Outcomes of patients (pts) with metastatic renal cell carcinoma (mRCC) treated with pazopanib after progression on other targeted therapies (TT): A single-institution experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4615-4615
Author(s):  
Marc Ryan Matrana ◽  
Aditya V. Shetty ◽  
Bradley J. Atkinson ◽  
Lianchun Xiao ◽  
Paul G. Corn ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Kinase Inhibitor ◽  
Multivariable Analysis ◽  
Safety Data ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Treatment Naïve ◽  
Metastatic Sites

4615 Background: Pazopanib is an approved multi-tyrosine kinase inhibitor that prolongs progression-free survival (PFS) compared to placebo in treatment-naive and cytokine-refractory mRCC. Outcomes and safety data on its use after TT are limited. Methods: We retrospectively reviewed pts with mRCC who received salvage pazopanib between 11/09-11/11. Kaplan-Meier method was used to estimate survival outcomes. PFS was calculated from start of pazopanib until progressive disease (PD) or death. Univariable and multivariable Cox proportional hazards models were fitted to evaluate associations of PFS with covariables. Results: 114 consecutive pts met inclusion criteria (median age 62.6 years, 66% males, 83% clear cell). All pts had PD after other TT (median # of prior TT 2, range 1-5; median time on prior TT 23.3 mos). 79% of pts had PD on sunitinib, 39% on sorafenib, 19% on temsirolimus, 59% on everolimus, and 23% on bevacizumab. 25% received prior chemotherapy and 16% received prior cytokines in addition to TT. 87% had prior nephrectomy. 11% had favorable-risk, 68% intermediate-risk, and 21% poor-risk per MSKCC criteria. 85 events (PD or death) occurred. Median OS was 17 mos (95% CI: 10.3-NA). Median PFS was 6.4 mos (95% CI: 4.5-9.5). By multivariable analysis, PFS was associated with male gender (HR=0.433, 95%CI: 0.269-0.696; p=0.0006), # of metastatic sites (HR=1.252; 95%CI: 1.04-1.503; p=0.016), hypertension exacerbation (HR=0.378; CI: 0.175-0.813; p=0.0128) and PS 2+ vs.0-1 (HR=2.067; CI: 1.243-3.437; p=0.0052). 58% discontinued pazopanib due to PD, 12% died of PD on treatment, and 11% discontinued pazopanib due to adverse events (AEs), mostly GI complaints or fatigue. There were no treatment related deaths. Common AEs included: fatigue (44%), diarrhea (29%), nausea/vomiting (15%), anorexia (14%), hypertension exacerbation (11%), hypothyroidism (11%), hand-foot skin reaction (9%), and increase LFTs (4%). 86% of AEs were grade 1/2. Conclusions: In this retrospective study, pazopanib demonstrated efficacy in mRCC following PD with other TT. AEs were mild/moderate and manageable.

Outcomes of patients (pts) with metastatic renal cell carcinoma (mRCC) treated with pazopanib after progression on other targeted therapies (TT): Updated results.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 367-367
Author(s):  
Marc Ryan Matrana ◽  
Cihan Duran ◽  
Aditya Shetty ◽  
Lianchun Xiao ◽  
Bradley J. Atkinson ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Kinase Inhibitor ◽  
Clear Cell ◽  
Progression Free Survival ◽  
Median Number ◽  
Cox Proportional Hazards ◽  
Clinical Activity ◽  
Pancreatic Metastases ◽  
Cox Proportional Hazards Models ◽  
Treatment Naïve

367 Background: Pazopanib is an multi-tyrosine kinase inhibitor shown to prolong progression-free survival (PFS) compared to placebo in treatment-naive and cytokine-refractory mRCC. Outcomes and safety on its use after TT are limited. Methods: We retrospectively reviewed records of consecutive pts with mRCC who were treated with pazopanib between November 2009-November 2011 after having progressive disease (PD) with other TT. Radiographic response was assessed by a blinded radiologist using RECIST v1.1 criteria. PFS and overall survival (OS) were estimated by the Kaplan-Meier method. Hazard ratios (HR) were estimated by fitting univariable and multivariable Cox proportional hazards models to evaluate the association of PFS with patient co-variates. Results: 112 pts (median age 63 years, 67% male, 83% clear cell) met inclusion criteria. Median number of previous TT was 2 (range 1-5). 85 events (PD or death) occurred. 14 pts (12.5%) had a partial response. Median PFS was 5.7 months (95% CI: 4.3-8.9 months). PFS was significantly associated with male gender (HR=0.55; 95% CI: 0.34-0.87; p=0.011), clear-cell histology (HR=0.42; 95% CI: 0.24-0.74; p=0.0031), number of metastatic sites (HR= 1.26; 95% CI: 1.05-1.52; p=0.0123), pancreatic metastases (HR=0.40; 95% CI: 0.18-0.85;p=0.0185), Karnofsky PS< 80 (HR=2.07; 95% CI: 1.22-3.48; p=0.0062), and elevated LDH (HR=1.63; 95% CI: 1.03-2.573; p=0.035). Median OS was 16.9 months (95% CI: 10.3–21.9). 26% of pts were still receiving pazopanib at the time of analysis. 51% discontinued pazopanib due to PD and 12% died of PD on treatment. 11% discontinued pazopanib due to adverse events (AEs). There were no treatment related deaths. Common AEs included fatigue (43%), increase LFTs (34%), diarrhea (28%), nausea/vomiting (14%), anorexia (14%), hypertension exacerbation (12%), and hypothyroidism (11%). 89% of AEs were grade 1/2. Conclusions: Pazopanib demonstrated meaningful clinical activity in heavily pretreated pts with mRCC following PD with other TT. AEs were mild/moderate and manageable.

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.

scholarly journals Clinical outcomes in patients with metastatic renal cell carcinoma receiving everolimus or temsirolimus after sunitinib.

2014 ◽  
Vol 8 (3-4) ◽  
pp. 121 ◽  
Author(s):  
Roberto Iacovelli ◽  
Giacomo Cartenì ◽  
Michele Milella ◽  
Rossana Berardi ◽  
Giuseppe Di Lorenzo ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Kinase Inhibitor ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Clinical Activity ◽  
Second Line ◽  
Cox Proportional Hazards Models ◽  
Line Setting

Introduction: There are little data on the clinical activity of temsirolimus (TM) and everolimus (EV) when used as second-line therapy after sunitinib (SU) in patients with metastatic renal cellcarcinoma (mRCC).Methods: Patients with mRCC treated with EV or TM after SU were included in this retrospective analysis. Progression-free survival (PFS), time to sequence failure (TTSF) from the start of SU to disease progression with EV/TM and overall survival (OS) were estimated using Kaplan-Meier method and compared across groups using the log-rank test. Cox proportional hazards models were applied to investigate predictors of TTSF and OS.Results: In total, 89 patients (median age 60.0 years) were included. At baseline 43% were classified as MSKCC good-risk, 43% as intermediate-risk and 14% as poor-risk. Median OS was 36.3 months and median TTSF was 17.2 months. Sixty-five patients received SU-EV and 24 patients SU-TM. Median PFS after the second-line treatment was 4.3 months in the EV group and 3.5 months in the TM group (p = 0.63). Median TTSF was 17.0 and 18.9 months (p = 0.32) and the OS was 35.8 and 38.3 months (p = 0.73) with SU-EV and SU-TM, respectively. The prognostic role of initial MSKCC was confirmed by multivariable analysis (hazard ratio 1.76, 95% confidence interval 1.08-2.85. p = 0.023).Conclusions: This study did not show significant differences in terms of disease control and OS between EV and TM in the second-line setting. EV remains the preferred mTOR inhibitor for the treatment of mRCC patients resistant to prior tyrosine kinase inhibitor treatment.

scholarly journals Does Very Poor Performance Status Systematically Preclude Single Agent Anti-PD-1 Immunotherapy? A Multicenter Study of 35 Consecutive Patients

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1040
Author(s):  
Valérie Gounant ◽  
Michael Duruisseaux ◽  
Ghassen Soussi ◽  
Sylvie Van Hulst ◽  
Olivier Bylicki ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Cox Proportional Hazards ◽  
Poor Performance Status ◽  
Low Grade ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models

Anti-PD-1 antibodies prolong survival of performance status (PS) 0–1 advanced non-small-cell lung cancer (aNSCLC) patients. Their efficacy in PS 3–4 patients is unknown. Conse- cutive PS 3–4 aNSCLC patients receiving compassionate nivolumab were accrued by 12 French thoracic oncology departments, over 24 months. Overall survival (OS) was calculated using the Kaplan-Meier method. Prognostic variables were assessed using Cox proportional hazards models. Overall, 35 PS 3–4 aNSCLC patients (median age 65 years) received a median of 4 nivolumab infusions (interquartile range [IQR], 1–7) as first- (n = 6) or second-line (n = 29) therapy. At a median of 52-month follow-up (95%CI, 41–63), 32 (91%) patients had died. Median progression-free survival was 2.1 months (95%CI, 1.1–3.2). Median OS was 4.4 months (95%CI, 0.5–8.2). Overall, 20% of patients were alive at 1 year, and 14% at 2 years. Treatment-related adverse events occurred in 8/35 patients (23%), mostly of low-grade. After adjustment, brain metastases (HR = 5.2; 95%CI, 9–14.3, p = 0.001) and <20 pack-years (HR = 4.8; 95%CI, 1.7–13.8, p = 0.003) predicted worse survival. PS improvement from 3–4 to 0–1 (n = 9) led to a median 43-month (95%CI, 0–102) OS. Certain patients with very poor general condition could derive long-term benefit from nivolumab salvage therapy.

Efficacy and safety of zanubrutinib versus rituximab-based chemoimmunotherapy in Waldenström macroglobulinemia (WM): Matching-adjusted indirect comparisons.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7559-7559
Author(s):  
Jorge J. Castillo ◽  
Keri Yang ◽  
Rongzhe Liu ◽  
Yu Wang ◽  
Aileen Cohen ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Weighted Average ◽  
Hemoglobin Concentration ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Cox Proportional Hazards ◽  
International Prognostic Scoring System ◽  
Cox Proportional Hazards Models ◽  
Treatment Naïve ◽  
Indirect Comparisons

7559 Background: Given a lack of WM randomized trials directly comparing zanubrutinib with chemoimmunotherapy, this study aimed to indirectly compare zanubrutinib with bendamustine-rituximab (BR) and with dexamethasone-rituximab-cyclophosphamide (DRC) separately through matching-adjusted indirect comparisons (MAIC). Methods: MAIC were conducted to re-weight the individual data of 102 WM patients (83 relapsed/refractory [R/R] and 19 treatment-naïve [TN]) treated with zanubrutinib in the ASPEN trial (NCT03053440) so that the weighted average baseline characteristics of patients treated with zanubrutinib matched those of 71 R/R patients treated with BR, and 72 TN patients treated with DRC separately. Matching variables for MAIC with BR included age, prior lines of therapy, IgM concentration, International Prognostic Scoring System for WM score, and extramedullary disease (EMD); and for MAIC with DRC included age, platelet count, hemoglobin concentration, and EMD. Kaplan-Meier curves of progression-free survival (PFS) and overall survival (OS) of comparators were digitized to re-create patient-level data. Comparisons of survival and adverse event incidence between treatments were conducted using Cox proportional hazards models and modified Poisson models. Results: Compared to DRC, zanubrutinib was associated with longer PFS (hazard ratio [HR]: 0.39 [95% confidence interval 0.18-0.82] and 0.35 [0.14-0.86] pre- and post-matching, respectively) and longer OS (HR: 0.56 [0.20-1.53] and 0.47 [0.14-1.62] pre- and post-matching, respectively), and insignificantly higher incidences of neutropenia (risk ratio [RR]: 1.63 [0.71-3.77] and 1.47 [0.58-3.74] pre- and post-matching, respectively). Compared to BR, zanubrutinib was associated with longer PFS (HR: 0.32 [0.15-0.69] and 0.37 [0.15-0.91] pre- and post-matching, respectively), longer OS (HR: 0.31 [0.12, 0.80] and 0.29 [0.10-0.85] pre- and post-matching, respectively), lower incidences of neutropenia (RR: 0.45 [0.26-0.78] and 0.50 [0.27-0.91] pre- and post-matching, respectively) and lower incidences of pneumonia (RR: 0.18 [0.02-1.55] and 0.26 [0.03-2.28] pre- and post-matching, respectively). Conclusions: Zanubrutinib demonstrated longer PFS than DRC, and longer PFS and OS than BR in WM, before and after matching adjustment based on patient characteristics. [Table: see text]

Biomarker analysis from a phase III trial (GOLD) of dovitinib (Dov) versus sorafenib (Sor) in patients with metastatic renal cell carcinoma after one prior VEGF pathway–targeted therapy and one prior mTOR inhibitor therapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 473-473 ◽  
Author(s):  
Bernard J. Escudier ◽  
Camillo Porta ◽  
Matthew Squires ◽  
Cezary Szczylik ◽  
Christian K. Kollmannsberger ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Plasma Samples ◽  
Plasma Biomarkers ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Biomarker Analysis ◽  
Line Setting

473 Background: In the GOLD trial, Dov did not improve progression-free survival (PFS) or overall survival (OS) over Sor. An exploratory objective of the study was to investigate plasma and tumor biomarkers to predict outcome. Methods: Plasma samples were obtained longitudinally throughout the study, and biomarkers were assessed by immunoassay. Primary archival tumor samples were assessed by immunohistochemistry. Log-rank tests, stratified by baseline MSKCC risk group, for difference in Kaplan-Meier curves between biomarker category (low/high based on </≥ median baseline values) within treatment arm were performed. Hazard ratios (HRs) were estimated from Cox proportional hazards models. Results: Plasma samples were available from 561 patients (Dov, n = 281; Sor, n = 280), and tumor samples were available from 341 patients (Dov, n = 181; Sor, n = 160). Baseline plasma biomarker levels were not predictive of Dov or Sor PFS or OS. However, strong prognostic effects, particularly for OS, were observed. High baseline cKIT and low baseline FGF2, HGF, PlGF, sVEGFR1, VEGFA, and VEGFD were associated with better OS for both Dov and Sor (Table). Changes from baseline in a number of plasma biomarkers were observed following treatment with Dov and Sor, consistent with VEGFR/FGFR inhibitory effects. Prognostic effects were also observed for low FGFR2 (PFS) and low FGF2 (OS) expression in archival tumors. Conclusions: Baseline plasma biomarkers are prognostic but not predictive in the third-line setting. Clinical trial information: NCT01223027. [Table: see text]

Association between post-treatment (tx) alpha-fetoprotein (AFP) reduction and outcomes in real-world (rw) U.S. patients (pts) with advanced HCC (aHCC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 341-341
Author(s):  
Xiaoliang Wang ◽  
Kelly Magee ◽  
Anala Gossai ◽  
Christina M. Parrinello ◽  
Rebecca A. Miksad ◽  
...  
Keyword(s):  
Risk Factor ◽  
Alcohol Use ◽  
Proportional Hazards ◽  
No Reduction ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Baseline Serum ◽  
Cox Proportional Hazards Models ◽  
The Impact

341 Background: A decrease in post-tx AFP may be associated with improved outcomes in clinical trials. However, the impact of AFP reduction after initiation of a first-line (1L) tyrosine kinase inhibitor (TKI) therapy on outcomes is unclear among pts with aHCC treated in routine clinical practice. Methods: This analysis utilized data from the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database and included pts with aHCC with ≥2 visits between 1/1/2011-7/31/2019 who received 1L TKI. Pts with a baseline serum AFP value (closest to 1L initiation within -30 to +7 days) and a post-tx AFP value (closest to 8 weeks after 1L initiation within ±2 weeks) were included. Post-tx AFP reduction was defined as a ≥20% decrease from baseline AFP, and no reduction as a <20% decrease or any increase. Rw overall survival (rwOS) was defined as time from post-tx AFP measurement to death (censored at last EHR activity). Rw progression-free survival (rwPFS) was based on clinician documentation and defined as the first progression event or death after post-tx AFP measurement (censored at last clinic note date). Adjusted hazard ratios (aHR) for reduction vs no reduction (reference) were estimated using multivariable Cox proportional hazards models adjusted for potential confounders and baseline AFP. Effect modification was assessed by conducting tests for interactions with analyses stratified by HCC risk factors. Results: 441 pts were included in the study. 8% had documented history (hx) of hepatitis B (HBV), 52% hepatitis C (HCV), 47% obesity/diabetes (DM), 42% heavy alcohol use, and 11% no documented risk factor. Median baseline AFP was 210 ng/mL (IQR 237 - 2981) and 150 ng/mL (IQR 17 - 1311) among pts with reduction (N = 150) and no reduction (N = 291). There was a 35% decrease in hazard of death for pts with reduction vs no reduction (median rwOS 10.3 vs 6.7 months; Table). Similarly, a 35% decrease in hazard of rw progression or death was observed for pts with reduction vs no reduction (aHR=0.65; 95% CI: 0.52-0.81; median rwPFS 4.4 vs 2.4 months). Reduction (vs no) was associated with better rwOS among pts with hx of HCV, obesity/DM or alcohol use vs without the respective risk factor, however, no statistically significant interactions were observed (Table). Conclusions: Results show post-tx AFP reduction may be prognostic for rwPFS and rwOS in pts with aHCC treated with 1L TKI. Further research may clarify if prognostic value differs by HCC risk factor profile. [Table: see text]

Circulating tumor DNA fraction (ctDNA%) to independently predict for clinical outcomes in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5049-5049
Author(s):  
Corinne Maurice-Dror ◽  
Nicolette Fonseca ◽  
Cameron Herberts ◽  
William Fan ◽  
Alexander W. Wyatt ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Cox Proportional Hazards ◽  
Castration Resistant Prostate Cancer ◽  
Prognostic Information ◽  
Kaplan Meier ◽  
Treatment Naïve ◽  
Ecog Ps

5049 Background: CtDNA% (the tumour-derived proportion of cell-free DNA (cfDNA)) is abundant in >60% of mCRPC pts and associates with adverse clinical prognostic factors. However, prognostic associations have not been comprehensively tested across clinical contexts. We evaluated the utility of ctDNA% as an independent prognostic biomarker in patients with mCRPC prior to first-line (1L) therapy. Methods: 410 treatment-naïve mCRPC pts had blood samples drawn prior to 1L therapy and followed prospectively for outcomes. Plasma cfDNA was subjected to deep targeted sequencing and ctDNA% was calculated using validated methods ( Annala, Cancer Discov, 2018 ). Overall survival (OS), PSA progression free survival (PSA PFS) and PSA declines ≥50% from baseline (PSA50 response rate (RR)) were stratified by ctDNA% and compared using Kaplan-Meier and Cox proportional hazards analysis. Results: Median age was 73 yrs. (range 45-98), the majority of pts had ECOG PS 0-1 (78%) and 9.5% had liver metastases at baseline. The most common 1L therapy employed was androgen receptor pathway inhibitors (90%). Median follow-up was 21 mo. (range 1-75) and median ctDNA% was 4.9% (range: 0-89%). Stratifying patients into high ctDNA (>30%) and Low ctDNA (≤2%) groups showed stronger association with OS and PSA PFS than grouping by median (Table). In a univariate comparison to pts with low ctDNA (≤2%), pts with high ctDNA% (>30%) had significantly shorter median PSA PFS, median OS and a lower PSA50 RR (Table). In a multivariable adjustment for clinical prognostic factors and cfDNA concentration, high ctDNA% remained strongly associated with OS (HR= 3.3, 95%CI: 2.1-5.3, p<0.001) and PSA PFS (HR: 3.7, 95%CI: 2.4-5.9, p<0.001). Although ctDNA% and total cfDNA concentration were correlated (R2=0.55), association with OS was stronger for ctDNA% than cfDNA concentration (stratified at median; HR: 2.9 (2.3-3.7), p<0.001 vs HR: 2.1 (1.7-2.6), p<0.001). Conclusions: In a large cohort of treatment-naïve mCRPC pts, ctDNA% prior to 1L treatment provided strong prognostic information independent of known clinical factors. These data further demonstrate the multipronged clinical utility of ctDNA-based profiling for actionable genomic alterations.[Table: see text]

Real-world (RW) outcomes for advanced non-small cell lung cancer (aNSCLC) patients (pts) with EGFR exon 19 deletions (x19del) stratified by deletion size.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9591-9591
Author(s):  
Sai-Hong Ignatius Ou ◽  
Russell Madison ◽  
Tamara Snow ◽  
Jeremy Snider ◽  
Margaret Elizabeth McCusker ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Comprehensive Genomic Profiling ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Egfr Tki ◽  
Egfr Tkis

9591 Background: EGFR x19dels are well-established targetable drivers in NSCLC. Historically x19dels have been treated as a single group, but it’s unclear whether responses vary for distinct subtypes. We compared demographic, clinical and genomic characteristics as well as outcomes to EGFR tyrosine kinase inhibitors (TKIs) for aNSCLC pts with x19dels of varying lengths using a RW Clinico-Genomic Database (CGDB). Methods: Eligible pts had a diagnosis of aNSCLC, received care within the Flatiron Health network between 1/2011-9/2019, and had comprehensive genomic profiling (CGP) by Foundation Medicine. Clinical characteristics, treatment history and RW progression were obtained via technology-enabled abstraction as previously described (Singal G, JAMA 2019). x19del length was evaluated for association with overall survival (OS) and RW progression-free survival (rwPFS) with Kaplan-Meier analysis and unadjusted/adjusted (practice type, gender, age at TKI start, EGFR TKI type, race) hazard ratios (HR/aHR) from Cox proportional hazards models adjusted for survival bias. Results: Among 6,577 aNSCLC pts, EGFR x19dels were detected in 336 cases (5%). E746_A750del was the most frequent (214; 64%) and generally 5 amino acid (aa) deletions (x19del-5) were the most common (241; 72%). Other deletions (x19del-other) of 6 (61; 18%), 3 (20; 6%), 4 (11; 3%) or 8 aa (3; 1%) were also observed. Among pts treated with 1st-line EGFR TKI monotherapy after CGP, the x19del-5 (n = 70) cohort was more frequently female compared to x19del-other (n = 27) (90% vs 59%, p = 0.001). No statistically significant differences in the frequency of co-occurring alterations were observed, specifically for genes associated with response to EGFR TKI response such as CTNNB1 (14% vs 19%) and PIK3CA (10% vs 15%). 1st line EGFR TKIs used were similar for x19del-5 vs x19del-other (43% vs 41% osimertinib, 30% vs 37% erlotinib, 24% vs 22% afatinib, 3% vs 0% gefitinib). x19del-5 pts had similar median rwPFS (10.6 vs 10.6 months, HR: 0.73 [0.41-1.28], aHR:0.78 [0.38-1.59]) and median OS (29.2 vs 24.9 months, HR: 0.64 [0.32- 1.29], aHR: 0.75 [0.32-1.75]) compared to x19del-other. Conclusions: In a RW CGDB of 336 aNSCLC pts with EGFR x19dels, 5 aa x19dels were most common (71%) and 29% of cases had 3, 4, 6 or 8 aa x19dels . For pts included in the treatment cohort, no significant differences in rwPFS or OS were observed. These results suggest that x19del length does not significantly impact clinical outcomes to 1st-line EGFR TKIs.

The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

2021 ◽  
pp. 1-9
Author(s):  
Leonard Naymagon ◽  
Douglas Tremblay ◽  
John Mascarenhas
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Significant Difference ◽  
The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

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