Six-month Overall Survival Research Articles

Glofitamab combined with poseltinib and lenalidomide for relapsed/refractory diffuse large B cell lymphoma: Interim analysis of GPL study.

7066 Background: Despite advanced treatments, including chimeric antigen receptor therapy (CAR-T), a significant proportion of patients succumb to relapsed and refractory diffuse large B cell lymphoma (R/R DLBCL). In vitro experiments suggest synergism between BTK inhibitor (BTKi) and T-cell engager, we initiated a multicenter trial of poseltinib and glofitamab in combination with lenalidomide in R/R DLBCL. Methods: This is a phase II, open label, single arm study aiming to enroll 76 participants with adult R/R DLBCL patients (NCT05335018). Patients refractory to frontline therapy or those who failed more than two lines of therapies were enrolled. Previous anti-CD19 CAR-T was allowed, while previous CD20 T-cell engager was not permitted. Participants received glofitamab (In cycle 1, dose is increased weekly from 2.5mg to 10mg, and after cycle 2, 30mg is administered on Day 1), lenalidomide (20mg daily from Day 1-14), and poseltinib (40mg twice daily from Day 1-21) (GPL) every 3 weeks for a total of 12 cycles(induction). Maintenance with poseltinib and lenalidomide for 17 cycles were given to patients after induction period. The primary endpoint is overall response rate (ORR), with secondary endpoints including duration of response (DoR), complete response rate (CRR), progression free survival (PFS), overall survival (OS), and incidence of treatment related adverse events. Results: No safety signals were observed in the safety cohort (n=6, 3+3 design). As of November 2023, 37 patients (median age 71) have been treated with GPL, with a median follow up duration of 3.6 months. In prior lines of therapy, 13 patients (35.1%) received treatment more than 2, and 26 patients (70.3%) were with Ann Arbor stage III/IV and 7 patients (18.9%) were refractory to frontline treatment. Previously, 3 patients (8.1%) received CAR-T. Out of 28 evaluable patients, ORR was 89.3%, with CRR of 42.9%. Six-month OS and PFS rate were 81% and 55%. DoR at 6 months was 66%. Neutropenia (45.9%) was the most common grade(gr) 3-4. Three patients (8.1%) died of gr5. There was 1 case (2.7%) of gr3 atrial fibrillation and gr1 bleeding. No incidence of gr3 or above liver/renal toxicity were observed. Overall, 3 patients (8.1%) discontinued GPL treatment due to toxicity, and cytokine release syndrome was observed in 7 patients (18.9%) and only 2 patients (5.4%) were gr3-4. Conclusions: Interim analysis indicates that the GPL regimen is an effective and safe regimen for R/R DLBCL patients. High response rates observed support further investigation of GPL for potential synergism between T-cell engagers and BTKi. This multicenter study is actively recruiting patients and is set to complete enrollment within this year. Clinical trial information: NCT05335018 . [Table: see text]

Lurbinectedin in small cell lung cancer: real-world experience of a multicentre national early access programme.

Lurbinectedin is a novel oncogenic transcription inhibitor active in several cancers, including small cell lung cancer (SCLC). We aimed to describe the first Australian experience of the clinical efficacy and tolerability of lurbinectedin for the treatment of SCLC after progression on platinum-containing therapy. Multicentre real-world study of individuals with SCLC initiating lurbinectedin monotherapy (3.2 mg/m2 three-weekly) on an early access programme between May 2020 and December 2021. Key outcomes were clinical utilisation, efficacy and tolerability. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Outcome data were collected within the AUstralian Registry and biObank of thoRacic cAncers (AURORA). Data were analysed for 46 individuals across seven sites. Lurbinectedin was given as second- (83%, 38/46) or subsequent- (17%, 8/46) line therapy, mostly with prior chemoimmunotherapy (87%, 40/46). We report dose modifications (17%, 8/46), interruptions/delays (24%, 11/46), high-grade toxicities (28%, 13/46) and hospitalisations (54%, 25/46) during active treatment. The overall response rate was 33% and the disease control rate was 50%. Six-month OS was 44% (95% confidence interval (CI): 29.0-57.1). Twelve-month OS was 15% (95% CI: 6.5-26.8). From lurbinectedin first dose, the median PFS was 2.5 months (95% CI: 1.8-2.9) and OS was 4.5 months (95% CI: 3.5-7.2). From SCLC diagnosis, the median OS was 12.9 months (95% CI: 11.0-17.2). Individuals with a longer chemotherapy-free interval prior to lurbinectedin had longer PFS and OS. This real-world national experience of lurbinectedin post-platinum chemotherapy and immunotherapy for individuals with SCLC was similar to that reported in clinical trials.

Absolute Lymphocyte Count and Outcomes of Multiple Myeloma Patients Treated with Idecabtagene Vicleucel: The U.S. Myeloma CAR T Consortium Real World Experience

Introduction: Chimeric Antigen Cell (CAR) T-cell therapy with idecabtagene vicleucel (ide-cel) is FDA approved for relapsed refractory multiple myeloma (MM). Investigating factors that may predict response, toxicity and survival is important to guide therapy and inform prognosis. Low pre-lymphodepletion (LD) absolute lymphocyte count (ALC) was found to be associated with worse outcomes in a small cohort of patients (pts) treated with ide-cel (Liu et al. Transplant Cell Ther 2022). We evaluated the impact of pre-apheresis (pre-A) and pre-LD peripheral blood ALC on post-ide-cel outcomes in a large patient cohort. Methods: A total of 215 myeloma pts were treated with ide-cel at 11 U.S. academic medical centers. We studied the effect of ALC including pre-A, pre-LD, absolute and percent reduction in ALC between apheresis and LD on progression free survival (PFS), overall survival (OS), overall hematologic response rate (ORR which included VGPR, CR and sCR) and cytokine release syndrome (CRS) incidence. Associations of ALC parameters with PFS and OS were evaluated using Kaplan-Meier (KM) method and Cox proportional hazard model. Patient demographics and clinical characteristics between ALC groups were compared using Chi square test and Wilcoxon rank test. Results: The median patient age was 64 years (range, 36-83) and 60 % were male. The median prior lines of therapy was 6 (IQR, 5-9), 84.2% had a prior autologous hematopoietic cell transplant (AHCT), 44.7% had extramedullary disease, and 77.1% received bridging therapy (BT). CRS was seen in 81.1% of the pts, mostly grade 1. The median pre-A and pre-LD ALC's were 0.65 x109/L (range, 0.06-5.3) and 0.55 (range, 0-5.0), respectively. The pre-A ALC was significantly higher than pre-LD ALC (mean difference and 95% CI: 0.10 (0.04, 0.40), p=0.002). The median follow-up time after CAR-T infusion was 5.4 (IQR, 2.1-8.3) months. Pre-A and pre-LD ALC's were not significantly associated with PFS or OS, while pts with a high absolute reduction in ALC between apheresis and LD (≥0.27 or top quartile) had a significantly worse six-month PFS (48.4 vs 63.5%, p= 0.04) and OS (76.0 vs 87.7%, p= 0.03). Similarly, patients with a high percent reduction between pre-A and pre-LD ALC (≥37.5% or top quartile) had a worse six-month PFS (41.9 vs 65%, p <0.001) and OS (70.5 vs 89%, P=0.001). PFS and OS differences remained statistically significant after adjusting for age, race, CRS grade, ECOG-PS, extramedullary disease and prior AHCT. Kaplan-Meier estimated PFS and OS curves for absolute ALC reduction groups and percent ALC reduction groups are displayed in Figure 1. The one-month and three-month ORR, and CRS grade were not significantly different between pre-A (≥1 or <1), pre-LD (≥1 or <1), absolute reduction and percent reduction ALC groups. ECOG-PS ≥2 (p= 0.004), ISS III (p= 0.015), and implementation of BT (p <0.01) were found to be associated with high ALC reduction or percent reduction. There was no difference in ALC between pts who received BT vs not. However, more patients in the high ALC reduction (>=0.27: 90.4% vs 72.6%, p=0.008) and high ALC percent reduction (>=37.5: 96.2% vs 70.5%) groups received BT. Moreover, pts who received BT had a worse PFS (six-month PFS: 53.2% vs 85.3%, p <0.001) and OS (six-month OS: 81.9% vs 95.8%, p= 0.02) likely indicating aggressive disease biology. The specific types of BT were not available in our dataset. Conclusion: Pre-apheresis ALC did not impact survival in this large cohort of myeloma patients treated with ide-cel. Reduction in ALC between apheresis and lymphodepletion is a potentially predictive tool of survival outcomes and may be associated with more aggressive disease biology and the need for more aggressive bridging therapy. Investigating the association between specific types of bridging therapy, ALC reduction and outcomes may guide clinical decision making in this heavily pretreated myeloma patient population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Novel Agents May be Preferable to Chemotherapy for Large B-Cell Lymphoma Progressing after CD19-CAR-T: A Multicenter Observational Study

Novel Agents May be Preferable to Chemotherapy for Large B-Cell Lymphoma Progressing after CD19-CAR-T: A Multicenter Observational Study

Institutional outcomes of whole brain radiotherapy for metastatic melanoma brain metastases.

e14504 Background: The management of melanoma with multiple brain metastases (MBM) is complex given improvements in targeted agents, immunotherapy, and radiotherapy. Whole brain radiation therapy (WBRT) is a radiotherapy technique with limited outcomes data. We report our institutional outcomes for MBM patients receiving WBRT and assess whether certain clinical factors impact prognosis. Methods: A retrospective review of a single institution database was performed. Patients diagnosed with MBM from 2000-2018 treated with WBRT, with or without systemic treatments, were included. Post-WBRT brain MRI scans were assessed at timed intervals for radiographic response. Clinical and treatment variables associated with overall survival (OS), progression free survival (PFS), intracranial failure-free survival (IFFS), and local failure-free survival (LFFS) were assessed. Data was collected on radiation-induced side effects, including radionecrosis, hemorrhage, and memory deficits. Results: Of 1347 patients treated with WBRT from 2000-2018, 63 patients had melanoma. 69% of patients had ≥5 brain metastases at the time of WBRT, 68% had extracranial disease, and 71% received steroids during their overall treatment course. Most had received previous therapies and had WBRT as a last resort. Median WBRT dose was 30 Gray over 10 fractions. Median follow-up was 4.0 months. Six-month OS, PFS, IFFS, and LFFS were 52.7%, 20.4%, 52.3%, and 43%. Median OS, PFS, IFFS, and LFFS were 7.0 months, 2.2 months, 6.1 months, and 4.9 months. Performance status correlated with OS on univariate and multivariate analysis. BRAFi was the only systemic therapy to significantly impact OS on univariate analysis (HR 0.24, 95% CI 0.07-0.79, p = 0.019), although this was not seen on multivariate analysis. There was a 19% rate of memory deficits. Among the 46 patients with post-WBRT brain scans, 17% had radionecrosis and 28% had intralesional hemorrhage. Not all radiographically noted radiotoxicities were clinically significant, although hemorrhage decreased IFFS on both univariate and multivariate analysis. Conclusions: Outcomes for MBM patients receiving WBRT indicate that WBRT remains a worthy option to control intracranial disease. Treatment-related effects such as hemorrhage, necrosis, or cognitive changes are considerations. Median PFS and IFFS suggest that systemic disease control continues to be the greater issue. The role of WBRT should be re-evaluated in the modern era, which features advanced imaging detection ability, newer systemic agents, and improved steroid avoidance strategies.

Survival of patients with non-small cell lung cancer having leptomeningeal metastases treated with immune checkpoint inhibitors

IntroductionPatients with non-small cell lung cancer (NSCLC) experience leptomeningeal metastases (LM) in 3–9% of cases. Because overall survival (OS) and performance status are very poor, they are mostly excluded from clinical trials. Here, we evaluated survival of patients with NSCLC having LM treated with immune checkpoint inhibitors (ICIs). MethodsA prospectively collected list of patients with advanced NSCLC treated with ICIs between November 2012 and July 2018 in 7 European centres was merged. All patients with LM before ICI start were selected, data were retrospectively added and patients were classified according to the National Comprehensive Cancer Network (NCCN) LM prognostic classification (good/poor). Progression-free survival (PFS) and OS on ICIs were evaluated. ResultsNineteen of 1288 (1.5%) patients had LM; 73.7% had synchronous brain metastases; 73.7% had neurological symptoms at the start of ICIs and 52.6% were in the NCCN LM good prognosis group. Programmed death ligand-1 (PD-L1) expression was known for 42.1% of patients (87.5% positive). Median follow-up was 13 months from the start of ICIs, and median (95% confidence interval [CI]) PFS on ICIs was 2.0 (1.8–2.2) months. Six-month PFS rate was 21.0% and was significantly higher in the NCCN good versus poor prognostic group: 40% vs 0% (p = 0.05). Twelve-month PFS rate was 0%. Median (95% CI) OS from the start of ICIs was 3.7 (0.9–6.6) months. Six-month OS rate was 36.8%, and 12-month OS rate was 21.1%; both were not statistically significantly different for the good versus poor NCCN prognostic group (p = 0.40 and p = 0.56, respectively). ConclusionSome patients with NSCLC having LM do benefit from ICI treatment; specifically, those in the NCCN LM good prognosis group can obtain a long survival.

A new instrument for predicting survival of patients with cerebral metastases from breast cancer developed in a homogeneously treated cohort.

BackgroundPrevious survival scores for breast cancer patients with cerebral metastases were developed in cohorts receiving heterogeneous treatments, which could have introduced selection biases. A new instrument (WBRT-30-BC) was created from 170 patients receiving whole-brain radiotherapy (WBRT) alone with 30 Gy in 10 fractions.MethodsCharacteristics showing significant associations (p < 0.05) with overall survival (OS) or a trend (p < 0.08) on multivariate analysis were used for the WBRT-30-BC. For each characteristic, 6-month OS rates were divided by 10. These scoring points were added for each patient (patient scores). The WBRT-30-BC was compared to the diagnosis- specific graded prognostic assessment (DS-GPA) classification and Rades-Score for breast cancer regarding positive predictive values (PPVs) to identify patients dying within 6 months and patients surviving at least 6 months following WBRT.ResultsOn multivariate analysis, Karnofsky performance score (KPS) was significant (risk ratio [RR]: 2.45, p < 0.001). In addition, extra-cerebral metastatic disease (RR: 1.52, p = 0.071) and time between breast cancer diagnosis and WBRT (RR: 1.37, p = 0.070) showed a trend. Based on these three characteristics, four predictive groups were designed: 7–9, 10–12, 13–15 and 16 points. Six-month OS rates were 8%, 41%, 68% and 100% (p < 0.001). PPVs to identify patients dying within 6 months were 92% (WBRT-30-BC), 84% (DS-GPA) and 92% (Rades-Score). PPVs to identify patients surviving for at least 6 months were 100% (WBRT-30-BC), 74% (DS-GPA) and 68% (Rades-Score).ConclusionsThe WBRT-30-BC appeared very accurate in predicting death ≤ 6 months and survival ≥ 6 months of breast cancer patients receiving WBRT. It was superior to previous instruments in predicting survival ≥ 6 months.

Real-world efficacy and safety of liposomal irinotecan plus fluorouracil/leucovorin in patients with metastatic pancreatic adenocarcinoma: a study by the Korean Cancer Study Group.

Background:Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) was effective and well-tolerated in patients with metastatic pancreatic adenocarcinoma (mPAC) that progressed on gemcitabine-based therapy in the global NAPOLI-1 trial. Real-world data may further clarify the outcomes and safety profile of nal-IRI + 5-FU/LV in clinical practice.Methods:This retrospective analysis included patients with mPAC who received nal-IRI + 5-FU/LV following gemcitabine-based therapy under a Managed Access Program in Korea.Results:From January 2017 to April 2018, 86 patients across 10 institutions received nal-IRI + 5-FU/LV (median age, 61 years; 60% male; ECOG performance status, 0–1). A total of 35 (41%) and 51 (59%) patients had received less than two and two or more lines of chemotherapy before inclusion, respectively. At a median follow up of 6.4 months, median overall survival (OS) was 9.4 months (95% confidence interval [CI] 7.4–11.4) and median progression-free survival (PFS) was 3.5 months (95% CI 1.3–5.7). Six-month OS and PFS rates were 65.1% and 37.5%, respectively. Objective response and disease control rates were 10% and 55%, respectively. Most common grade 3–4 toxicities were neutropenia (37.2%), nausea (10.5%), vomiting (9.3%), anorexia (8.1%) and diarrhoea (4.7%).Conclusion:Real-life data for Korean patients indicate that, consistent with NAPOLI-1, nal-IRI + 5-FU/LV is effective and well-tolerated in patients with mPAC that progressed on gemcitabine-based therapy.

1309P - Efficacy and safety of necitumumab and pembrolizumab combination therapy in patients with stage IV non-small cell lung cancer (NSCLC)

Background: Studies of EGFR-directed monoclonal antibody (mAb) necitumumab (neci) and anti-PD1 pembrolizumab (pembro) demonstrate activity of each agent in NSCLC. Methods: This phase 1b, multicenter, single arm study of neci and pembro examined the safety, efficacy, and tolerability in pretreated patients with Stage IV NSCLC (NCT02451930). PDL1 was centrally assessed retrospectively using IHC 22C3 pharmDx assay (negative, weak positive, strong positive if < 1%, 1-49%, ≥50% of tumor cells were stained, respectively). Escalating doses of neci 600 – 800 mg IV (days 1 and 8 every 3 weeks [Q3W]) were administered with pembro (200 mg IV) on Day 1 Q3W (Part A). Established dose from Part A was used in the expansion cohort (Part B). Study objectives were to determine the dose-limiting toxicity (DLT) and evaluate tolerability and overall response rate (ORR) by RECIST 1.1. Secondary objectives included progression-free survival (PFS) and overall survival (OS). Results: for 64 patients are reported. Part A completed without DLTs (9 patients; 2 squamous, 7 nonsquamous). Overall, 3 patients received neci 600 mg and 61 patients received neci 800 mg; all patients received pembro 200 mg. ORR (95% CI) was 23.4% (13.8, 35.7). Median PFS (95% CI) was 4.1 m (2.4, 6.9). Six-month OS rate (95% CI) was 74.7% (61.5, 83.9). Treatment-emergent adverse events occurring in ≥ 20% of all patients (n (%)) included dermatitis acneiform: 43 (67.2); asthenia: 24 (37.5); dry skin: 23 (35.9); hypomagnesemia: 21 (32.8); fatigue: 20 (31.3); decreased appetite and diarrhea (each): 17 (26.6); headache, pruritus, and stomatitis (each): 14 (21.9). Two neci 800 mg + pembro patients experienced grade 5 respiratory tract infection. Conclusions: The results suggest modest activity of the combination in a NSCLC patient population with a relatively high proportion of PDL1 negative tumors (Table).Table1309PNecitumumab 600 mg/800 mg + Pembrolizumab 200 mgOverallSquamousNonsquamous(N = 64)(n = 30)(n = 34)Age, median (range), y65 (43, 81)67.5 (48, 81)61 (43, 75)Male, n (%)46 (71.9)23 (76.7)23 (67.6)Prior systemic therapy, n (%)1 line36 (56.3)22 (73.3)14 (41.2)2 lines15 (23.4)5 (16.7)10 (29.4)≥3 lines13 (20.3)3 (10.0)10 (29.4)Baseline ECOG PS, n (%)64 (100)30 (100)34 (100)017 (26.6)3 (10.0)14 (41.2)146 (71.9)26 (86.7)20 (58.8)21 (1.6)1 (3.3)0Tobacco use, n (%)64 (100)30 (100)34 (100)Former41 (64.1)21 (70.0)20 (58.8)Current14 (21.9)7 (23.3)7 (20.6)Never9 (14.1)2 (6.7)7 (20.6)EfficacyORR n (%) (95% CI)15 (23.4) (13.8, 35.7)6 (20.0) (7.7, 38.6)9 (26.5) (12.9, 44.4)mPFS (months) (95% CI)4.1 (2.4, 6.9)2.8 (1.4, 5.5)6.9 (2.7, 12.3)6-month OS rate (%) (95% CI)74.7 (61.5, 83.9)63.6 (42.8, 78.6)84.2 (66.0, 93.1)PDL1 Status64 (100)30 (100)34 (100)PDL1 negative32 (50.0)13 (43.3)19 (55.9)ORR n (%) (95% CI)4 (12.5) (3.5, 29.0)1 (7.7) (0.2, 36.0)3 (15.8) (3.4, 39.6)mPFS (m) (95% CI)2.69 (1.4, 4.1)6-month OS rate (%) (95% CI)68.2 (47.7, 82.0)PDL1 Weak positive12 (18.8)7 (23.3)5 (14.7)ORR n (%) (95% CI)3 (25.0) (5.5, 57.2)1 (14.3) (0.4, 57.9)2 (40.0) (5.3, 85.3)mPFS (m) (95% CI)5.4 (0.8, –)6-month OS rate (%) (95% CI)83.3 (48.2, 95.6)PDL1 Strong positive10 (15.6)5 (16.7)5 (14.7)ORR n (%) (95% CI)4 (40.0) (12.2, 73.8)2 (40.0) (5.3, 85.3)2 (40.0) (5.3, 85.3)mPFS (m) (95% CI)7.6 (1.0, 12.3)6-month OS rate (%) (95% CI)80.0 (40.9, 94.6)Unknown10 (15.6)5 (16.7)5 (14.7)ORR n (%) (95% CI)4 (40.0) (12.2, 73.8)2 (40.0) (5.3, 85.3)2 (40.0) (5.3, 85.3)mPFS (m) (95% CI)– (0.82, –)6-month OS rate (%) (95% CI)78.8 (38.1, 94.3)ECOG PS, Eastern Cooperative Oncology Group performance status; PDL1, programmed death ligand 1; ORR, overall response rate; mPFS, median progression-free survival; OS, overall survival; CI, confidence interval. Open table in a new tab ECOG PS, Eastern Cooperative Oncology Group performance status; PDL1, programmed death ligand 1; ORR, overall response rate; mPFS, median progression-free survival; OS, overall survival; CI, confidence interval. Clinical trial identification: NCT02451930 Legal entity responsible for the study: Eli Lilly and Company Funding: Eli Lilly and Company Disclosure: B. Besse: Research grants from Eli Lilly and Company and Merck, Sharp & Dohme. P. Garrido Lopez: Personal fees from BMS, Novartis, Pfizer, Roche, MSD, Guardant, and Abbvie; and grants and personal fees from BI. A. Cortot: Personal fees from Lilly and MSD; personal fees and non-financial support from Roche, Novartis, Astra-Zeneca, and Pfizer; and grants, personal fees, and non-financial support from Boehringer-Ingelheim. M. Perol: Personal fees from Eli Lilly and MSD. M. Gil: Employee of Eli Lilly and Company and owns Eli Lilly stock. Dr. Gil has a patent Combination Therapy for cancer pending to Eli Lilly. G. Chao: Employee of Eli Lilly and Company. J. Shahidi: Employee and stock owner of Eli Lilly and Company. J. Bennouna: Personal fees from Roche, Boehringer-Ingelheim, BMS, and Astra-Zeneca. All other authors have declared no conflicts of interest.

A New Scoring Tool to Assess Overall Survival in Patients With Intracerebral Metastases From Gynecological Cancers.

This study aimed to facilitate individualized treatment strategies for intracerebral metastases from gynecological cancers by creating a specific overall survival (OS) score. Fifty-six patients irradiated for cerebral metastases from gynecological cancers were included. Eleven factors were retrospectively analyzed for OS: age, Eastern Cooperative Oncology Group (ECOG) performance score, cancer type, histology, histologic grading, initial stage, number of lesions, extracerebral metastases, time between cancer diagnosis and brain metastases treatment, recursive partitioning analysis class, and type of treatment. Independent predictors of OS were incorporated in the score (better OS, 1 point; worse OS, 0 points). On Cox proportional hazards analysis, performance score (hazards ratio, 1.98; 95% confidence interval, 1.30-3.23; P = 0.001), no extracerebral metastases (3.34; 1.46-8.96; P = 0.003), and recursive partitioning analysis class 1 (3.27; 1.97-5.65; P < 0.001) were significant. The following points were assigned: ECOG score 1 to 2 = 1 point, ECOG score 3 to 4 = 0 points, no extracerebral metastases = 1 point, extracerebral metastases = 0 points. Sum scores were 0 (n = 32), 1 (n = 15), or 2 points (n = 9). Six-month OS rates were 6%, 67%, and 100%, respectively (P < 0.001). A predictive tool including 3 groups with significantly different OS probabilities was designed for patients with cerebral metastases from gynecological cancers. This tool will aid in choosing individual treatments.

Clinical activity of PD1/PDL1 inhibitors in metastatic non-clear cell renal cell carcinoma (nccRCC).

482 Background: PD1/PDL1 inhibitors have shown significant activity in the treatment of patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC), but their activity in nccRCC is poorly characterized. Methods: We conducted a retrospective multicenter study of pts with metastatic nccRCC treated with PD1/PDL1 inhibitors. Baseline clinical parameters, overall response rate (ORR) by RECIST, time-to-treatment failure (TTF), and overall survival (OS) were summarized. Results: We identified 40 pts across 8 academic institutions. Fourteen (35%) had papillary histology, 10 (25%) chromophobe, 3 (8%) translocation, and 7 (18%) unclassified. Six (16%) had ccRCC with a sarcomatoid component &gt; 30%. 20% had International Metastatic RCC Database Consortium (IMDC) favorable-risk disease, 60% intermediate, and 20% poor-risk. Ten (25%) were treatment-naïve and the majority received PD1/PDL1 monotherapy (n=30, 75%), while the remaining received a combination of PD1/PDL1 with anti-VEGF(R) or anti-CTLA4 therapy. ORR for the total cohort was 18% and 10% for PD1/PDL1 monotherapy pts (Table). With a median follow-up of 5.6 months, the overall median TTF was 4.7 months (2.9-15.9) and six-month OS was 81% (60-91%). Conclusions: PD1/PDL1 blockade resulted in some activity in pts with various nccRCC histologies. In the absence of available clinical trials, this data may support the use of PD1/PDL1 blocking agents in pts with nccRCC. [Table: see text]

Rechallenge temozolomide in glioma: A case series from India

Temozolomide (TMZ) is an integral part of upfront treatment of high-grade gliomas. It is administered postsurgery as concurrent therapy with radiation and subsequently as adjuvant chemotherapy for 6-12 cycles. It is unknown whether rechallenge of salvage TMZ in previously treated high-grade glioma has any efficacy. Patients treated with salvage rechallenged TMZ between January 2015 and August 2016 were included for this retrospective analysis. SPSS version 20 was used for this analysis. Time to event analysis was performed using the Kaplan-Meier method. Progression-free survival (PFS) and overall survival (OS) were estimated. The maximum grade of toxicity was noted in accordance with CTCAE version 4.02. A total of 23 patients were selected for analysis with the median age being 43 years (range: 26-69 years). The tumor histopathology at baseline was astrocytoma Grade 2 in 1 patient, oligodendroglioma Grade 2 in 3 patients, anaplastic astrocytoma in 7 patients, anaplastic oligodendroglioma in 2 patients, and glioblastoma in 10 patients. All of them had previously received TMZ. The median numbers of previous TMZ cycles received were 6 (4-18). The median time to failure postlast treatment was 24 months (5-72 months). The median number of cycles of rechallenged salvage TMZ administered was 6 cycles (range: 1-18). Grade 3-4 myelosuppression was seen in 3 patients (13.4%). The median PFS was 459 days (95% confidence interval: 212.1-705.9). The median OS was 25 months. Six-month OS and 1-year OS were 81.4% and 75.1%, respectively. Rechallenge with TMZ in recurrent glioma that had previously responded to TMZ is associated with improvement in PFS and OS and has a sufficiently long disease-free interval.

Acute Myeloid Leukemia in Elderly Patients: Experience of the Antoine Lacassagne Center and a New Score to Define Fit Patients

Management of Acute Myeloid Leukemia (AML) in the elderly is particularly difficult as life expectancy is highly variable and the benefit-risk ratio of treatment depends on comorbidities and age-related pharmacological specificities.Objective:To define the prognostic factors for overall survival (OS) and complete remission (CR) and establish a feasible and efficient new prognostic scoring system to assist clinicians in an age-adapted treatment strategy.Methods:From January 2000 to December 2014, 163 patients (pts) presenting an AML in a French regional cancer center in Nice were retrospectively analyzed. According to functional status, patients were treated with induction chemotherapy, azacitidine or palliative care. Complete remission rate (CR) and early-death rate were calculated. Six-month, 1-year and 2-year overall survival (OS) were analyzed with the Kaplan-Meier method and log-rank test. Univariate and multivariate logistic regression analyses were done and a p-value <0.1 and 0.05, respectively, were considered statistically significant.Population:From January 2000 to December 2014, 163 pts ³ 65 years were included; median age was 73.3 years (65-94.6), with 94 men (57.7%). PS was 0, 1, 2, 3 or 4 for 33 pts (20.3%), 77 pts (47.2%), 22 pts (13.5%), 20 pts (12.3%) and 6 pts (3.7%), respectively. Modified Charlson Score (calculated without considering age and leukemia criteria) was 0-1 and ³2 for 83 pts (50.9%) and 77 pts (47.2%), respectively. Secondary AML represented 44.2% of this elderly population. Induction chemotherapy was either full-dose cytarabin-daunorubicin 3+7, or cytarabin-idarubicin or cytarabin-clofarabine. Palliative care consisted of hydroxyurea and etoposid chemotherapy and best supportive care. Then, 112 pts (68.7%), 21 pts (12.9%) and 30 pts (18.4%) were treated with induction chemotherapy, azacitidine and palliative care, respectively. Among the 112 pts (68.7%) induced, 56 pts (35.9%) reached CR, 42 pts (25.8%) with a first induction and 14 pts (10.1%) with salvage chemotherapy. Otherwise, 39 pts (23.9%) ended up relapsing. Taking into account the entire treatment, 42 pts (25.8%) received azacitidine.Results:The 6-month, 1-year and 2-year OS for the entire cohort of 163 patients were 64.3%, 46.7% and 24.4%, respectively. Administration of induction chemotherapy was significantly predictive of CR (50% vs 2.0%, p<0.001) and almost predictive of 2-year OS (29% vs 12.5%, p=0.07). With or without induction chemotherapy, early-death rate (<8 weeks) was 12.5% and 37.3%, respectively. Thus, induction remained the best treatment for physically-fit elderly patients. Using azacitidine at any time of the treatment was a predictive factor of longer survival (1-year OS: 67.8% vs 36.9%, p=0.004). Otherwise, no impact was found on 2-year OS (25.6% vs 25.9%, NS). We tried to define a prognostic score to select elderly patients likely to benefit from induction chemotherapy. In univariate analysis, the significant prognostic factors of OS in the elderly population treated with induction chemotherapy was: age³ 75, unfavorable karyotype, creatinine clearance using the MDRD equation< 60ml/min/1.73m2, Modified Charlson Score ³2 and PS³2. In a multivariate analysis, only Charlson score and PS remained significant in terms of OS. Patients with Charlson Score ²1 and PS ²1 (0 unfavorable factor, n=60) or Charlson Score ³2 or PS ³2 (1 unfavorable factor, n=69) were considered to be at low risk (fit) for induction chemotherapy whereas patients with Charlson Score ³2 and PS³2 (2 unfavorable factors, 29 pts) were considered to be at high risk (frail). In the entire cohort (n=158 pts, data missing for 5 pts), Fit patients and Frail patients had an early-death rate of 10.8% vs 30.8% (p=0.048), a CR rate of 40.3% vs 3.8% (p<0.001), six-month OS 69.7% vs 39%, 1-year OS 53.7% vs 0% and 2-year OS 28.8% vs 0% (p<0.001), respectively. No survivors were observed in the frail group after one year of follow-up. Sub-group analysis found the same results for patients initially treated with induction chemotherapy or palliative treatment.Conclusion:We present a prognostic model composed of two easy-to-operate parameters that stratify patients into Fit or Frail groups. Patients with a Modified Charlson Score ³2 and a PS ³2 did not benefit from induction chemotherapy and had a high risk of death. In such cases, treatment should be azacitidine or palliative treatment. External validation is needed. [Display omitted] DisclosuresNicolini:Novartis: Honoraria, Other: Consulting & Advisory Role, Research Funding, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting or Advisory Role, Speakers Bureau; ARIAD: Honoraria, Research Funding, Speakers Bureau; BMS: Other: Travel/Accommodations/Expenses; Novartis: Other: Travel, Accommodations, Expenses.

Topotecan for Relapsed Small-cell Lung Cancer: Systematic Review and Meta-Analysis of 1347 Patients.

Topotecan is the most reliable chemotherapy regimen for relapsed small-cell lung carcinoma (SCLC). The efficacy and adverse effects of topotecan as reported by previous studies varied greatly. The inclusion criterion was a prospective study that was able to provide data for 6-month over-all survival (OS) rate, 1-year OS rate, objective responses, and/or adverse effects of single agent topotecan as a second line chemotherapy for SCLC, written in English language as a full article. Any topotecan regimen were allowed. Binary data were meta-analyzed with the random-model generic inverse variance method. We included 14 articles consisted of 1347 patients. Pooled values were estimated as follows. <Refractory relapse> Six-month OS rate: 37% (95% CI: 28–46%). One-year OS rate: 9% (95% CI: 5–13%). Response rate: 5% (95% CI: 1–8%). <Sensitive relapse> Six-month OS rate: 57% (95% CI: 50–64%). One-year OS rate: 27% (95% CI: 22–32%). Response rate: 17% (95% CI: 11–23%). <Adverse effect> Grade III/IV neutropenia 69% (95% CI: 58–80%). Grade III/IV thrombopenia 41% (95% CI: 34–48%). Grade III/IV anemia 24% (95% CI: 17–30%). Non-hematorogical events were rare. Chemotherapy-related death 2% (95% CI: 1–3%). In conclusion, Topotecan provided a possibly promising outcome for sensitive-relapse SCLC and poor outcome for refractory relapse SCLC. Adverse events were mainly hematological.