatic disease with a median time of 30 months. The mean size of the tumor was 26,1 mm and had a mean Ki67% of 28,3%. All of our patients were ER+, 98% PR+ and 4% Her2+. None had a triple negative disease. 6 patients were SBR grade 1, 31 were grade 2 and 12 were grade 3. The median follow-up for the non-metastatic patients was 42 months and 23 months for the metastatic patients. The median overall survival of our metastatic cohort was 30 months. The histologic subtype did not statistically influence the overall survival and the progression-free survival. Conclusions: Our study is the largest North American cohort of neuroendocrine breast cancer tumors classified with the latest WHO classification of 2012. More details about each subgroup analysis will be presented at the meeting. Even with this classification, the histologic diagnosis remains challenging. Further studies are needed to better characterize these patients and define their optimal management.

Background:Cost-utility analysis (CUA) is becoming more commonly used in healthcare decision-making. CUA uses the quality-adjusted life-years (QALY) metric, which combines the length of life with the health-related quality of life (HRQoL). Most QALY-measuring instruments were validated for g