scholarly journals Evaluation of RAPNO criteria in medulloblastoma and other leptomeningeal seeding tumors using MRI and clinical data

2020 ◽  
Vol 22 (10) ◽  
pp. 1536-1544 ◽  
Author(s):  
Jian Peng ◽  
Hao Zhou ◽  
Oliver Tang ◽  
Ken Chang ◽  
Panpan Wang ◽  
...  
Keyword(s):  
Clinical Data ◽  
Interobserver Agreement ◽  
Proportional Hazards ◽  
Objective Response ◽  
Choroid Plexus Papilloma ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Cox Proportional Hazards ◽  
Treatment Modalities ◽  
Leptomeningeal Seeding

Abstract Background Although the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group has made recommendations for response assessment in patients with medulloblastoma (MBL) and leptomeningeal seeding tumors, these criteria have yet to be evaluated. Methods We examined MR imaging and clinical data in a multicenter retrospective cohort of 269 patients with MBL diagnoses, high grade glioma, embryonal tumor, germ cell tumor, or choroid plexus papilloma. Interobserver agreement, objective response (OR) rates, and progression-free survival (PFS) were calculated. Landmark analyses were performed for OR and progression status at 0.5, 1.0, and 1.5 years after treatment initiation. Cox proportional hazards models were used to determine the associations between OR and progression with overall survival (OS). Subgroup analyses based on tumor subgroup and treatment modality were performed. Results The median follow-up time was 4.0 years. In all patients, the OR rate was .0.565 (95% CI: 0.505–0.625) by RAPNO. The interobserver agreement of OR determination between 2 raters (a neuroradiologist and a neuro-oncologist) for the RAPNO criteria in all patients was 83.8% (k statistic = 0.815; P < 0.001). At 0.5-, 1.0-, and 1.5-year landmarks, both OR status and PFS determined by RAPNO were predictive of OS (hazard ratios [HRs] for 1-year landmark: OR HR = 0.079, P < 0.001; PFS HR = 10.192, P < 0.001). In subgroup analysis, OR status and PFS were predictive of OS for all tumor subtypes and treatment modalities. Conclusion RAPNO criteria showed excellent consistency in the treatment response evaluation of MBL and other leptomeningeal seeding tumors. OR and PFS determined by RAPNO criteria correlated with OS.

Differential response rates in early-phase cancer clinical trials (EPCCT).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3133-3133
Author(s):  
Rozana Abdul Rahman ◽  
Neethu Billy Graham Mariam ◽  
Hitesh Mistry ◽  
Sreeja Aruketty ◽  
Matt Church ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response Rates ◽  
Primary Objective ◽  
Cox Proportional Hazards ◽  
Sustained Response ◽  
Phase Ii Trials ◽  
Significant Difference

3133 Background: The primary objective of EPCCT (phase I and non-randomised phase II trials) is to determine the safety and tolerability of new therapeutic agents. Response rates (RR) in these trials have typically been reported at around 10-15%. Increasingly RR and survival outcomes are now investigated in EPCCT as primary or secondary objectives. Methods: Retrospective data analysis was performed on patients (pts) enrolled onto an EPCCT between January 2018 and December 2019 at The Christie NHS Foundation Trust, UK. Data on demographics, prior systemic treatment, sites of disease, performance status, comorbidities, types of therapy, RR, progression free survival (PFS), and overall survival (OS) were collected. Statistical analyses were performed with univariable and multivariable models. Objective response rate (ORR) was defined as the proportion of pts with complete response (CR) and partial response (PR). Duration of response (DOR) was from initial response to progressive disease (PD). Disease control rate (DCR) was defined as CR+PR+ stable disease (SD). Results: A total of 247 pts were treated across 46 EPCCTs. Median age 61 years; 57% female. Sixty-six percent of pts had ≥2 lines of treatment and the majority were ECOG PS 0/1 (98%). Eighty-one percent of pts had ≥2 sites of metastatic disease, and 13 major tumour types were included. Monotherapy trials (159 pts) were predominantly targeted therapies (TT; 60%), or immunotherapies (IO; 20%). Combination therapy trials (88 pts) were TT-based (68%) or IO-based (32%). Data for RR analyses was available for 231 pts. ORR across all trials was 15% (CR 2%) and DCR was 63%. The median DOR was 8.3 months (mos) (95% CI: 7.0 – 9.7) with 28% of pts responding for >6 mos and 7% for >12 mos. ORR in pooled IO treated pts was 27%, DCR was 65% with sustained response >6 mos seen in 37% of these pts. ORR in pooled TT treated pts was 9.4%, DCR was 60% and sustained response > 6 mos seen in 25% of pts. ORR for IO v TT treated pts was significantly different, p=0.007 (pearson chi square), but no significant difference was seen for DCR. Median PFS for all patients was 5.0 mos (95% CI: 4.1 – 6.0) and OS was 10.4 mos (95% CI: 8.4 – 13.0). OS for those with a PR is not reached (HR for PR v PD, 0.006 (95% CI: 0.002 – 0.18). Pts with SD appear to have significantly better OS compared to those with PD (14.6 v 4.2 mos, HR 0.2 (95% CI: 0.1 – 0.3). Multivariable Cox proportional hazards analysis for OS was significant for male gender (HR 1.9, p=0.002), presence of liver metastasis (HR 2.0, p=0.001), low Hb (HR 0.8, p=0.03) and log (LDH) (HR 1.9, p<0.001). Conclusions: Two-thirds of pts enrolled on EPCCTs benefitted in terms of DCR with significant OS improvement in those with PR and SD. Higher ORR were seen in pts receiving IO-based treatments however DCR was similar in IO and TT pts. Gender, presence of liver metastases, Hb count and LDH level contributed significantly to survival differences.

Efficacy outcomes of nivolumab + cabozantinib versus pembrolizumab + axitinib in patients with advanced renal cell carcinoma (aRCC): Matching-adjusted indirect comparison (MAIC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4578-4578
Author(s):  
Bradley Alexander McGregor ◽  
Daniel M. Geynisman ◽  
Mauricio Burotto ◽  
Camillo Porta ◽  
Cristina Suarez Rodriguez ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Objective Response ◽  
Indirect Comparison ◽  
Progression Free Survival ◽  
Wald Test ◽  
Patient Characteristics ◽  
Cox Proportional Hazards ◽  
Published Data ◽  
Cox Proportional Hazards Models

4578 Background: Nivolumab in combination with cabozantinib (N+C) has demonstrated significantly improved progression-free survival (PFS), objective response rate (ORR), and overall survival (OS), compared with sunitinib as a first-line (1L) treatment for aRCC in the phase 3 CheckMate (CM) 9ER trial. As there are no head-to-head trials comparing N+C with pembrolizumab in combination with axitinib (P+A), this study compared the efficacy of N+C with P+A as 1L treatment in aRCC. Methods: An MAIC was conducted using individual patient data on N+C (N = 323) from the CM 9ER trial (median follow-up: 23.5 months) and published data on P+A (N = 432) from the KEYNOTE (KN)-426 trialof P+A (median follow-up: 30.6 months). Individual patients within the CM 9ER trial population were reweighted to match the key patient characteristics published in KN-426 trial, including age, gender, previous nephrectomy, International Metastatic RCC Database Consortium risk score, and sites of metastasis. After weighting, hazards ratios (HR) of PFS, duration of response (DoR), and OS comparing N+C vs. P+A were estimated using weighted Cox proportional hazards models, and ORR was compared using a weighted Wald test. All comparisons were conducted using the corresponding sunitinib arms as an anchor. Results: After weighting, patient characteristics in the CM 9ER trial were comparable to those in the KN-426 trial. In the weighted population, N+C had a median PFS of 19.3 months (95% CI: 15.2, 22.4) compared to a median PFS of 15.7 months (95% CI: 13.7, 20.6) for P+A. Using sunitinib as an anchor arm, N+C was associated with a 30% reduction in risk of progression or death compared to P+A, (HR: 0.70, 95% CI: 0.53, 0.93; P = 0.015; table). In addition, N+C was associated with numerically, although not statistically, higher improvement in ORR vs sunitinib (difference: 8.4%, 95% CI: -1.7%, 18.4%; P = 0.105) and improved DoR (HR: 0.79; 95% CI: 0.47, 1.31; P = 0.359). Similar OS outcomes were observed for N+C and P+A (HR: 0.99; 95% CI: 0.67, 1.44; P = 0.940). Conclusions: After adjusting for cross-trial differences, N+C had a more favorable efficacy profile compared to P+A, including statistically significant PFS benefits, numerically improved ORR and DoR, and similar OS.[Table: see text]

Association between rigors and overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients treated with high-dose interleukin-2 (HD IL-2).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 487-487
Author(s):  
Julia Anne Batten ◽  
Wolfram E. Samlowski ◽  
Kinjal Parikh ◽  
Arun Sendilnathan ◽  
Hilda Crispin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Proportional Hazards ◽  
Objective Response ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
High Dose ◽  
University Of Utah ◽  
Cox Proportional Hazards Models ◽  
Grade 3

487 Background: HD IL-2 is associated with an objective response rate of 16-20% with durability of response in select mRCC patients. HD IL-2 is also associated with significant toxicity including vascular leak syndrome and inflammatory side effects. Few predictive markers can identify patients likely to respond to HD IL-2. Methods: Patients treated with HD IL-2 at the University of Utah Huntsman Cancer Institute from 2000 to 2012 with clear cell mRCC were evaluated. Grade of toxicities during HD IL-2 treatment were collected based on provider documentation in the electronic health record. Rates of adverse events (AEs) and overall survival stratified grade 3 AEs were evaluated by Kaplan-Meier survival estimates and Cox proportional hazards models. All AEs were graded per common terminology criteria version 4. Grade 3 rigors were defined as severe rigors requiring opioids. Results: A total of 85 patients were included with a median age of 56 years (range 32-76 years) and 79% (n = 67) were male. Patients belonged to the following MSKCC risk categories: 11 (13%) good, 70 (82%) intermediate, and 4 (5%) poor risk. The mean total dose received was 1097 MIU (range: 160 – 3048 MIU). The prevalence of grade 3 AEs is presented in the table. Median survival of patients with ≥grade 3 rigors after HD IL-2 administration was 1501 days vs 533 days for those without (p = 0.0005, HR 2.54). Presence of rigors was also associated with a significant improvement in progression free survival, time to next treatment and response rates. No other AEs predicted response to HD IL-2. Conclusions: Presence of grade 3 rigors predicts improved survival during HD IL-2 therapy. Notably, grade 3 fever was rarely observed because of our institutional protocol of routinely using scheduled antipyretics to diminish fevers. [Table: see text]

Amphiregulin (AREG) expression and response to first-line panitumumab (pmab) plus FOLFIRI in metastatic colorectal cancer (mCRC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 731-731
Author(s):  
Claus-Henning Kohne ◽  
Ralf Hofheinz ◽  
Laurent Mineur ◽  
Henry Letocha ◽  
Richard Greil ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Quantitative Polymerase Chain Reaction ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Treatment Decision ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
First Line ◽  
Treatment Benefit ◽  
Formalin Fixed Paraffin Embedded

731 Background: Biomarker analyses have shown that patients (pts) with RAS wild-type (WT) mCRC can achieve overall survival (OS) benefits with first-line pmab plus chemotherapy. Other biomarkers may exist that could optimize pt selection. Epidermal growth factor receptor ligand (eg AREG) levels have been correlated with OS during anti-EGFR therapy. Here we investigate the relationship between AREG expression and treatment outcome in a single-arm first-line mCRC study of pmab + FOLFIRI. Methods: Qualified reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays were used to measure AREG RNA expression in archival formalin-fixed, paraffin embedded tumor samples from mCRC pts in two pmab trials (STEPP and 314). The STEPP analysis was used to establish a cut-off point in AREG expression that identified the best responders. This cut-off was applied prospectively to samples previously analyzed for KRAS in the 314 trial. Using the KRASMT subgroup as a non-responding comparator, Cox proportional hazards (PH) models were used to evaluate AREG expression levels as a continuous covariate. Decision curves were used to estimate the progression-free survival (PFS) hazard ratio (HR) with increasing levels of baseline AREG expression. Results: In the 314 trial 100 pts had evaluable AREG levels. Among 50 KRAS WT pts, high AREG expression was associated with objective response (OR) (Table). The high AREG group had better PFS HRs (KRAS WT/KRAS MT: 0.30 [95% CI, 0.12–0.75]) compared with the low AREG group (PFS HR 0.49 [95% CI 0.21–1.1]). There was a significant biomarker-by-AREG expression interaction in the Cox PH model (p=0.03). Conclusions: Treatment decision curves based on the PH model suggest that most KRAS WT patients express AREG at levels where treatment benefit is predicted. Future analysis of samples from a RASWT population may provide further insights. Clinical trial information: NCT00508404. [Table: see text]

Effect of baseline carbohydrate antigen 19-9 (CA19-9) level on overall survival (OS) in NAPOLI-1 trial: A phase III study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin (5-FU/LV), versus 5-FU/LV in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 425-425 ◽  
Author(s):  
Li-Tzong Chen ◽  
Jens T Siveke ◽  
Andrea Wang-Gillam ◽  
Richard Hubner ◽  
Shubham Pant ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Effect ◽  
Proportional Hazards ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Response To Therapy ◽  
Phase Iii ◽  
Free Survival ◽  
Previously Treated

425 Background: CA19-9 has been shown to correlate with response to therapy and OS in patients with mPAC. NAPOLI-1, a randomized phase 3 study evaluated nal-IRI, a nanoliposomal formulation of irinotecan, with or without 5-FU/LV vs 5-FU/LV in patients with mPAC previously treated with gemcitabine-based therapy. Nal-IRI+5-FU/LV significantly improved OS (primary endpoint) vs 5-FU/LV (6.1 mo vs 4.2 mo; unstratified hazard ratio [HR] = 0.67; P = 0.012). CA19-9 response (≥50% decline from baseline) was superior with nal-IRI+5FU/LV compared with 5-FU/LV (29% vs 9%; P=0.0006). Nal-IRI alone did not show a statistical improvement in survival. Methods: Patients with a recorded baseline CA19-9 measurement were divided into quartiles to evaluate the treatment effect pattern of CA19-9 from nal-IRI+5-FU/LV and 5-FU/LV arms. Quartile ranges were based on 404 available CA19-9 values from randomized patients (N=417). Unstratified Cox proportional hazards regression was used to estimate HRs and corresponding 95% CIs. Effect of baseline CA19-9 on time to response, progression-free survival, and response will be presented. Results: Of patients randomized to receive nal-IRI+5-FU/LV (n = 117) or 5-FU/LV enrolled contemporaneously (n = 119), 218 received study drug and had a baseline CA19-9 measurement. Results show a greater treatment effect on OS with higher CA19-9 level relative to 5-FU/LV. Conclusions: In patients with mPAC previously treated with gemcitabine-based therapy, nal-IRI+5-FU/LV significantly improved OS supported by progression free survival and objective response rate. The CA19-9 serum level can provide important information with regards to overall survival. Clinical trial information: NCT01494506. [Table: see text]

scholarly journals Reductions in AFP and PIVKA-II can predict the efficiency of anti-PD-1 immunotherapy in HCC patients

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuqi Sun ◽  
Jie Mei ◽  
Wenping Lin ◽  
Ziliang Yang ◽  
Wei Peng ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Objective Response ◽  
Binary Logistic Regression ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Related Factors ◽  
Hazards Model ◽  
Before And After

Abstract Background Few biomarkers can predict the efficiency of PD-1 blockade in patients with hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic role of AFP and PIVKA-II in HCC patients receiving anti-PD-1 immunotherapy. Methods A total of 235 HCC patients treated with PD-1 blockade were enrolled. Serum AFP and PIVKA-II levels were collected before and after treatments. The patients were divided into groups based on the reduction in AFP and PIVKA-II: AFP reduction ≤50% vs AFP reduction > 50% and PIVKA-II reduction ≤50% vs PIVKA-II reduction > 50%. The primary endpoints included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Binary logistic regression analyses were used to explore the related factors of ORR. A Cox proportional hazards model was employed to identify the potential prognostic factors of PFS and OS. Results Among all the patients, 34.9% (82/235) achieved a complete or partial response. There was a positive correlation between AFP reduction > 50% or PIVKA-II reduction> 50% and the ORR of PD-1 blockade (P < 0.001 and = 0.003). PFS was significantly improved in patients with AFP reduction > 50% and PIVKA-II reduction > 50% (p < 0.001 and = 0.021). In addition, AFP reduction > 50% and PIVKA-II reduction> 50% were positively correlated with longer OS (p = 0.003 and 0.006). Conclusion Early reductions in AFP and PIVKA-II can be predictors of the efficacy of PD-1 blockade in HCC patients.

The association of tissue tumor mutational burden (tTMB) using the Foundation Medicine genomic platform with efficacy of pembrolizumab versus paclitaxel in patients (pts) with gastric cancer (GC) from KEYNOTE-061.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4537-4537 ◽  
Author(s):  
Kohei Shitara ◽  
Mustafa Özgüroğlu ◽  
Yung-Jue Bang ◽  
Maria Di Bartolomeo ◽  
Mario Mandalà ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Positive Association ◽  
Progression Free Survival ◽  
Wald Test ◽  
Cox Proportional Hazards ◽  
Open Label ◽  
Ecog Performance Status

4537 Background: KEYNOTE-061 (NCT02370498) was a randomized, open-label, phase 3 study of pembrolizumab vs paclitaxel in pts with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma with tumor progression after first-line therapy (N = 592). In this analysis, we evaluated tTMB using FoundationOne CDx (F1CDx; Foundation Medicine) in pts with gastric or GEJ cancer in KEYNOTE-061. Methods: In pts with evaluable F1CDx tTMB data (n = 204), we analyzed the association of tTMB with confirmed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) within each treatment arm using one-sided (pembrolizumab) and two-sided (paclitaxel) Wald test nominal P for logistic regression (ORR) and Cox proportional hazards regression (PFS; OS) adjusted for ECOG performance status; significance was prespecified at 0.05. The clinical utility of tTMB was assessed using the prespecified cutoff of 10 mut/Mb for F1CDx. Clinical data cutoff: Oct 26, 2017. Results: tTMB was positively associated with ORR ( P < 0.001; AUROC, 0.68), PFS ( P < 0.001), and OS ( P = 0.003) with pembrolizumab but not paclitaxel (ORR, P = 0.047; AUROC, 0.30; PFS, P = 0.605; OS, P = 0.084). Pt outcomes by tTMB cutoff are reported in the Table; prevalence of TMB ≥10 mut/Mb was 17%. In pts with microsatellite stable disease-only, HRs (95% CI) by treatment arm for OS by F1CDx cutoff were 0.40 (0.14-1.17) for tTMB ≥10 mut/Mb (n = 21) vs 0.97 (0.70-1.34) for tTMB <10 mut/Mb (n = 168). Conclusions: In this exploratory analysis from KEYNOTE-061, tTMB as determined by F1CDx demonstrated a positive association with clinical outcomes with pembrolizumab, but not paclitaxel, in pts with GC; these findings are consistent with those reported with whole exome sequencing. Pembrolizumab demonstrated an OS benefit vs paclitaxel in the subgroup with tTMB ≥10 mut/Mb, which remained when pts with microsatellite instability-high disease were excluded. Clinical trial information: NCT02370498 . [Table: see text]

Plasma VEGF-a, angiopoietin-2 (ANG2) and soluble(s)TIE2 in patients (pts) with HER2-negative locally recurrent or metastatic breast cancer (LR/MBC) treated with first-line bevacizumab (A) and paclitaxel (T) without or with capecitabine (X).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1072-1072
Author(s):  
Siu W. Lam ◽  
Steffen M. de Groot ◽  
Aafke H. Honkoop ◽  
Nienke M. Nota ◽  
A. Jager ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Response Duration ◽  
Continuous Variable ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
First Line

1072 Background: In the randomized phase II ATX trial, pts with HER2-negative LR/MBC were treated with first-line AT or ATX. We determined the prognostic value for outcome of VEGF-A, ANG2 and sTIE2 measured at baseline on cycle 1 day 1 (C1D1) and after cycle 1 (C2D1). Methods: 312 pts were randomized in 1:1 ratio to AT (T 90 mg/m2 on d1, 8, 15 and A 10 mg/kg on d1, 15 q4w x 6 cycles, followed by A 15 mg/kg on d1 q3w for next cycles) or ATX (T 90 mg/m2 on d1, 8, A 15 mg/kg on d1 and X 825 mg/m2bid on d1–14 q3w x 8 cycles, followed by the same dose of A and X q3w for next cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), response duration (RD), overall survival (OS) and safety. Plasma proteins on C1D1 (N = 173) and on C2D1 (N = 142) were measured by ELISA. The association of protein levels (continuous variable) with PFS and OS was evaluated by Cox proportional hazards model and Martingale residual plot. Results: At a median follow-up of 39 months (mo), there were 292 PFS events and 242 deaths. ATX significantly improved PFS as compared to AT (median 11 vs. 8.4 mo, stratified HR = 0.52; 95% CI, 0.41 – 0.67; P < .001). The confirmed ORR in measurable disease (N = 268) was 67% in ATX vs. 50% in AT. Median RD was 6.4 mo (95% CI, 6.1 – 8.3) in ATX v 5.4 mo (95% CI, 5.1 – 6.0) in AT. Median OS was 24.1 mo in ATX vs. 23.1 mo in AT (P= .44). The aselected ‘biomarker’ cohort (N = 173) and overall trial cohort had similar baseline characteristics. ANG2 on C1D1 moderately correlated with sTIE2 on C1D1 (Pearson’s r = .44, P < .001). High ANG2 on C1D1 was significantly associated with poor OS (HR = 1.6; 95% CI, 1.1 – 2.3; P = .01), but not with poor PFS (HR = 1.3; 95% CI, 1.0 – 1.3; P = .07). ANG2 on C2D1 was not significantly associated with OS (HR = 1.55; 95% CI, 0.99 – 2.4; P = .057) or with PFS (P= .6). sTIE2 and VEGF-A were not associated with outcome. All pts had very low levels of free VEGF-A on C2D1 (median 8 pg/ml). Conclusions: In HER2-negative LR/MBC, ATX is more effective (PFS, ORR and RD) than AT. A very high plasma level of ANG2 at baseline indicates a high risk for poor survival. Clinical trial information: NTR1348.

Sunitinib in patients with pancreatic neuroendocrine tumors (panNETs): Exploratory pharmacogenomic analyses.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 255-255
Author(s):  
Nicola Fazio ◽  
Jean-Francois Martini ◽  
Adina-Emilia Croitoru ◽  
Michael Schenker ◽  
Sherry Li ◽  
...  
Keyword(s):  
Protein Transport ◽  
Proportional Hazards ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Nucleotide Polymorphisms ◽  
Exact Test ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Treatment Naïve

255 Background: In a phase IV trial (NCT01525550), median progression-free survival (PFS) was 13.2 mo in sunitinib-treated patients (pts) with well-differentiated panNETs. Objective response rate (ORR) was 24.5% and median overall survival (OS) was 37.8 mo. Exploratory analyses evaluated potential associations between single nucleotide polymorphisms (SNP) in genes involved in angiogenesis, protein transport or inflammatory response and clinical outcomes. Methods: Blood samples were genotyped using TaqMan assays for 12 SNPs previously associated with panNET risk, prognosis or drug effect. Associations between SNP and PFS or OS were assessed by comparing genotypes within treatment-naïve (TN), previously treated (PT) and combined groups, and within a genotype between treatment groups, using Kaplan-Meier analysis and Cox proportional hazards models. Fisher’s exact test was used for association between ORR and genotype. PFS and ORR were investigator-assessed. P values displayed are unadjusted and Bonferroni method was used for multiplicity adjustment. Results: 56 pts were genotyped: 25 TN and 31 PT. There were no significant associations between genotype and PFS or OS but there was a trend toward shorter PFS in pts with VEGFR1 rs9554320 C/A versus C/C (hazard ratio [HR] 1.78; 95% confidence interval [CI] 0.83–3.82; p = 0.117) and VEGFR1 rs9582036 A/C versus A/A (HR 1.88; 95% CI 0.9–3.93; p = 0.102). The genotypes G/G of VEGFA rs2010963 (p = 0.041) , G/G of VEGFA rs833068 (p = 0.041) and A/C of VEGFR1 rs9582036 (p = 0.046) showed a trend toward a higher ORR in the PT versus TN group. Genotype T/T of VEGFR2 rs7692791 (p = 0.103) showed a trend toward to a lower ORR in the TN versus PT group. Higher ORR was associated with IL1B rs16944 G/A versus G/G (46.4% vs 4.5%; p = 0.001) in the combined group. Conclusions: Potential associations between ORR and VEGFA rs2010963 and rs833068, VEGFR1 rs9582036 and VEGFR2 rs7692791 were observed. IL1B rs16944 was significantly associated with ORR, consistent with the role of IL1B in panNET etiology and development. Most correlations were not significant after adjustment for multiplicity. Clinical trial information: NCT01525550.

Impact of lenvatinib (LEN) dose-intensity and starting dose on survival among patients with advanced hepatocellular carcinoma (HCC): Results from a Canadian multicenter database (HCC CHORD).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16142-e16142
Author(s):  
Carla Pires Amaro ◽  
Michael J Allen ◽  
Jennifer J. Knox ◽  
Erica S. Tsang ◽  
Howard John Lim ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Objective Response ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Advanced Hepatocellular Carcinoma ◽  
First Line ◽  
Cox Proportional Hazards Models ◽  
Starting Dose ◽  
Localized Treatment

e16142 Background: The REFLECT trial established LEN as a first-line treatment option for HCC. However, decreased LEN exposure is common due to adverse events leading to dose reductions and treatment discontinuations. The aim of this study was to evaluate whether starting dose or dose-intensity of LEN affects survival. To our knowledge, this is the first study to examine dosing of LEN and survival in HCC patients treated outside of Asia. Methods: From July 2018 to December 2019, HCC patients treated with first-line LEN from 10 different Canadian cancer centers were included. Overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and objective response rate (ORR) were retrospectively analyzed and compared across different mean dose-intensities (> 66.7% vs <=66.7%) and starting dose groups (Full vs reduced). Survival outcomes were assessed with Kaplan-Meier curves and Cox proportional hazards models. DCR and ORR were determined radiographically according to the treating physician´s assessment in clinical notes and not RECIST 1.1 or mRECIST. Results: A total of 173 patients were included. Median age was 67 years, 77% were men and 23% East Asian. The most frequent causes of liver disease were hepatitis C (38%) and B (20%). 56% of patients received localized treatment prior to LEN. Of those, 24% had TACE, 6% TARE and 8% had liver transplant. Before starting LEN 31% of patients were ECOG 0 and 57% were ECOG 1. Most patients were Child-Pugh A (81%) and BCLC stage C (73%). Main portal vein invasion was present in 15% of the patients. Median follow-up was 4.5 months. LEN was started at full dose in 54% of patients and 60% had a mean dose intensity greater than 66.7%. ORR, PFS and OS results and their comparison between the different starting dose and dose-intensities are shown in the table. In a multivariate model that adjusted for age, gender, stage, ECOG, Child-Pugh, BCLC, cirrhosis, liver etiology disease (hepatitis B, C and non-viral), presence of tumor thrombus, prior transplant and localized treatment, dose intensity (>66.7 vs <=66.7% [HR 0.70, 95% CI 0.42-1.18; p=0.18]) was not a predictor of survival. Conclusions: In HCC patients starting LEN at a reduced dose does not appear to compromise survival. LEN dose-intensity of > 66.7% was associated with improved survival, but not after controlling for potential confounders.[Table: see text]

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