Anlotinib in patients with recurrent platinum-resistant or refractory ovarian carcinoma: A prospective, single-arm, single-center, phase II clinical study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6061-6061 ◽  
Author(s):  
Boer Shan ◽  
Wenbin Shen ◽  
Huaying Wang
Keyword(s):  
Ovarian Carcinoma ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Therapeutic Effects ◽  
High Grade ◽  
Platinum Resistant ◽  
Gynecologic Tumor ◽  
Hand Foot Syndrome

6061 Background: Recurrent platinum-resistant or refractory ovarian carcinoma is difficult to treat, and how to improve the treatment effect of these patients is still an urgent problem to solve. Anlotinib is a new multi-target tyrosine kinase inhibitor and its anti-tumor vascular targets include VEGFR, PDGFR and FGFR. Previous researches have shown clinical antitumor activity of anlotinib in various cancers, including the phase I study on gynecologic tumor. This phase II study (ChiCTR2000029654) aims to further evaluate the safety and efficacy of anlotinib in patients with recurrent or refractory ovarian carcinoma. Methods: Patients who have previously received second-line or more chemotherapy, with histopathologically confirmed ovarian high-grade serous gonadal carcinoma (including salpingocarcinoma and peritoneal carcinoma), ECOG 0-2 were considered eligible for enrollment. Anlotinib was administered orally (12 mg qd, d1-14; 21 days per cycle) till disease progression, death or intolerant toxicity. Therapeutic effects are evaluated every 6 weeks. The primary endpoint was objective response rate (ORR) and the secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety and quality of life (QOL). Results: Between 2019 March to 2020 January, 15 patients (female) with FIGO histopathological stage IA(6.7%), IIIA (73.3%), IIIC (6.7%) and IV (13.3%) were enrolled and 14 patients were evaluable with a median age of 59 years (range: 47-69). The mean follow-up period is 3.5 months (95% CI: 2.1-4.8). Therapeutic evaluation showed the incidence of partial response, stable disease and progression disease was 14.3%, 57.1% and 28.6% respectively, yielding the ORR of 14.3% (2/14; 95% CI: 1.8%-42.8%) and the DCR of 71.4% (10/14; 95% CI: 41.9%-91.6%). The median PFS was not reached. Most of the occurring AEs were grade 1, including hypertention (57.1%), fatigue (50.0%), hand-foot syndrome (35.7%), hoarseness (14.3%), diarrhea (7.1%), gum-pain (7.1%), decrease in leukocyte count (6.7%) and urine protein (7.1%). Only cancer pain (7.1%) was grade 2. No high grade AE was observed in these 14 patients. Neither unexpected safety signals nor treatment related death occurred. Conclusions: Anlotinib showed a promising efficacy with a favourable toxicity profile for patients with recurrent platinum-resistant or refractory ovarian carcinoma. And we will report more results ahout anlotinib in the future. Clinical trial information: ChiCTR2000029654.

Anlotinib in patients with recurrent platinum-resistant or refractory ovarian carcinoma: A prospective, single-arm, single-center, phase II clinical study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17524-e17524
Author(s):  
Huaying Wang ◽  
Wenbin Shen ◽  
Boer Shan
Keyword(s):  
Growth Factor ◽  
Ovarian Carcinoma ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Safety Data ◽  
Growth Factor Receptor ◽  
Therapeutic Effects ◽  
Platinum Resistant ◽  
Hand Foot Syndrome

e17524 Background: Anlotinib is a new multi-target tyrosine kinase inhibitor (TKI) and its anti-tumor targets include vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), and c-kit. This phase II study aims to evaluate the safety and efficacy of anlotinib monotherapy in patients with recurrent or refractory ovarian carcinoma. We have previously reported primary results (objective response rate (ORR) 35.7%, 95%CI: 12.8-64.9; and disease control rate (DCR) 85.7%, 95%CI: 57.2-98.2) in 14 patients), and we now present the updated ORR, DCR and safety data in more patients. Methods: Patients who have previously received second-line or more chemotherapy, with histopathologically confirmed ovarian high-grade serous gonadal ovarian carcer (including salpingocarcinoma and peritoneal carcinoma), ECOG 0-2 were considered eligible for enrollment. Anlotinib was administered orally (12 mg qd, d1-14; 21 days per cycle) till disease progression, death or intolerant toxicity. Therapeutic effects are evaluated every 6 weeks. The primary endpoint was ORR and the secondary endpoints included DCR, progression-free survival (PFS), overall survival (OS), safety and quality of life (QoL). Results: Between March 2019 and January 2021, 31 patients (female) with FIGO histopathological stage IC (1, 3.2%), IIC (1, 3.2%), IIIC (23, 74.2%) and IV (6, 19.4%) were enrolled and 24 patients were evaluable with a median age of 59 years (range: 37-73). The median treatment period was 4.96 months (95% CI: 4.50-7.56). Therapeutic evaluation showed the incidence of complete response, partial response, stable disease and progression disease was 4.2%, 25%, 45.8% and 25% respectively, yielding the ORR of 29.2% (7/24; 95% CI: 14.6-57.0) and the DCR of 75.0% (18/24; 95% CI: 53.3-90.2). The median PFS was 6.34 months (95% CI: 3.14-9.54). The median OS was not reached. Most of the occurring adverse events (AEs) were grade 1 and grade 2, and ≥10% grade 1 AEs included hypertention (45.83%), fatigue (29.17%), hand-foot syndrome (33.33%) and hoarseness (12.50%). Grade 2 AEs only included gingival bleeding (4.2%), hand-foot syndrome (4.2%), renal dysfunction (4.2%) and cancer pain (4.2%). No higher grade AEs were observed. Neither unexpected safety signals nor treatment related death occurred. Conclusions: Anlotinib showed a promising efficacy with an acceptable safety profile for patients with recurrent platinum-resistant or refractory ovarian carcinoma. Further evaluation of PFS and OS is ongoing. Clinical trial information: ChiCTR2000029654.

scholarly journals Cabozantinib As Salvage Therapy for Patients With Tyrosine Kinase Inhibitor–Refractory Differentiated Thyroid Cancer: Results of a Multicenter Phase II International Thyroid Oncology Group Trial

2017 ◽  
Vol 35 (29) ◽  
pp. 3315-3321 ◽  
Author(s):  
Maria E. Cabanillas ◽  
Jonas A. de Souza ◽  
Susan Geyer ◽  
Lori J. Wirth ◽  
Michael E. Menefee ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Phase Ii ◽  
Differentiated Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Multikinase Inhibitor

Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib. Patients and Methods Patients with RAI-refractory disease with Response Evaluation Criteria in Solid Tumor (RECIST) measurable disease and evidence of progression on prior VEGFR-targeted therapy were enrolled in this single-arm phase II study. The cabozantinib starting dose was 60 mg/day orally but could be escalated to 80 mg if the patient did not experience a response. Patients underwent tumor assessment according to RECIST v1.1 every 8 weeks. In this study, if at least five of 25 response-evaluable patients had an objective response, cabozantinib would be considered a promising agent in this patient population. Results Twenty-five patients were enrolled. The median age was 64 years, and 64% of patients were men. Twenty-one patients had received only one prior VEGFR-targeted therapy (sorafenib, pazopanib, or cediranib), and four patients had received two such therapies. The most common treatment-related adverse events were fatigue, weight loss, diarrhea, palmar-plantar erythrodysesthesia, and hypertension. One drug-related death was noted. Of the 25 patients, 10 (40%) had a partial response, 13 (52%) had stable disease, and two (8%) had nonevaluable disease. The median progression-free survival and overall survival were 12.7 months and 34.7 months, respectively. Conclusion Cabozantinib demonstrated clinically significant, durable objective response activity in patients with RAI-refractory DTC who experienced disease progression while taking prior VEGFR-targeted therapy.

scholarly journals An Observational Study of the First Experience with Bevacizumab for the Treatment of Patients with Recurrent High-Grade Glioma in Two Belgian University Hospitals

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
M. Huylebrouck ◽  
S. Lv ◽  
J. Duerinck ◽  
A. Van Binst ◽  
I. Salmon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tumor Response ◽  
Metabolic Response ◽  
Objective Response ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
High Grade ◽  
University Hospitals ◽  
Phase Ii Trials ◽  
Antiangiogenic Effect

Background. Bevacizumab (BEV), a humanized immunoglobulin G1 monoclonal antibody that inhibits VEGF has demonstrated activity against recurrent high-grade gliomas (HGG) in phase II clinical trials.Patients and Methods. Data were collected from patients with recurrent HGG who initiated treatment with BEV outside a clinical trial protocol at two Belgian university hospitals.Results. 19 patients (11 M/8 F) were administered a total of 138 cycles of BEV (median 4, range 1–31). Tumor response assessment by MRI was available for 15 patients; 2 complete responses and 3 partial responses for an objective response rate of 26% for the intent to treat population were observed on gadolinium-enhanced T1-weighted images; significant regressions on T2/FLAIR were documented in 10 out of 15 patients (67%). A reduced uptake on PET was documented in 3 out of 4 evaluable patients. The six-month progression-free survival was 21% (95% CI 2.7–39.5). Two patients had an ongoing tumor response and remained free from progression after 12 months of BEV treatment.Conclusions. The activity and tolerability of BEV were comparable to results from previous prospective phase II trials. Reduced uptake on PET suggests a metabolic response in addition to an antiangiogenic effect in some cases with favorable clinical outcome.

Efficacy and safety of weekly paclitaxel in elderly patients with heavily pretreated platinum-resistant ovarian carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17552-e17552
Author(s):  
Rodrigo Sanchez-Bayona ◽  
Pablo Tolosa ◽  
Ana Sanchez de Torre ◽  
Alicia Castelo ◽  
Elsa Bernal-Hertfelder ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Ovarian Carcinoma ◽  
Progression Free Survival ◽  
High Grade ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Serous Ovarian Carcinoma ◽  
Platinum Resistant ◽  
Heavily Pretreated ◽  
Grade 3

e17552 Background: In platinum-resistant ovarian cancer treatment, single-agent paclitaxel can be used alone or in combination with bevacizumab. We aimed to assess the efficacy and safety profile of a weekly paclitaxel (WP) scheme in heavily pretreated platinum-resistant high-grade serous ovarian carcinoma. Methods: We retrospectively analyzed 30 adult patients with platinum-resistant high-grade serous ovarian carcinoma treated with WP at our institution between 2015 and 2020. Patients with platinum-resistant ovarian, fallopian tube or primary carcinoma of the peritoneum who had received at least 3 doses of WP (80 mg/m2) alone or in combination with bevacizumab until disease progression or unacceptable toxicity were included in the analysis. Progression-free survival was assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1. Information about toxicity was gathered from medical reports and lab tests. Kaplan-Meier curves and Log-rank test were performed for survival estimates. Results: In our sample, the median age was 68 years (IQR: 60-75) and the median number of previous lines of systemic treatment was 3 (range 1-5). 40% of patients received WP in combination with bevacizumab. The disease control rate was 60.7% (42.9% partial response and 17.8% stable disease). In the overall analysis, the median progression-free survival (mPFS) was 5.0 months (95% CI: 2.0-7.1 months). The presence of ascites significantly shortened the mPFS compared to patients without it (1.1 vs 5.1 months, p < 0.001). Even though the addition of bevacizumab to WP improved the mPFS, the difference was not statistically significant compared to WP alone (7.1 vs 4.06 months, p=0.30). Peripheral neuropathy was the most common adverse event (78% all grades, 18% grade 3). No grade 3 hematologic toxicity was registered. Treatment was discontinued in 6 patients (20%) – 4 due to peripheral neuropathy and two because of toxicoderma. Conclusions: In our sample, WP was an active and safe regimen in heavily pretreated platinum-resistant ovarian carcinoma. WP was well tolerated in elderly patients. The presence of ascites was associated to a shorter PFS in patients treated with WP compared to ascites-free patients.

Subgroup analysis of rucaparib versus chemotherapy as treatment for BRCA-mutated, advanced, relapsed ovarian carcinoma: Effect of platinum sensitivity in the randomized, phase 3 study ARIEL4.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5517-5517
Author(s):  
Amit M. Oza ◽  
Alla Sergeevna Lisyanskaya ◽  
Alexander A. Fedenko ◽  
Mikhail Dvorkin ◽  
Andreia Cristina de Melo ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Subgroup Analysis ◽  
Brca Mutation ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Platinum Sensitivity ◽  
Platinum Sensitive ◽  
Platinum Resistant ◽  
Heavily Pretreated

5517 Background: In ARIEL4 (NCT02855944), rucaparib significantly improved the primary endpoint of progression-free survival (PFS) vs chemotherapy (CT) in patients with advanced, relapsed ovarian carcinoma (OC) harboring a deleterious BRCA1/2 (BRCA) mutation (median PFS 7.4 [95% CI 7.3–9.1] vs 5.7 [5.5–7.3] months; hazard ratio (HR) 0.64 [95% CI 0.49–0.84]; P=0.001). This prespecified exploratory analysis investigated the effect of platinum sensitivity on the efficacy of rucaparib vs CT in ARIEL4. Methods: Patients were randomized 2:1 to oral rucaparib 600 mg twice daily or CT and stratified based on progression-free interval (≥1 to <6 months = platinum resistant; ≥6 to <12 months = partially platinum sensitive; ≥12 months = fully platinum sensitive). In the CT group, patients with platinum-resistant or partially platinum-sensitive disease received weekly paclitaxel 60–80 mg/m2; patients with fully platinum-sensitive disease received investigator’s choice of platinum-based CT (single-agent carboplatin or cisplatin, or platinum doublet). Patients could crossover from CT to rucaparib following radiologic disease progression. Efficacy endpoints were explored in patients with a confirmed BRCA mutation (patients with a reversion mutation were excluded), based on the randomization strata of platinum sensitivity. Results: The visit cutoff date was September 30, 2020. PFS and objective response rates (ORR) per RECIST v1.1 for rucaparib vs CT across subgroups are presented in the Table. The most common treatment-emergent adverse events in the rucaparib group were anemia/decreased hemoglobin (platinum-resistant patients: rucaparib 47% vs CT 40%; partially platinum-sensitive patients: 63% vs 27%; fully platinum-sensitive patients: 58% vs 20%) and nausea (52% vs 21%; 51% vs 23%; 60% vs 68%). In the intent-to-treat population, 74/116 (64%) patients in the CT group crossed over to receive rucaparib: 39/59 (66%) with platinum-resistant, 25/31 (81%) with partially platinum-sensitive, and 10/26 (38%) with fully platinum-sensitive disease. Conclusions: Results from this exploratory subgroup analysis suggest that rucaparib is a reasonable treatment option for heavily pretreated patients across all platinum sensitivity subgroups. Safety was consistent with prior rucaparib studies. Clinical trial information: NCT02855944. [Table: see text]

A phase II study of sunitinib administered in a continuous daily regimen in patients with cytokine-refractory metastatic renal cell carcinoma (mRCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4529-4529 ◽  
Author(s):  
P. H. De Mulder ◽  
J. Roigas ◽  
S. Gillessen ◽  
S. Srinivas ◽  
P. Pisa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
Colon Perforation ◽  
Efficacy Data ◽  
Significant Difference ◽  
Hand Foot Syndrome

4529 Background: Renal cell carcinomas are known for their vascularity and production of high levels of VEGF. Sunitinib malate (SU11248), an oral, multitargeted tyrosine kinase inhibitor of multiple receptors including VEGFR, PDGFR, KIT, RET, and FLT3, has previously demonstrated significant efficacy in 168 patients (pts) with mRCC, with a 42% objective response rate (ORR) at 50 mg/day in 6-week (wk) cycles of 4 wks on treatment followed by 2 wks off. This study sought to determine the efficacy and safety of single-agent sunitinib in mRCC when administered in a continuous 37.5 mg/day regimen. Methods: Pts with histologically proven mRCC, refractory to a cytokine-based regimen, were enrolled in this open-label, multicenter, phase II study. Eligibility criteria included measurable disease, ECOG PS 0/1, and adequate organ function. Pts were randomized to receive sunitinib in the morning (AM) or in the evening (PM) at a dose of 37.5 mg/day, with individual doses subsequently titrated based on tolerability. The primary endpoint was RECIST-defined ORR. Secondary endpoints includedprogression-free survival, adverse events (AEs) and quality of life measures. Results: A total of 88/100 planned pts have been randomized to date: AM (43) and PM (45), and enrollment will be completed by end January 2006. 44 pts have been on continuous sunitinib treatment at 37.5 mg/day for >16 wks (3), >12 wks (9), >8 wks (12), and >4 wks (20). 2 pts (2.3%) discontinued (colon perforation and renal insufficiency) and 9 (10.2%) dose reduced to 25 mg/day due to grade 2/3 AEs: mucositis (2), hand-foot syndrome (2), thrombocytopenia (2), asthenia (1), nausea/diarrhea (1), and neutropenia (1). Preliminary efficacy data show some tumor shrinkage in the majority of patients evaluated at 4 wks, with 3 initial partial responses. There has been no significant difference between pts who received AM or PM doses. The most commonly reported AEs were mucositis, fatigue, hair/skin discoloration, and hand-foot syndrome. Conclusions: Sunitinib administered at a continuous dose of 37.5 mg/day was generally well tolerated; only a few patients required treatment breaks and/or dose reduction. Preliminary efficacy data are encouraging. Mature data will be presented. [Table: see text]

Imatinib mesylate in the treatment of patients with recurrent high grade gliomas expressing PDGF-R

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1526-1526 ◽  
Author(s):  
C. Marosi ◽  
M. Vedadinejad ◽  
C. Haberler ◽  
J. A. Hainfellner ◽  
K. Dieckmann ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Tumor Tissue ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
High Grade ◽  
Best Response ◽  
Major Response ◽  
High Grade Gliomas ◽  
Patients Experience

1526 Background: Despite noticeable progress in the treatment of high-grade gliomas (HGG), most patients experience tumor recurrence after standard treatment consisting of surgery, radiotherapy and concomitant chemotherapy. Imatinib mesylate, a tyrosine kinase inhibitor of PDGFR-α, -β, c-kit, abl and arg, has been shown to produce tumor response in patients with recurrent gliomas (Raymond ProcASCO 2004, Dresemann ProcASCO 2004&2005, Reardon Proc ASCO 2005). We treated 34 patients with recurrent HGGs showing immunohistochemical expression of “imatinib targets” in the tumor tissue with imatinib. Methods: 34 patients, 16 women, 18 men, aged from 27 to 72 years, in median 49 years with recurrent HGG (GBM n= 23, AA n=11) were treated with imatinib 400 mg/day as continuous daily oral dosing. MRI was performed every three months or at clinical suspicion of progression. The median interval from diagnosis to the start of imatinib was 12.6 months (range 4.3 to 143 months). Imatinib was the 2nd line therapy in 15 patients, 3rd line in 13 and 4th line in 6 patients. ECOG performance score at start of imatinib was 1 in 9, 2 in 21 and 3 in 4 patients, respectively.Immunohistochemical analysis was performed on formalin fixed and paraffin embedded tumor tissue with antibodies against PDGFR-α, and -β. Results: The median treatment period with imatinib was 4 months (3 weeks to 17 months). The best response achieved was major response in 2 patients, partial remission in 6, stable disease in 12 and progressive disease in 14 patients. Eleven patients were free from tumor progression after 6 months (PFS-6 32,4%). The two patients with major response improved clinically and showed no more evidence of increased metabolism as well in MRI spectroscopy as in C11-methionine PET for 13 and 17 months, respectively. One of them showed widespread PDGF-R-α expression in the tumor tissue. In all patients with objective response to imatinib, a clinical benefit was noted within the first month of treatment. Conclusions: Compared to the results of Raymond et al, we observed a higher percentage of patients with progression free survival at 6 months. Detailed analysis of imatinib targets in tumor tissue of patients treated with imatinib will be helpful to explore the potential of imatinib as treatment option for patients with HGG. No significant financial relationships to disclose.

A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5576-5576
Author(s):  
S. Welch ◽  
H. J. Mackay ◽  
H. Hirte ◽  
G. F. Fleming ◽  
R. Morgan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Second Stage ◽  
Best Response ◽  
Grade 3 ◽  
Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

Phase II study of cabozantinib (cabo) in patients (pts) with recurrent/metastatic endometrial cancer (EC): A study of the Princess Margaret, Chicago, and California phase II consortia.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5524-5524 ◽  
Author(s):  
Neesha C. Dhani ◽  
Hal W. Hirte ◽  
Julia V. Burnier ◽  
Angela Jain ◽  
Marcus O. Butler ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Mutational Analysis ◽  
Single Agent ◽  
Progression Free Survival ◽  
Current Data ◽  
Pik3ca Mutations ◽  
Primary Endpoints ◽  
Hand Foot Syndrome ◽  
Grade 3

5524 Background: Recurrent/metastatic EC has a poor prognosis with no standard 2ndline therapy. Cabo is a multi-targeted kinase inhibitor of MET, VEGFR, TIE2, AXL & KIT, relevant in epithelial-stromal cross-talk. The role of MET/HGF in aggressive EC biology, where transient benefit of VEGF-targeting is due to MET/HGF, TIE2 & AXL, provides rationale for MET targeting in EC. Methods: PHL86 (NCI#9322/NCT01935934) is a multi-centre, phase II trial of cabo (60mg oral daily dose) in pts with EC recurring within a year of adjuvant chemotherapy (ctx), or with progression after 1 line of ctx for metastatic disease. Experimental (E) cohort was stratified by histology (serous (SER) vs endometroid (END)) in a Simon two-stage design for co-primary endpoints of response rate ( > 30%) & 12-week progression-free-survival (PFS) ( > 55%). Activity was defined as > 7 partial responses (PRs) or > 15 instances of 12 wk-PFS in 36 pts. Pts with rare histology EC were treated in a parallel exploratory (Ex) cohort. Results: From May 2013 to Nov 2016, 102 pts (E: 71; Ex: 31) have been treated with cabo after prior radiation (59) and/or ctx (no. lines: 1(77); 2(22)). Cabo was well tolerated with common toxicities of fatigue, nausea, diarrhea & hand-foot syndrome. Most frequent Grade 3/4 toxicity was hypertension (32/101 pts). Fistula/perforation occurred in 4 of 71 SER/END pts & 4 of 31 Ex pts; no risk factors were identified. In 33 END pts, 6 PRs & 24 instances of > 12-wk PFS were observed; median PFS is 4.8 mths (95% CI: 4.4 – 6.4) with estimated 6-mth PFS of 43% (95% CI: 27 to 59%). In 34 SER pts, 4 PRs & 20 instances of > 12-wk PFS were observed; median PFS is 4.0 mths (95% CI: 2.7 – 4.7) with estimated 6-mth PFS of 30% (95% CI: 15 to 46%). 4 pts have had PFS > 12 mths, 1 SER pt remains on study after 25mths. Mutational analysis demonstrated presence of KRAS with PTEN or PIK3CA mutations in 9 (SER/END) pts, of whom 8/9 pts met 12-wk PFS endpoint, with a median PFS 5.9 mth (4.1 to 15.4). Conclusions: Cabo has single agent activity in END and SER EC with durable disease control. Concurrent mutation in KRAS/PTEN/PIK3CA may enrich for response. The current data support further evaluation of cabo in EC. Clinical trial information: NCT01935934.

Phase II study of apatinib combined with temozolomide in advanced melanoma patients after failure of anti-PD-1 therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22043-e22043
Author(s):  
Li Zhou ◽  
Chuanliang Cui ◽  
Lu Si ◽  
Zhihong Chi ◽  
Xinan Sheng ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Lactate Dehydrogenase Level ◽  
Advanced Melanoma ◽  
First Line Therapy ◽  
Hand Foot Syndrome ◽  
Melanoma Patients

e22043 Background: Immunotherapy is first-line therapy in advanced melanoma. Because of different subtypes and gene alterations, the efficacy of immunotherapy in Asians, mostly comprised of acral and mucosal melanoma, is lower than Caucasians. There are no standard treatment strategies after immunotherapy failure. Chemotherapy and anti-angiogenesis combination showed emerging evidence of activity in mucosal and acral melanoma. This study was to evaluate the efficacy of apatinib combined with temozolomide in advanced immunotherapy refractory melanoma patients (pts). Methods: This prospective, single-arm, phase II study recruited unresectable or metastatic melanoma pts after failure of anti-PD-1 therapy. Other treatment including targeted therapy, chemotherapy, and clinical trials were allowed. Primary endpoint was progression-free survival (PFS), and secondary endpoints were objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). According to the dose recommended from previous phase I study, pts were given apatinib 500 mg every day and temozolomide 300mg day 1-5, 28 days for one cycle. Results: 31 pts were enrolled between Feb 2018 and Dec 2018, with 8 males, average age 55 yrs (range 24 – 69 yrs). 13 pts (41.9%) were from mucosal primaries, 9 (29.0%) acral, 5 (16.1%) cutaneous (non-acral), and 4 (12.9%) unknown primaries. One had BRAF mutation, 1 CKIT, and 3 NRAS mutations. 9 pts (29.0%) were classified as IIIc/M1a, 9 (29.0%) M1b, and 13 (41.9%) M1c. 18 pts (58.1%) had elevated lactate dehydrogenase level. All pts progressed after anti-PD-1 therapy. In addition, 29.0% pts received dacarbazine based chemotherapy, 29.0% paclitaxel or albumin-bound paclitaxel, and 3.2% had dabrafenib with trametinib. Up to Dec 2019, 30 pts can be evaluated for efficacy. Median follow-up time was 10.2 mos (2.0-23.1 mos). There were 5 confirmed PRs and 20 SDs. ORR was 16.7%, DCR 83.3%, and median PFS was 5.0 mos (95%CI 1.9-8.1 mos). Median overall survival was 10.1 mos (95%CI 4.7-15.5 mos). Common AEs were hypertension (51.6%), proteinuria (41.9%), elevated transaminase (25.8%), thrombocytopenia (16.1%), and hand-foot syndrome (16.1%). Most were grade 1-2. Grade 3-4 AEs included proteinuria (12.9%), hypertension (6.4%), and thrombocytopenia (6.4%); 10 pts required a dose reduction, and 1 had to discontinue. No treatment-related deaths were observed. Conclusions: In pts progressed after anti-PD-1 therapy, apatinib in combination with temozolomide demonstrated promising efficacy and favorable safety profile. Clinical trial information: NCT03422445.

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