An observational study of patients with advanced melanoma receiving pembrolizumab in a real-world U.S. community oncology practice.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21015-e21015
Author(s):  
Charles Lance Cowey ◽  
Frank Xiaoqing Liu ◽  
Jenny Black-Shinn ◽  
Kendall Lee Stevinson ◽  
Marley Boyd ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Brain Metastases ◽  
Real World ◽  
Performance Status ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Ecog Performance Status ◽  
Study Results ◽  
Line Of Therapy ◽  
Oncology Practice

e21015 Background: PD-1 monoclonal antibodies are promising immunotherapies approved for treatment of patients (pts) with advanced melanoma. As the first US FDA approved PD-1 antibody, pembrolizumab (pembro) has demonstrated efficacy and safety in clinical trial settings. However, patterns of real world utilization and pt outcomes associated with pembro are limited. Methods: Adult pts with advanced melanoma who initiated pembro between 9/1/ 2014-3/31/2016 were identified retrospectively fromelectronic health records (EHR) of McKesson Specialty Health and followed through 9/ 30/2016. Pts in clinical trials were excluded. Demographic, disease, treatment characteristics and reasons for treatment discontinuation of pembro were abstracted from structured data elements of the EHR with further supplementation of unstructured data within the patient chart (progress notes, radiology scan reports). Overall survival (OS) and physician-reported progression free survival (PFS) from pembro initiation were analyzed using Kaplan Meier analysis. Results: 182 pts, with a median follow-up of 9.9 mos (range = 0.0-25.0), were included. Median age at pembro initiation was 66.0 yrs; 30.8% had an elevated lactate dehydrogenase (LDH); 23.6% had brain metastases and 65.4% had an ECOG performance status of 0 or 1. The most common reason for pembro discontinuation was progression (45.5%) followed by treatment-related toxicity (24.4%). In the overall population, median PFS from pembro initiation was 4.2 mos (95% CI = 3.2-5.3). Median OS was 19.4 mos (14.0-NR) with 12 and 24-month survival probabilities of 61.4% (95% CI = 53.4-68.5) and 43.9% (95% CI = 31.1-55.9). In multivariable analyses, characteristics predictive of worse survival included receipt of pembro at a later line of therapy (HR = 3.36, p = 0.0013 for 3L+), presence of brain metastases (HR = 2.67, p = 0.0007) and elevated LDH (HR = 4.10, p < 0.0001). Conclusions: The study results are consistent with those from pembro clinical trials (KeyNote001) and are in support of the effectiveness of pembro in real world treatment of advanced melanoma. Presence of brain metastases, elevated LDH, and use of pembro 3L+ were associated with worse survival outcome.

Real-world outcomes of advanced melanoma patients treated with pembrolizumab who have failed prior lines of therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21031-e21031
Author(s):  
Wanmei Ou ◽  
Emilie Taymor ◽  
Scott J. Diede ◽  
Eric D. Whitman
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Performance Status ◽  
Clinical Effectiveness ◽  
Advanced Melanoma ◽  
Limited Information ◽  
Clinical Practices ◽  
Effective Treatment Option ◽  
Ecog Performance Status ◽  
Starting Point

e21031 Background: Pembrolizumab (PEM), a humanized antibody targeting programmed death-1 receptor, has been approved by FDA for the treatment of patients (pts) with advanced melanoma (AM) in the US since 2014. Real-world (RW) data supports the clinical effectiveness of 1L use of PEM, but there is limited information of PEM later line use. The study examined the RW outcomes of pts treated with PEM who have failed prior lines of therapy in US oncology clinical practices. Methods: Flatiron Health longitudinal database was used to identify adult pts with AM who received ≥1 dose of PEM in second line (2L) or later (3L+) between September 4, 2014 and May 31, 2017. Pts were followed up to May 31, 2018. Pts in clinical trials were excluded. Pt demographic, treatment, and clinical characteristics were described. Time on treatment (ToT) and overall survival (OS) were analyzed using the Kaplan Meier (KM) method, with the first dose of PEM as the starting point. Results: Two hundred thirty-six pts were included in the analysis, of which there were 171 2L and 65 3L+. Overall, median age at PEM initiation was 66 years; most were male (66.1%) and Caucasian (95.4%). 41.1% of pts’ tumors were confirmed BRAF mutant; 49.6% of pts’ tumors were confirmed BRAF wildtype; the rest was not tested or indeterminate. When data were available, 26.2% had an elevated lactate dehydrogenase (> ULN), 24.6% had brain metastases, and 25.5% had an ECOG performance status of > 1. At the time of analysis, pts were followed for a median of 12.5 months (mo, range, 0.1-44.6). Overall median ToT was 4.4 mo (95% CI, 3.5-5.3), with 4.7 and 4.4 mo in 2L and 3L+, respectively. Overall median OS was 16.8 mo (95% CI, 12.2-25.9), with 16.8 and 18.9 mo for 2L and 3L+ respectively. 1-year and 2-year survival, using the KM method, was 58.0% (95% CI, 51.2-64.1; 2L, 57.4%; 3L+, 59.6%) and 44.7% (95% CI, 37.9-51.3; 2L, 44.3%; 3L+, 46.1%) respectively. Conclusions: The study reports RW use of PEM in a large cohort of pts with AM who have failed initial therapy in US oncology clinical practices, with a heterogeneous study population compared to clinical trials. The findings of OS based on RW use suggest PEM is an effective treatment option for patients in later lines of therapy.

Initial experience of TAS-102 chemotherapy in Australian patients with chemorefractory metastatic colorectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 71-71
Author(s):  
Azim Jalali ◽  
Hui-Li Wong ◽  
Rachel Wong ◽  
Margaret Lee ◽  
Lucy Gately ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Febrile Neutropenia ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Performance Status ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Performance Status ◽  
Number Of Patients

71 Background: For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. In Australia, TAS-102 was initially made available locally through patients self-funding, later via an industry sponsored Medicine Access Program (MAP) and then via the Pharmaceutical Benefits Scheme (PBS). This study aims to investigate the efficacy and safety of TAS-102 in real world Australian population. Methods: A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to all TRACC patients and those enrolled in the registration study (RECOURSE). Results: Across 13 sites, 107 patients were treated with TAS-102 (non-PBS n = 27, PBS n = 80), The median number of patients per site was 7 (range: 1-17). The median age was 60 years (range: 31-83), compared to 67 for all TRACC patients and 63 for RECOURSE. Comparing registry TAS-102 and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease and 39% vs 49% were RAS wild type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median clinician assessed progression-free survival was 3.3 compared to RECIST defined PFS of 2 months in RECOURSE study, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths in the real-world series, where TAS102 dose at treatment initiation was at clinician discretion. In the RECOURSE study there was a 4% febrile neutropenia rate and one treatment-related death. Conclusions: TRACC registry patients treated with TAS102 were younger than both TRACC patients overall and those from the RECOURSE trial. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS. However overall survival outcomes achieved with TAS102 in real world patients were comparable to findings from this pivotal trial with an acceptable rate of major adverse events.

scholarly journals 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

2019 ◽  
Vol 11 ◽  
pp. 175883591987112 ◽  
Author(s):  
Changhoon Yoo ◽  
Hyeon-Su Im ◽  
Kyu-pyo Kim ◽  
Do-Youn Oh ◽  
Kyung-Hun Lee ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Real World ◽  
Performance Status ◽  
Objective Response ◽  
Real Life ◽  
Progression Free Survival ◽  
Real World Data ◽  
Ecog Performance Status ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Liposomal Irinotecan

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.

A multicentered population-based analysis of outcomes of patients with metastatic renal cell carcinoma (mRCC) who do not meet eligibility criteria for clinical trials.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 353-353 ◽  
Author(s):  
Daniel Yick Chin Heng ◽  
Toni K. Choueiri ◽  
Jae-Lyun Lee ◽  
Lauren Christine Harshman ◽  
Georg A. Bjarnason ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Clear Cell ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
Exclusion Criteria ◽  
Eligibility Criteria ◽  
Number Of Patients

353 Background: Clinical trials have strict eligibility criteria to maintain internal validity. These criteria exclude many patients to whom the trial results are later applied to in clinical practice. Patients that do not meet eligibility criteria are poorly characterized. Methods: mRCC patients treated with VEGF targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky Performance Status (KPS) < 70%, brain metastases, non-clear cell histology, hemoglobin ≤ 9 g/dL, creatinine > 2x the upper limit of normal, platelet count of < 100x103/uL, neutrophil count < 1500/mm3 or corrected calcium ≤ 12 mg/dL. Results: 894/2076 (43%) patients were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression free survival (PFS) and median overall survival of first-line targeted therapy were 21% vs 29%, 5.2 vs 8.8 months and 14.5 vs 28.8 months (all p < 0.0001), respectively. Second-line PFS (if applicable) was 3.2 months in the trial ineligible vs 4.4 months in the trial eligible patients (p = 0.0074). When adjusted by the Heng et al prognostic categories, the hazard ratio for death between trial ineligible vs trial eligible patients was 1.621 (95% CI = 1.431–1.836, p < 0.0001). If only KPS, brain metastases and non-clear cell histology were used as exclusion criteria, 672 (32%) patients were excluded and the results were similar. Conclusions: The number of patients that are ineligible for clinical trials is high and their outcomes are inferior. Designing more inclusive clinical trials for this “ineligible” patient population are needed. [Table: see text]

Bevacizumab in combination with first-line metastatic chemotherapy in patients with advanced nonsquamous non-small cell lung cancer (NSCLC): Results from the cohort study EOLE.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18005-e18005
Author(s):  
Christos Chouaid ◽  
Roland Schott ◽  
Lionel Falchero ◽  
Franck Bonnetain ◽  
Julien Neaume ◽  
...  
Keyword(s):  
Cohort Study ◽  
Performance Status ◽  
Locally Advanced ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Large Cell Carcinoma ◽  
First Line ◽  
Ecog Performance Status ◽  
Study Results ◽  
Chi2 Test

e18005 Background: EOLE, a large cohort of 423 patients included in 1 year (July 2010 – July 2010) with locally advanced, metastatic or recurrent non-squamous NSCLC, aimed to describe the targeted population receiving first-line bevacizumab (Bev) in addition to chemotherapy with regards to progression-free survival, overall survival, safety and quality of life in real clinical practice. Methods: Patients who received physician’s choice of 1st-line Bev-containing treatment were included in this cohort study. Results: This analysis describes the inclusion data of 417 patients consisting of adenocarcinoma (92%), large cell carcinoma (4%), undifferentiated carcinoma in predominantly non-squamous (3%), bronchoalveolar carcinoma (1%). Patient characteristics were as follow: the median age being 60 (years) [32; 84], more males than females (68%), 40% had a baseline ECOG Performance Status (PS) 0, 47% of PS 1 and 12% of PS 2, most patients had Stage IV disease (91%), 13% of patients had never smoked. Tumor location was reported as central for 17% of patents and among them 4% was in contact with the large vessels. For 3% of the lesions a cavitation was notified; and 20% of included patients had brain metastases. The main comorbidities at the inclusion were: cardiovascular (45%), arterial thromboembolic and /or venous (20%) with pulmonary embolism (3%); related to the tumor lesion - bloody sputum (4%) and hemoptysis (1%). 68% of patients have received the dose of Bev 7.5mg/kg q3w; for 49% of patients Bev was combined with cisplatin/pemetrexed, 24% with carboplatin/paclitaxel, 13% with carboplatin/pemetrexed and 7% with cisplatin/gemcitabine. The EGFR mutation analysis was carried out for about 50% of patients. Conclusions: Compared to AVAil and SAil studies, EOLE cohort included more patients classified as having: a baseline PS of 2 (p <0.0001, Fisher test), a never smoked status (p<0.0001, chi2 test) and an adenocarcinoma (92%) (p<0.0001, chi2 test). Around a half of included patients received combination Bev - cisplatin /pemetrexed.

Different efficacy of osimertinib in pre-TKI treated NSCLC patients with brain metastases harboring EGFR exon 19del and L858R mutant.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21667-e21667
Author(s):  
Xuanzong Li ◽  
Ruozheng Wang ◽  
Bing Zou ◽  
Dai Zhang ◽  
Jinming Yu ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Kinase Inhibitors ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Apparent Difference ◽  
Ecog Performance Status ◽  
Study Results ◽  
Egfr Mutant ◽  
Nsclc Patients

e21667 Background: Previous studies suggested that the efficacy of osimertinib was better in patients with epidermal growth factor receptor ( EGFR) exon 19 deletion (ex19del) than exon 21 Leu858Arg (L858R). However, the differential clinical outcomes of osimertinib in previous tyrosine kinase inhibitors (TKIs) treated non-small-cell lung cancer (NSCLC) patients with brain metastases (BrMs) according to the two different common EGFR genotypes remains undetermined. Methods: We retrospectively collected EGFR mutant (ex19del and L858R) NSCLC patients with BrMs and received osimertinib treatment between Jan 2016 and Feb 2019 in our hospital. Other eligible standards including Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, osimertinib 80mg monotherapy and neurologic symptoms existing was permitted to enroll in our study. Results: 78 patients with EGFR mutant NSCLC and BrMs were included in the study. EGFR mutation types were ex19del in 55% of patients (43/78) and L858R in 45% of patients (35/78). All of patients received at least one prior EGFR-TKI therapy, among which 46% (36/78) had gefitinib, 49% (38/78) had erlotinib, 19% (15/78) had icotinib. T790M status at osimertinib initiation was positive in 81% of patients (63/78), negative in 4% (3/78), unknown in 15% (12/78). The systemic objective response rate (ORR) was 46%. There was no apparent difference in systemic ORR (49% vs 43%, P = 0.598) between ex19del group and L858R group. The median progression free survival (PFS) and overall survival (OS) were 7.0 (range 4.7-9.3) and 18.8 (range 14.0-23.5) months for all patients. The median PFS in the ex19del and L858R subgroups was 9.1 (range 6.0-12.1) months and 5.3 (range 3.4-7.2) months, respectively ( P = 0.031). The median OS in the ex19del and L858R subgroups was 26.0 (range 13.7-38.3) months and 13.9 (range 7.7-20.2) months, respectively ( P = 0.033). Multivariate analysis identified L858R and ECOG PS 2 as poor independent predictors to the PFS and OS. Conclusions: The efficacy of osimertinib was associated with EGFR genotypes in pre-TKI treated NSCLC patients with BrMs, and L858R maybe an independent bad factor for long-term outcomes of osimertinib.

Real-world outcomes in patients (pts) with metastatic urothelial carcinoma (mUC) who received first- or second-line immunotherapies (IO) in the United States (US).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 457-457
Author(s):  
Marley Boyd ◽  
Srinivas Annavarapu ◽  
Gurjyot K. Doshi ◽  
Kentaro Imai ◽  
Eric Sbar ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Real World ◽  
Performance Status ◽  
The United States ◽  
Future Research ◽  
Second Line ◽  
Ecog Performance Status ◽  
Using Data ◽  
Line Of Therapy

457 Background: Benefit of IO (PD1 and PD-L1 inhibitors) for mUC was observed in clinical trials but real-world evidence for benefit and clinical outcomes is limited. Methods: This was a retrospective study of adult pts with mUC who initiated IO regardless of PD-L1 expression in the first- (1L cohort) or second-line (2L cohort) setting between 5/1/2016-1/31/2019 in the US Oncology Network (USON), a network of community oncology practices. Descriptive and Kaplan-Meier analyses to evaluate baseline characteristics, treatment patterns and clinical outcomes were conducted using data from USON’s electronic heath record. Results: Among 393 pts in the 1L cohort, median (range) age at IO initiation was 77 (42, 90+), 74% were male, 69% were White, and 19.1% and 4.1% had ECOG performance status (PS) 2 and 3/4, respectively. Among the 366 pts in the 2L cohort, median (range) age at IO initiation was 70 (29, 90+), 74% were male, 71% were White, and 19.7% and 1.4% had ECOG PS 2 and 3, respectively. Median (range) follow-up durations from IO initiation were 4.2 (0, 34.1; 1L cohort) and 4.1 (0, 31.3; 2L cohort) months (mo), during which time 43.1% (1L cohort) and 44.4% (2L cohort) of pts died. Median overall survival (OS) from IO initiation (95% confidence interval [CI]) was 10.6 (9.7, 13.2) mo for the 1L cohort and 9.4 (7.1, 11.5) mo for the 2L cohort; 1-year survival probabilities (95% CI) were 46.6% (40.1%, 52.8%; 1L cohort) and 43.4% (36.8%, 49.8%; 2L cohort). By the end of the follow-up, 48.1% of 1L pts and 47.8% of 2L pts were alive and did not advance to next line of therapy, and 13.5% of 1L and 13.4% of 2L cohort pts advanced to the next line of therapy. Median (95% CI) treatment durations were 2.6 (2.1, 2.9) and 2.8 (2.2, 3.5) mo for the 1L and 2L cohorts, respectively; 6-mo ongoing treatment probabilities (95% CI) were 26.6% (22.2%, 31.2%; 1L cohort) and 31.4% (26.4%, 36.4%; 2L cohort). Conclusions: OS of pts in the real world receiving 1L and 2L IO appears consistent with clinical trial results, although survival follow-up is limited. A minority of pts received post-IO therapy. Future research should examine influence of pt characteristics and PD-L1 expression on treatment choice and outcomes.

scholarly journals Real-World Data for Lenvatinib in Hepatocellular Carcinoma (ELEVATOR): A retrospective multicenter study

Liver Cancer ◽  
2022 ◽  
Author(s):  
Sabrina Welland ◽  
Catherine Leyh ◽  
Fabian Finkelmeier ◽  
André Jefremow ◽  
Kateryna Shmanko ◽  
...  
Keyword(s):  
Overall Survival ◽  
Real World ◽  
Median Overall Survival ◽  
Performance Status ◽  
Progression Free Survival ◽  
Inclusion Criteria ◽  
First Line ◽  
Ecog Performance Status ◽  
Free Survival ◽  
First Line Treatment

Background Lenvatinib is approved as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). The efficacy of lenvatinib in Caucasian real-world patients is insufficiently defined. The purpose of this study was to evaluate the efficacy of lenvatinib in a multi-center cohort (ELEVATOR) from Germany and Austria. Methods A retrospective data analysis of 205 patients treated with first-line systemic lenvatinib at 14 different sites was conducted. Overall survival, progression free survival, overall response rate and adverse event rates were assessed and analyzed. Results Patients receiving lenvatinib in the real-world setting reached a median overall survival of 12.8 months, which was comparable to the results reported from the REFLECT study. Median overall survival (mOS) and progression free survival (mPFS) was superior in those patients who met the inclusion criteria of the REFLECT study compared to patients who failed to meet the inclusion criteria (mOS 15.6 vs 10.2 months, HR 0.55, 95% CI 0.38-0.81, p=0.002; mPFS 8.1 vs 4.8 months HR 0.65, 95% CI 0.46-0.91, p=0.0015). For patients with an impaired liver function according to the Albumin-Bilirubin (ALBI) grade, or reduced ECOG performance status ≥2, survival was significantly shorter compared to patients with sustained liver function (ALBI grade 1) and good performance status (ECOG performance status 0), respectively (HR 1.69, 95% CI 1.07-2.66, p=0.023; HR 2.25, 95% CI 1.19-4.23, p=0.012). Additionally, macrovascular invasion (HR 1.55, 95% CI 1.02-2.37, p=0.041) and an AFP ≥200 ng/mL (HR 1.56, 95% CI 1.03-2.34, p=0.034) were confirmed as independent negative prognostic factors in our cohort of patients with advanced HCC. Conclusion Overall, our data confirm the efficacy of lenvatinib as first-line treatment and did not reveal new or unexpected side effects in a large retrospective Caucasian real-world cohort, supporting the use of lenvatinib as meaningful alternative for patients that cannot be treated with IO-based combinations in first-line HCC.

Phase II trial of sunitinib in bevacizumab-refractory metastatic renal cell carcinoma (mRCC): Updated results and analysis of circulating biomarkers

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5035-5035 ◽  
Author(s):  
D. J. George ◽  
M. D. Michaelson ◽  
J. E. Rosenberg ◽  
R. M. Bukowski ◽  
J. A. Sosman ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Clinical Response ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cross Resistance ◽  
Ecog Performance Status ◽  
Study Results ◽  
Pre Treatment

5035 Background: Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor with antiangiogenic and antitumor activity. This study evaluated the safety and activity of sunitinib in mRCC patients (pts) previously treated with the VEGF-neutralizing antibody, bevacizumab. Levels of angiogenic biomarkers, including plasma VEGF and soluble VEGFR-3 (sVEGFR-3), were assessed for predictive significance with clinical response. Methods: Pts were required to have mRCC with disease progression following bevacizumab- based therapy, measurable disease, ECOG performance status 0 or 1, and adequate organ function. Pts were treated with sunitinib 50 mg daily in 6-week cycles (4 weeks on, followed by 2 weeks off). The primary endpoint was objective response according to RECIST. Plasma VEGF and sVEGFR-3 levels were measured in pre-treatment samples and at multiple timepoints on study. Results: A total of 61 pts were enrolled. The objective partial response rate was 23% (95% CI: 13%, 36%); 35 pts (57%) demonstrated stable disease. The median duration of response was 36 weeks (95% CI: 26, NA) and progression-free survival was 30 weeks (95% CI: 18, 34). Plasma VEGF levels increased from baseline (3-fold mean elevation), while plasma sVEGFR-3 levels decreased from baseline (40% mean reduction). Pre-treatment VEGF levels were significantly higher in pts (n=34) with <10 weeks between cessation of bevacizumab and start of sunitinib (p<0.001); ELISA specificity suggests that detected VEGF is not bevacizumab-bound. Pre-treatment sVEGFR-3 levels were significantly lower at baseline in responding pts vs. non-responding pts (p<0.0318). A greater reduction in sVEGFR-3 levels was seen in responding pts vs. non-responding pts (p<0.10). Pretreatment VEGF and VEGF fold-changes did not differ according to clinical response. Conclusions: Sunitinib has significant antitumor activity in bevacizumab-refractory mRCC pts, suggesting absence of cross-resistance between bevacizumab and sunitinib. Biomarkers including plasma VEGF and sVEGFR-3 may have predictive potential in sunitinib-treated patients. No significant financial relationships to disclose.

Real world treatment patterns of first-line combination therapies among BRAF+ metastatic melanoma patients.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 197-197
Author(s):  
Sameer Ghate ◽  
Jackson Tang ◽  
Zhiyi Li ◽  
Antonio Reis Nakasato
Keyword(s):  
Metastatic Melanoma ◽  
Real World ◽  
Performance Status ◽  
Treatment Patterns ◽  
Toxic Effects ◽  
First Line ◽  
Ecog Performance Status ◽  
Status Score ◽  
Study Results ◽  
Performance Status Score

197 Background: For patients (pts) with metastatic melanoma (MM) and BRAF V600 mutation (BRAF+), options for first-line (1L) systemic combination therapy include immunotherapy (IO) or targeted therapy (TT). This study describes real world treatment patterns among BRAF+ MM pts treated with 1L ipilimumab+nivolumab (I+N) or dabrafenib+trametinib (D+T). Methods: This retrospective observational analysis used Flatiron Health’s electronic health record-derived database from Oct 2015 - Jul 2016. Oct 2015 was chosen as the start date as both combo use of I+N and D+T had been approved by the FDA. Pts were aged ≥18 years with a MM diagnosis, tested BRAF+ prior to therapy, and treated with either I+N or D+T as 1L therapy. Baseline demographic and clinical characteristics, and treatment patterns were collected from structured data and unstructured data in physician notes, and were descriptively assessed. Kaplan-Meier (KM) analysis measured time to discontinuation. Statistical inferences were not planned in this study. Results: Among 76 BRAF+ pts, 62% (47) were treated with D+T as 1L, and 38% (29) were treated with I+N as 1L. Compared to D+T pts, lower proportion of I+N pts had a history of brain metastases (31% vs. 34%) and elevated ( > 333 IU/L) lactate dehydrogenase (10% vs. 19%), while a higher proportion of I+N pts reported ECOG performance status score of zero (38% vs. 23%). The two cohorts were similar in age, gender and baseline comorbidities. Discontinuation among D+T and I+N was 43% (20) and 48% (14) respectively. The primary reason for discontinuation was progression among D+T pts (10/20) vs. toxic effects of therapy among I+N pts (8/14). KM median time to discontinuation was 213 days for D+T pts vs. 196 days for I+N pts. 55% of I+N pts did not complete full induction of 4 doses of ipilimumab, citing toxic effects of therapy. Conclusions: 1L D+T patients had higher tumor burden, elevated LDH levels, and higher ECOG performance status score, but lower discontinuation rate and longer time to treatment discontinuation relative to BRAF+ 1L I+N pts.

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