Prolonged Administration of Arsenic Trioxide (Trisenox®) for Patients with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) at MD Anderson Cancer Center: A Phase II Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4731-4731
Author(s):  
Miloslav Beran ◽  
Srdan Verstovsek ◽  
Steven M. Kornblau ◽  
Elihu H. Estey ◽  
Francis Giles ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Stable Disease ◽  
Chromosomal Abnormalities ◽  
Previous Treatment ◽  
Response Duration ◽  
Outpatient Setting ◽  
Prolonged Treatment ◽  
Cancer Center ◽  
Prolonged Administration ◽  
Grade 3

Abstract The value of prolonged administration of arsenic trioxide (ATO) was examined in patients (pts) with MDS and CMML. ATO (0.25 mg/kg) was given intravenously over 1 hour daily for five days followed by 0.25 mg/kg twice weekly for 11 weeks. Pts were assessed at 4 weeks, at the end of the first course, and then monthly. Pts with stable disease were eligible for further courses. The study included 14 RBC transfusion-dependent MDS pts (6 RA/RARS, 8 RAEB; 12 IPSS risk Low/Int1, 2 Int2/High), and 3 CMML pts. Median age was 67 years (range 46–84). Six pts had a history of previous treatment other than supportive care. 16 pts were evaluable for toxicity and response. One pt received 3 courses, 3 received 2 courses, and 13 received 1 course. Hematologic responses (IWG criteria) were observed in 4 pts (25%) and 9 (6 MDS,3 CMML) had stable disease: FAB Type of response Time to response Duration RA Minor erythroid 2 months 3 mo, RBC independence RAEB Major neutrophil and platelet 2 mo 3 mo RAEB BM blast decrease 18% to <5% 1 mo 14 mo, stable pancytopenia RAEB Hematologic/cytogenetic CR 1 mo 6 mo Hematologic/cytogenetic CR was achieved in one pt: a 76 year old male, RAEB-2, Int 2, complex chromosomal abnormalities, who had previously failed thalidomide for 6 months and thalidomide + cyclosporin A for 3 months. Of the 3 CMML pts, one had transient reduction of absolute monocyte counts during each of 2 courses; all 3 had stable disease. In 24 courses there were 6 febrile episodes in 4 patients, requiring admission, all in pts with pre-existing neutropenia; 1 Grade 3 and 1 Grade 4 thrombocytopenia, 1 Grade 3 neutropenia, all requiring dose modification; 1 episode of accelerated functional cardiac rhythm; and 1 anemia-precipitated congestive heart failure, which was unlikely related to the drug. There were 22 episodes of Grade 1 or 2 drug-related toxicities. Four responses of 3–7+ mo. duration were observed, including 1 CR, suggesting activity in an as yet undefined subgroup of MDS pts. No benefit of prolonged treatment was documented. ATO was safe in this outpatient setting for elderly patients. Observed low toxicity and documented activity support future trials of ATO in combination with other agents in treatment of MDS.

Randomized phase II trial of capecitabine versus capecitabine, low molecular weight heparin, and prednisone in refractory colorectal carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15126-e15126 ◽  
Author(s):  
E. Mak ◽  
C. Townsley ◽  
R. Buckman ◽  
E. Chen ◽  
L. Lopez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Stable Disease ◽  
Previous Treatment ◽  
Randomized Phase Ii ◽  
Common Grade ◽  
Hand Foot Syndrome ◽  
Grade 3

e15126 Background: Capecitabine is widely used in the treatment of advanced colorectal cancer. Continuous low dose chemotherapy has been postulated to have anti-angiogenic effects discrete from its anti-proliferative effects on tumors (metronomic therapy). Dalteparin and prednisone have also been implicated in inhibiting tumour angiogenesis and hypothesized to have additive benefit to chemotherapy. This randomized phase II study examined the additive effect of dalteparin and prednisone with capecitabine in metastatic colorectal cancer. Methods: Patients with metastatic colorectal cancer were randomized to either capecitabine (C) 2,500 mg/m2 in divided doses from days 1–14 in a 3-week cycle or capecitabine with dalteparin and prednisone (CDP). There was no restriction on previous treatment, other than no prior capecitabine. Dalteparin was given at 5,000 units once daily subcutaneously, and prednisone orally 10 mg daily, both on a continuous basis. Thirty patients were planned for accrual in each arm with interim analysis when accrual reached fifteen in each arm. The primary end-point was disease control defined as treatment response or stable disease >4 months. Radiological evaluation was performed every 6 weeks. Treatment was discontinued if patients had progressive disease or intolerable toxicity. Results: Thirty patients were recruited. Fourteen patients had received ≥3 previous regimens (median 3 (C), 2 (CDP)). Median performance statuses were ECOG 1 (C) and 0 (CDP). Nine patients achieved stable disease greater than 6 months (5 (C)/4 (CDP)). There was no statistical difference in the median survival time and time-to- progression for the two groups (11.1 mth (C)/15.8 mth (CDP); 3.2 mth (C)/2.8 mth (CDP)). The commonest toxicities overall were myelosuppression and hand-foot syndrome (HFS). The most common Grade 3+ adverse events were HFS (6 patients) and diarrhea (4 patients). Conclusions: The combination of dalteparin, prednisone and capecitabine did not improve disease control over that seen with capecitabine in refractory metastatic colorectal cancer. No significant financial relationships to disclose.

scholarly journals Reversible infertility in male dog following prolonged treatment of Malassezia dermatitis with ketoconazole

2021 ◽  
Vol 63 (1) ◽  
Author(s):  
Anna Domosławska ◽  
Sławomir Zduńczyk
Keyword(s):  
Adverse Effects ◽  
Testosterone Level ◽  
Antifungal Agent ◽  
Sperm Quality ◽  
Previous Treatment ◽  
Prolonged Treatment ◽  
Prolonged Administration ◽  
Case Presentation ◽  
Low Testosterone ◽  
Possible Cause

Abstract Background Ketoconazole, an antifungal agent, adversely affects spermatogenesis in rodents, but knowledge on adverse effects of prolonged administration of ketoconazole on the fertility of male dogs is lacking. A case of reversible infertility with azoospermia in a male American Staffordshire terrier treated with ketoconazole is reported here. Case presentation A seven-year old male American Staffordshire terrier treated for 3 months with ketoconazole for a persistent Malassezia dermatitis displayed reduced libido and mating of 3 bitches had been unsuccessful. The dog was presented at the clinic 40 days after the treatment had been stopped. At first presentation, low libido and complete absence of sperm in the ejaculate (azoospermia) associated with low testosterone level were found. Repeated examinations revealed that sperm quality and testosterone level had restored 100 days after ketoconazole had been withdrawn. Thereafter, the dog successfully mated 2 bitches. Conclusion The treatment with ketoconazole for 3 months may have led to reversible infertility characterized by azoospermia. Therefore, owners of stud dogs should be informed of this risk prior to initiating such treatment and in case of infertility, previous treatment with ketoconazole should be considered as a possible cause.

Phase I study of oral irinotecan and temozolomide in children with relapsed high-risk neuroblastoma: A New Approach to Neuroblastoma Therapy (NANT) Consortium study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9567-9567
Author(s):  
L. M. Wagner ◽  
J. G. Villablanca ◽  
C. F. Stewart ◽  
K. R. Crews ◽  
M. A. O'Shaughnessy ◽  
...  
Keyword(s):  
High Risk ◽  
Phase I ◽  
Stable Disease ◽  
Single Agent ◽  
Previous Treatment ◽  
Maximum Tolerated Dose ◽  
New Approach ◽  
Treatment Regimens ◽  
Heavily Pretreated ◽  
Grade 3

9567 Background: Irinotecan (IRN) and temozolomide (TEM) have single-agent activity and schedule-dependent synergy against neuroblastoma. Because intravenous IRN is costly and inconvenient, especially with protracted scheduling common in pediatric trials, we sought to determine the maximum tolerated dose (MTD) of oral IRN combined with TEM in children with recurrent/resistant high-risk neuroblastoma, using the antibiotic cefixime to reduce IRN-associated diarrhea. Methods: Patients received oral TEM on days 1–5 and oral IRN on days 1–5 and 8–12, with courses repeated every 21 days. Oral cefixime 8 mg/kg (max 400 mg/day) was started on day -5 and continued daily. Results: Fifteen patients (median age 7 years, range 2–22) with a median of 3.5 previous treatment regimens were evaluable for toxicity and have to date received 71 courses (median 2, range 1–19+). Neutropenia and thrombocytopenia were dose-limiting in the first 6 patients, and TEM was reduced from 100 to 75 mg/m2/day for all subsequent patients. IRN was then escalated from 30 to 60 mg/m2/day. First-course grade 3 diarrhea was dose-limiting in 1 of 6 patients treated at the IRN MTD of 60 mg/m2/day. Other toxicities were mild and reversible. No grade 4 therapy-related toxicity occurred in 27 courses administered at the MTD. The median SN-38 lactone AUC at this dose was 72 ng*hr/ml, similar to that reported with protracted intravenous IRN at the single-agent MTD. Of 14 patients evaluable for response, one with measurable nodal disease had a very good partial response through 6 courses. Six additional patients had stable disease for a median of 7.5 courses (range 6–19+). Two patients remain on study after 10 and 19 courses. Conclusions: This combination was well tolerated in heavily-pretreated children with resistant neuroblastoma, and 7 (50%) of 14 evaluable patients had response/stable disease for 6 or more courses in this Phase I trial. This all-oral regimen was feasible and resulted in favorable SN-38-lactone exposures. The dose recommended for further study in this patient population is TEM 75 mg/m2/day plus IRN 60 mg/m2/day when given with cefixime. No significant financial relationships to disclose.

Oxaliplatin plus continuous infusion topotecan: First stage of an ongoing phase II study for recurrent ovarian cancer: A New York Cancer Consortium study (#N01-CM62204)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5556-5556
Author(s):  
N. LaNatra ◽  
H. Hochster ◽  
F. Muggia ◽  
S. V. Blank ◽  
J. Curtin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
New York ◽  
Phase I ◽  
Continuous Infusion ◽  
Stable Disease ◽  
Response Duration ◽  
Recurrent Ovarian Cancer ◽  
Good Tolerability ◽  
Median Response ◽  
Grade 3

5556 Background: Topoisomerase-1 inhibitors and platinums are active in ovarian cancer. Our prior series described infusional topotecan as less myelosuppressive than bolus and more easily combined with oxaliplatin than cisplatin. An NYU phase I study of the combination in previously treated ovarian cancer patients (pts) showed promising activity and good tolerability (Hochster H, Gynecol Oncol 2008). Methods: Ovarian cancer pts treated with 1–2 prior regimens (1 platinum/taxane regimen, no topotecan) were treated with oxaliplatin 85 mg/m2 day 1, 15 and topotecan (0.4 mg/m2/day) continuous infusion x 14 days every 4 weeks (wks). Platinum resistant (stratum I = 10) and sensitive (stratum II = 17) pts are included in this two-stage trial (n = 52) to evaluate overall response rate (ORR) and toxicities. Results: From January 2006 to November 2008, 27 pts entered. Median age was 61 (37–79). Fifteen pts had 1 prior regimen and 12 pts had 2. Five pts discontinued before 2 cycles (3 for predefined toxicity, 2 by pt/physician choice). 102 cycles of chemotherapy were given (median 4, [1–6]). Grade 3/4 toxicities included thrombocytopenia (37% grade 3, 19% grade 4), neutropenia (37% grade 3, 11% grade 4), anemia (15% grade 3), neuropathy (7% grade 3), diarrhea (4% grade 3), transaminitis (4% grade 3), and fatigue (7% grade 3). Twenty-one pts had day 15 oxaliplatin held, 10 pts required dose reductions, and 21 pts had treatment delays mainly from thrombocytopenia. No pts had neutropenic fever. Twenty-one pts are now evaluable. Stratum I had 1 complete and no partial responses, 5 pts with stable disease and 2 with progressive disease. Stratum II had 3 complete and 6 partial responses, 4 pts with stable disease and none progressed. Median response duration is 41 wks (17–62); median duration of stable disease is 17 wks (4–70). Conclusions: Excluding thrombocytopenia, tolerance to this regimen confirms phase I results. In pts with creatinine clearances (CrCl) < 60 ml/min, the incidence of grade 3/4 thrombocytopenia was 75% versus 35 % for pts with CrCl > 60 ml/min. Pts with CrCl of 40–60 ml/min will now start topotecan 0.3 mg/m2/day x 14 days. Reaching our predefined ORR of at least 30% for stratum II and 20% for stratum I, the second stage of accrual has begun. [Table: see text]

Palliative chemotherapy in head and neck cancers: A tertiary care center experience with weekly paclitaxel and cetuximab.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16028-e16028
Author(s):  
Kumar Prabhash ◽  
Vanita Noronha ◽  
Amit Joshi ◽  
Vijay Patil ◽  
S Juvekar ◽  
...  
Keyword(s):  
Care Center ◽  
Tertiary Care ◽  
Single Agent ◽  
Haematological Toxicity ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Outpatient Setting ◽  
Weekly Paclitaxel ◽  
Best Response ◽  
Grade 3

e16028 Background: The concept of combination of paclitaxel and cetuximab is an intersesting prospect as both these agents have single agent acitivity, minimal toxicity and hold a biological rationale for combination. The aim of our study was to see the safety,efficacy and feasibility of administration of this combination in a outpatient setting. Methods: This was a retrospective analysis of the prospectively collected data, of patients offered weekly paclitaxel and cetuximab from May 2010-May 2011. The standard schedule of cetuximab along with 80 mg/m2 of weekly paclitaxel was administered till either disease progression or withdrawl of patient's consent. The toxicity profile was noted in accordance with CTCAE version 4.02 and response in accordance with RECIST criteria. SPSS version 16 has been utilized for analysis. Descriptive statistics are been presented and analyis of estimation of overall and progression free survival has been done with Kaplan-Meier survival method. Results: 42 patients with a median age of 52 years (35-81 years) were included. The KPS score was 60 in 1 (2.4%),70 in 11 (26.2%) and 80 in 30 patients(71.4%). Nearly half of our patients 22 (52.4%) had a primary in oral cavity. Except 3 (7.1%) patients rest all had received some form of previous treatment. The median event free period(EFP) from previous first line treatment was 231 days, it was below 180 days in 38.5% of patients. Best response observed was CR in 1 patient (2.4%), PR in 11 (26.2%), SD in 17 (40.5%) and PD in 13 (30.9%). Grade 3-4 skin changes were seen in 3 patients, grade 3-4 neuropathy was seen in 3 patients and there were no episodes of grade 3-4 gastrointestinal or haematological toxicity. The overall estimated median PFS and OS were 128 and 256 days. The median estimated PFS for patients with EFP less than 6 months versus more than 6 months was 115 and 165 days respectively (p = 0.132). Conclusions: The combination of paclitaxel and cetuximab was found to be safe, feasible and appears to be clinically beneficial.

scholarly journals PATH-19. MOLECULAR, HISTOLOGIC AND CLINICAL CHARACTERISTICS OF OLIGODENDROGLIOMAS: A MULTI-INSTITUTIONAL RETROSPECTIVE STUDY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii168-ii168
Author(s):  
Antonio Dono ◽  
Kristin Alfaro-Munoz ◽  
Yuanqing Yan ◽  
Carlos Lopez-Garcia ◽  
Zaid Soomro ◽  
...  
Keyword(s):  
Health Science ◽  
Cancer Center ◽  
Subtotal Resection ◽  
Adjuvant Radiation ◽  
Science Center ◽  
Who Grade ◽  
Pik3ca Mutations ◽  
Increased Risk ◽  
Significant Difference ◽  
Grade 3

Abstract In the 2016 WHO classification of CNS tumors, oligodendrogliomas are molecularly defined by IDH1 or IDH2 mutations and 1p/19q co-deletion. Some reports suggest that PI3K pathway alterations may confer increased risk of progression and poor prognosis in oligodendroglioma. However, factors that influence prognosis in molecularly defined oligodendroglioma (mOGD) have not been thoroughly studied. Also, the benefits of adjuvant radiation and temozolomide in mOGDs remain to be determined. 107 mOGDs diagnosed between 2008-2018 at the University of Texas Health Science Center at Houston (n= 39) and MD Anderson Cancer Center (n= 68) were included. A retrospective review of the demographic, clinical, histologic, molecular, and outcomes were performed. Median age at diagnosis was 37 years and 61 (57%) patients were male. There were 64 (60%) WHO Grade 2 and 43 (40%) WHO Grade 3 tumors. Ninety-five (88.8%) tumors were IDH1-mutant and 12 (11.2%) were IDH2-mutant. Eighty-two (77%) patients were stratified as high-risk: older than 40-years and/or subtotal resection (RTOG 9802). Gross-total resection was achieved in 47 (45%) patients. Treatment strategies included observation (n= 15), temozolomide (n= 11), radiation (n= 13), radiation with temozolomide (n= 62) and other (n= 6). Our results show a benefit of temozolomide vs. observation in progression-free survival (PFS). However, no benefit in PFS or overall survival (OS) was observed when comparing radiation vs. radiation with temozolomide. PIK3CA mutations were detected in 15 (14%) cases, and patients with PIK3CA-mutant mOGDs showed worse OS (10.7-years vs 15.1-years, p= 0.009). Patients with WHO Grade 3 tumors had shorter PFS but no significant difference in OS was observed compared to grade 2. Our findings suggest that mOGDs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS in temozolomide treated patients, adjuvant treatment with radiation or the combination of both, showed no significant advantage in terms of OS.

Rationale for the utilization of biological targeted agents (bTAs) in the treatment of metastatic colorectal cancer (mCRC), single tertiary cancer center experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15589-e15589
Author(s):  
Ivan Barrera ◽  
Yahia A. Lakehal ◽  
Tomas Kavan ◽  
Petr Kavan
Keyword(s):  
Bowel Perforation ◽  
Primary Objective ◽  
Cancer Center ◽  
Gi Symptoms ◽  
Significant Difference ◽  
Common Grade ◽  
Jewish General Hospital ◽  
Grade 3 ◽  
Physician Patient ◽  
Tertiary Cancer Center

e15589 Background: Worldwide treatment for 1st line (1LTx) mCRC included doublet or triple chemotherapy with or without bTAs. In Quebec, the anti-EGFR therapy (panitumumab or cetuximab) was only recently approved in this setting for patients RAS WT, Bevacizumab (B) not eligible. In this study we evaluated the rational and outcomes using bTAs. Methods: Retrospective study assessing mCRC pts treated with or without bTAs at any time throughout the course of therapy at the Jewish General Hospital between 2010-2018. Pts were divided in 3 groups according to their 1LTx for analysis: Chemotherapy alone (1LChA), Chemotherapy plus B (1LChB), and anti-EGFR with or without chemotherapy (1LaEGFR). The primary objective was to assess the rational of bTAs prescription based in 1LTx selection. Secondary objectives included safety, PFS and OS. Results: Among a total of 463 pts with mCRC; 196 pts (42.3%) received 1LChA, 246 pts (53.2%) 1LChB, and 21 pts (4.5%) 1LaEGFR respectively. 1LChA group, 51% omitted bTAs for physician-patient preferences, 96 pts (49%) had contraindications for B, and 79 pts (40.3%) were potentially candidates for aEGFR, but did not receive it. 152/196 (77.5%) pts continued to 2LTx and 34.8% received bTAs. As for the 3LTx, 78/196 (40%) received a treatment, 48.7% received bTAs. The most common grade 3-4 adverse events (AEs) were hypertension and bowel perforation in B, gastrointestinal (GI) symptoms and skin reaction (SR) in aEGFR. 1LChB group, 31 pts (12.6%) presented AEs related to B. 191/246 pts (77.6%) continued to 2LTx with 48 pts (25%) receiving ChB despite progression in 1LTx on this bTA and 19 pts (10%) receiving aEGFR. The most common AEs reported in 2LTx were GI symptoms and neuropathy. In 3LTx, 54/91pts (59.3%) received aEGFR therapy and 8 pts (14.8%) had SR AEs. 46 pts (18.6%) continued to 4LTx, 13/46 pts (28.2%) received aEGFR. 1LaEGFR group, the most common AEs were SR and GI symptoms. 11/21 pts (52.3%) continued to 2LTx; 5 pts (45.4%) switching bTA class and receiving ChB. 81% pts started treatment between 2017-2018 and had at least two contraindication criteria for. The median PFS for the 1LChA and 1LChB groups were 10 and 11.5 months, respectively, and were not statistically significant (p=0.22). The OS with 1LChA and 1LChB was 33.26 vs. 27.80 months (p=0.27). The PFS and OS between 1LChA and 1LaEGFR were 10 vs 11 months (p= 0.27) and 33.26 vs. 35.07 months (p=0.13). Conclusions: The outcome and tolerability of bTAs in mCRC appear similar in our institution and randomised trials. We were not able to detect any significant difference among the three groups of comparison. The 1LaEGFR available data in this subset of patients are limited. Our data highlights the importance of optimal therapeutic sequencing to prolong OS. Dedicated studies are needed in order to determine the best bTAs therapeutic strategy in mCRC.

The efficacy and safety of anlotinib in refractory/recurrent/advanced pediatric solid tumors: A retrospective study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11556-11556
Author(s):  
Suying Lu ◽  
Ye Hong ◽  
Huimou Chen ◽  
Liuhong Wu ◽  
Jia Zhu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Effective Treatment ◽  
Solid Tumors ◽  
Objective Response ◽  
Cancer Center ◽  
Treatment Schedule ◽  
Efficacy And Safety ◽  
Pediatric Solid Tumors ◽  
Hand Foot Syndrome ◽  
Grade 3

11556 Background: Refractory and recurrent advanced pediatric solid tumors are short of effective treatment and with a dismal outcome, thus an urgent need for novel and effective treatment. The aim of the study is to evaluate the efficacy and safety of anlotinib, a novel and oral multi-target receptor tyrosine kinase inhibitor, in refractory or recurrent advanced pediatric solid tumors. Methods: The retrospective, single-institutional, observed study was conducted in Sun Yat-sen University cancer center in China. Refractory, recurrent, or advanced pediatric solid tumors patients treated with anlotinib between 2018 to 2020 were evaluated. Results: Forty-one patients and thirty patients were enrolled in the study to evaluated efficacy and safety, respectively. The objective response ratio (ORR) was 12.2% (95%CI 1.7-22.7): complete response (n = 0) and partial response (n = 5) (Table). The disease control rate (DCR) was 65.9% (95%CI 50.7-81). The median progression-free survival (PFS) was 2.87 months (95%CI 0.86-4.88). According to anlotinib treatment schedule, all patients were divided into three groups: anlotinib monotherapy (A, n = 16), anlotinib combined with immune checkpoint inhibitor treatment (A + ICI, n = 6), anlotinib combined with salvage chemotherapy (A + SC, n = 19). The ORR, DCR and median PFS for three groups were 6.3% (95%CI 7.1-19.6), 56.3% (95%CI 28.9-83.6), 2.43months, 16.7% (95%CI 26.2-59.5), 66.7% (95%CI 12.5-120.9), 1.13months, 15.8% (95%CI 2.3-33.8), 73.7% (95%CI 51.9-95.5), 2.87months, respectively. There was no significantly difference between three groups in aforementioned response index. The incidence rates of any grade and grade 3-4 adverse events were 80% and 20%, respectively. Bleeding (20%), hand-foot syndrome (13.3%), and diarrhea (13.3%) were the most common adverse events. Grade 3-4 adverse events include hypertension, hand-foot syndrome, diarrhea, anemia, and thrombocytopenia. There was no adverse events-related death. Conclusions: For heavily pretreated pediatric solid tumors, anlotinib may be an effective treatment with tolerable adverse events. Further prospective randomized controlled clinical study is warranted.[Table: see text]

scholarly journals 354 Lenvatinib and pembrolizumab in advanced endometrial carcinoma (EC): long-term efficacy and safety update from a phase 1b/2 study

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A381-A381
Author(s):  
Vicky Makker ◽  
Carol Aghajanian ◽  
Allen Cohn ◽  
Margarita Romeo ◽  
Raquel Bratos ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Center ◽  
Efficacy And Safety ◽  
Open Label ◽  
Phase 3 ◽  
Efficacy Analysis ◽  
Phase 1B ◽  
Grade 3 ◽  
Cutoff Date

BackgroundLenvatinib is a multikinase inhibitor of VEGFR 1–3, FGFR 1–4, PDGFRα, RET, and KIT. Pembrolizumab is an anti-programmed death-1 monoclonal antibody. We previously reported results from a cohort of 108 patients with metastatic EC (data cutoff date, January 10, 2019) who received lenvatinib + pembrolizumab as part of an ongoing multicenter, open-label, phase 1b/2 study evaluating the combination treatment in patients with selected solid tumors (NCT02501096). Lenvatinib + pembrolizumab showed a tolerable safety profile and promising antitumor activity per immune-related (ir) Response Evaluation Criteria In Solid Tumors (RECIST) by investigator assessment, including an objective response rate (ORR) of 38.9% (95% confidence interval [CI], 29.7–48.7), median progression-free survival (PFS) of 7.4 months (95% CI, 5.3–8.7), and median overall survival (OS) of 16.7 months (95% CI, 15.0-not estimable).1 Here we present updated efficacy and safety data (data cutoff date: August 18, 2020).MethodsPatients included in the EC cohort had histologically confirmed, measurable metastatic EC and had received ≤2 prior chemotherapies (unless discussed with the sponsor). Patients received lenvatinib (20 mg orally once daily) and pembrolizumab (200 mg intravenously once every 3 weeks). The phase 2 efficacy endpoints included ORR, PFS, OS, and duration of response. Tumor assessments for primary and secondary endpoints were evaluated by investigators per irRECIST.ResultsThe 108 patients from the key efficacy analysis set for the previously reported results were all included in these updated analyses. Median follow-up duration for the study was 34.7 months. Efficacy outcomes are summarized in table 1. Treatment-related adverse events (TRAEs) occurred in 104 (96%) patients (94 [87%] grade ≤3, 10 [9%] grade ≥4). TRAEs led to study-drug interruption of 1 or both drugs in 80 (74.1%) patients and dose reductions of lenvatinib in 73 (67.6%) patients; 23 (21.3%) patients discontinued 1 or both drugs due to a TRAE. The most common grade ≥3 TRAEs were hypertension (33.3%), lipase increased (9.3%), fatigue (8.3%), and diarrhea (7.4%).Abstract 354 Table 1ConclusionsWith extended follow-up, our updated efficacy analysis continued to show clinical benefit in patients with metastatic EC who received lenvatinib + pembrolizumab. Moreover, the combination had a manageable safety profile that was generally consistent with the established safety profiles of the individual monotherapies. No new safety signals were detected. A phase 3 study of lenvatinib + pembrolizumab versus treatment of physician’s choice in advanced endometrial cancer further supports the lasting clinical benefits observed in our study.2Trial Registration www.clinicaltrials.gov NCT02501096ReferencesMakker V, Taylor MH, Aghajanian C, et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer. J Clin Oncol 2020;38(26):2981–2992.Makker V, Colombo N, Casado Herráez A, et al. A multicenter, open-label, randomized, phase 3 study to compare Ethics ApprovalThis study was approved by the following ethics committees/institutional review boards (IRBs): Oregon Health & Sciences University IRB, IntegReview IRB, Memorial Sloan Kettering Cancer Center IRB, University of Pennsylvania Office of Regulatory Affairs IRB, Dana-Farber Cancer Institute IRB, The University of Chicago Biological Sciences Division IRB, University of Texas MD Anderson Cancer Center IRB, Western IRB, Quorum Review IRB, US Oncology, Inc. IRB, CEIm - Comité de Ética de la Investigación con Medicamentos, Regional Komite for Medisinsk og Helsefagli Forskningsetikk, and REC - Regional Committees for Medical and Health Research Ethics. All participants gave informed consent before taking part in this study.ConsentNo identifying information is contained in this abstract so no permission from participants is considered necessary.

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