SWOG 0514: A phase II study of sorafenib (BAY 43–9006) as single agent in patients (pts) with unresectable or metastatic gallbladder cancer or cholangiocarcinomas

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4639-4639 ◽  
Author(s):  
A. B. El-Khoueiry ◽  
C. Rankin ◽  
H. J. Lenz ◽  
P. Philip ◽  
S. E. Rivkin ◽  
...  
Keyword(s):  
Median Survival ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Objective Response ◽  
Response Probability ◽  
Progression Free Survival ◽  
Reversible Posterior Leukoencephalopathy Syndrome ◽  
Posterior Leukoencephalopathy ◽  
Days Of Therapy ◽  
Hand Foot Syndrome

4639 Background: There are no standard chemotherapeutic regimens for incurable biliary adenocarcinomas. Gemcitabine and fluoropyrimidine- based chemotherapy results in occasional responses and a median survival approaching 6 months. Given the presence of b- raf mutations and overexpression of VEGF in biliary cancers, we initiated a study to evaluate the efficacy of sorafenib, a multitargeted tyrosine kinase inhibitor of c and b-Raf, VEGFR-2/3 and PDGFR, in pts with metastatic biliary cancers. Methods: Pt eligibility included adequate organ function and no prior treatment for metastatic disease. The primary end-point was objective response rate (RR). Secondary endpoints were overall survival (OS) and progression free survival (PFS). A two-stage design was used to detect a difference in the null hypothesis of 5% response probability and the alternative 20% response probability. If at least one confirmed response occurred after the first 25 pts, another 25 were to be accrued. Sorafenib was administered at 400 mg PO BID continuously. A cycle was defined as 28 days of therapy, and radiological assessment was done every 2 cycles. Results: 36 pts were enrolled during the first stage of accrual. 5 pts were ineligible. 52% were female. Median age was 57.8 years (range 33.8–81.5). Adverse events: 1 pt died with grade 4 supraventricular tachycardia and venous thromboembolism. Grade 3/4 toxicities were noted in 20 pts (66.7%) and included hand-foot syndrome in 4 pts (13%), while thrombosis/embolism, elevated liver transaminases, and abdominal pain were each seen in 3 pts (10% for each). Reversible posterior leukoencephalopathy syndrome, GI perforation, and GI hemorrhage were each seen in 1 pt (3% for each). 2 pts (6%) had an unconfirmed partial response and 9 pts (29%) had stable disease. 27 pts have progressed. Median PFS was 2 months (95% CI: 2–4 months). 14 pts have died, with a median survival estimate of 6 months (95% CI: 4–10 months). Conclusions: Sorafenib did not result in a clinically significant objective RR in pts with gallbladder and cholangiocarcinoma but demonstrated an impact on survival that may be comparable to commonly used chemotherapy regimens. No significant financial relationships to disclose.

Continuous daily administration of sunitinib in patients (pts) with cytokine-refractory metastatic renal cell carcinoma (mRCC): Updated results

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5040-5040 ◽  
Author(s):  
S. Srinivas ◽  
J. Roigas ◽  
S. Gillessen ◽  
U. Harmenberg ◽  
P. H. De Mulder ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Eligibility Criteria ◽  
Best Response ◽  
Hand Foot Syndrome

5040 Background: Sunitinib malate, an oral, multitargeted tyrosine kinase inhibitor of multiple receptors, showed significant efficacy in 168 pts with cytokine refractory mRCC, with a 42% objective response rate (ORR) and progression-free survival (PFS) of 8.2 months at 50 mg/day (4 weeks on treatment, 2 weeks off) per investigator assessment (Motzer et al. JAMA 2006;295:2516–24). This study was designed to determine the efficacy and safety of single-agent sunitinib 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 included PFS, adverse events (AEs) and quality of life measures. Results: 107 pts were randomized to AM (54) or PM (53) dosing and have been on study a median of 6.8 months (0.4 to 13.3). As of October 2006, 55 pts have discontinued due to progression (37 pts [35%]), AEs (17 pts [16%]), and 1 consent withdrawal (1%); 47 pts (44%) were dose reduced to 25 mg/day due to grade 2/3 AEs, the most frequent being: asthenia (12%), hand-foot syndrome (8%), and diarrhea (5%). The most commonly reported (=5% of pts) grade 3/4 AEs were hypertension (10%), asthenia (9%), hand-foot syndrome (9%), anorexia (8%), and diarrhea (6%). 31 pts (29%) were maintained on continuous sunitinib at 37.5 mg/day, and 29 (27%) were escalated to 50 mg/day. There were no significant differences between pts who received AM or PM dosing. Quality of life results will be presented. The best response by RECIST per investigator assessment shows an ORR of 19% with 43 pts (40%) with =6 months of stable disease. The median PFS is 8.3 months. Conclusions: Sunitinib 37.5 mg/day continuous dosing has a manageable safety profile and demonstrates promising clinical benefit as second-line therapy in mRCC. This regimen provides alternative sunitinib dosing that can be explored in combination studies. No significant financial relationships to disclose.

Response to selpercatinib versus prior systemic therapy in patients (pts) with RET fusion+ non-small-cell lung cancer (NSCLC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9032-9032
Author(s):  
Alexander E. Drilon ◽  
Oliver Gautschi ◽  
Benjamin Besse ◽  
Vivek Subbiah ◽  
Daniel Shao-Weng Tan ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Kinase Inhibitor ◽  
Phase 1 ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Survival Duration ◽  
Prior Therapy ◽  
Platinum Based Chemotherapy ◽  
Systemic Therapies

9032 Background: Selpercatinib, a first-in-class highly selective, potent, CNS-active RET kinase inhibitor, is approved in multiple countries for treatment of RET fusion+ lung or thyroid cancers. Selpercatinib demonstrated durable antitumor activity in previously treated pts with RET fusion+ NSCLC in an ongoing Phase 1/2 trial, LIBRETTO-001 (Besse et al., ASCO 2021). Methods: Pts with RET fusion+ NSCLC enrolled in the global, multicenter, LIBRETTO-001 trial (NCT03157128; 16 countries, 89 sites). Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival, duration of response, and safety. This post-hoc intrapatient analysis was based on a 30 March 2020 data cutoff date. Historical physician-reported best overall response (BOR) from last systemic therapy received prior to enrollment was compared with selpercatinib BOR by independent review committee per RECIST v1.1, with each patient serving as his/her own control. Results: In efficacy-evaluable pts (N = 218) who previously received platinum-based chemotherapy (chemo), median pt age was 61 years, the majority with ECOG of 0/1 (37%/61%), with a median of 2 (range: 1-15) prior systemic therapies. Overall, 57% of patients responded to selpercatinib while 16% responded to the immediate prior therapy. ORR improvements with selpercatinib were observed regardless of prior therapy: chemotherapy + immune checkpoint inhibitor (ICI) (57% vs 14%), single-agent ICI (48% vs 3%), or chemotherapy (58% vs 15%). A total of 108 patients (49%) did not respond to immediate prior therapy but responded to selpercatinib. Fewer patients had progressive disease as their BOR with selpercatinib (2%) compared to the immediate prior therapy (28%). The median duration of therapy for selpercatinib was notably extended compared with that of the immediate prior therapy (11.8 vs. 3.4 months, respectively). Conclusions: In pts with RET fusion+ NSCLC treated on LIBRETTO-001, systemic therapies administered prior to enrollment achieved less meaningful clinical benefit than selpercatinib. Selpercatinib demonstrated consistent efficacy regardless of the type of prior therapy. Clinical trial information: NCT03157128.

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]

S0413: A phase II SWOG study of GW572016 (lapatinib) as first line therapy in patients (pts) with advanced or metastatic gastric cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4621-4621 ◽  
Author(s):  
S. Iqbal ◽  
B. Goldman ◽  
H. J. Lenz ◽  
C. M. Fenoglio-Preiser ◽  
C. D. Blanke
Keyword(s):  
Gastric Cancer ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Response Probability ◽  
Metastatic Gastric Cancer ◽  
Clinical Analysis ◽  
Primary Objective ◽  
First Line Therapy ◽  
Days Of Therapy ◽  
Gastric Cancer Patients

4621 Background: GW572016 is a dual tyrosine kinase inhibitor of EGFR and HER2/ErbB2. Overexpression of EGFR and ErbB2 has been described in 15 to 45% of gastric cancer, making this a potential target in advanced/metastatic tumors. Methods: The primary objective of this study was to assess the response rate (confirmed complete (CR) and partial responses (PR)). Secondary objectives included time to treatment failure (TTF), overall survival (OS), toxicities and the relationship of EGFR, ErbB2, and markers of angiogenesis with clinical outcome in patients treated with GW572016. A two-stage design was used to detect a difference in the null hypothesis of 5% response probability and the alternative 20% response probability. If at least one response occurred after the first 20 pts, another 20 were to be accrued. GW572016 was administered to chemonaiive metastatic gastric cancer patients at a dose of 1,500 mg orally daily. A cycle was defined as 28 days of therapy, and patients were staged after 2 cycles of treatment. Results: The study met its first stage goal, and continued until full accrual. The study accrued 47 pts from February 2005 until May 2006. Two patients lacked required tissue/blood submission but are included in this clinical analysis. One patient did not receive treatment and is not analyzable. Pt characteristics: male/female30/16 (65%/35%); median age 68.7 years (range 38.9 - 90). Significant toxicities: 1 grade 4 cardiac ischemia/infarction, 2 grade 4 fatigue, 1 grade 4 vomiting. There was one treatment related death due to CNS ischemia. Three pts (7%) had a confirmed PR and 2 (5%) unconfirmed PR, and 9 (20%) had stable disease. Median TTF was 2 months, and OS was 5 months. Molecular correlative data was available on 42 pts. Conclusions: GW572016 is a well tolerated regimen with modest single-agent activity in pts with advanced/metastatic gastric cancer. Although, GW572016 did not meet the primary endpoint, this targeted agent may warrant further investigation in combination regimens. Molecular correlatives will be reported in a separate abstract. No significant financial relationships to disclose.

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.

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.

Sunitinib (SU) in combination with docetaxel (D) versus D alone for the first-line treatment of advanced breast cancer (ABC).

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA1010-LBA1010 ◽  
Author(s):  
J. Bergh ◽  
R. Greil ◽  
N. Voytko ◽  
A. Makhson ◽  
J. Cortes ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Objective Response ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Open Label ◽  
Recommended Treatment

LBA1010 Background: Taxane-based chemotherapy (CT) improves progression-free survival (PFS) in patients (pts) with newly diagnosed HER2-negative metastatic BC (MBC). SU, an oral multitargeted tyrosine kinase inhibitor (MTKI), demonstrated antitumor activity in combination with D in a phase I/II study in pts with MBC. A randomized, open-label, multicenter phase III trial in pts with newly diagnosed ABC tested the hypothesis that addition of a MTKI to D improves PFS vs. D alone. Methods: Eligible pts (female; ≥18 yrs) had an ECOG PS ≤1, and newly diagnosed HER2-negative MBC or ABC. If (neo)adjuvant therapy included a taxane, relapse must have occurred ≥12 mos after CT. Pts were randomized (1:1) to treatment (tx) with D 75 mg/m2 iv on day 1 and SU 37.5 mg/day po from day 2–15 q3w (Schedule 2/1; Arm A), or to D 100 mg/m2 iv 1-hr infusion q3w (Arm B) that could be given until progression. If D was discontinued in Arm A for reasons other than progressive disease (PD), single-agent SU 37.5 mg daily was permitted until PD. Median, independently assessed, PFS (primary endpoint) was compared between tx arms using stratified and unstratified log-rank tests. Overall objective response rate (ORR), overall survival (OS), pt-reported outcomes, and safety were secondary endpoints. Results: As of the data cutoff (February 1, 2010), the ITT population comprised 593 pts (SU+D, n=296; D, n=297). The trial did not meet its primary endpoint of prolonging PFS based on the independent radiologic assessment or in prolonging OS. Baseline characteristics were well balanced. Median relative dose intensity (RDI) was 94.2% and 92.4% for SU+D, and 92.6% for D arms, respectively. Median PFS was 8.6 mos (95% CI 8.2–10.3) in the SU+D arm vs 8.3 mos (95% CI 7.7–9.6) for the D arm (HR 0.922). Median OS was 24.8 mos (95% CI 21.5–33.1) in SU+D arm vs 25.5 mos (95% CI 22.8–27.8) for D arm (HR 1.207). ORR was significantly better for SU+D (51%) vs. D (39%) (p=0.0018). Frequent all causality grade 3/4 adverse events (≥10%) were neutropenia (46%), hand–foot syndrome (17%), and fatigue (12%) in the SU+D arm and neutropenia (44%) in the D arm. Conclusions: Based on these data, SU+D is not a recommended treatment option for patients with newly diagnosed ABC. Strategies using antiangiogenic TKIs that increase RR but not OS may need to be revisited. [Table: see text]

scholarly journals An Oral Small Molecule VEGFR2 Inhibitor, Apatinib, in Patients with Recurrent or Refractory Cervical Cancer: A Real World Study

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Ning Li ◽  
Ziyi Wang ◽  
Guangwen Yuan ◽  
Yangchun Sun ◽  
Rong Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Cancer Center ◽  
Cancer Hospital ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Antiangiogenic Drug

To evaluate the efficacy and safety of apatinib, an oral antiangiogenic drug, in patients with recurrent or refractory cervical cancer as salvage treatment, we retrospectively analyzed the medical records of recurrent or refractory cervical cancer patients admitted to the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Hunan Cancer Hospital, from October 1, 2016, to December 31, 2017. Patients who progressed within 6 months after the last treatment were given apatinib orally at a dose of 250 mg daily until disease progression or unacceptable toxicity. Twenty-nine patients were enrolled in our retrospective study. Up to February 1, 2019, the median follow-up time was 18 months. The median progression-free survival was 128 days (95% confidence interval (CI): 20–540 days), and the median overall survival was 9 months (95% CI: 4–23 months). The longest period of apatinib administration was 540 days. No complete response was observed, 5 (17.2%) patients achieved partial response, and 11 (37.9%) achieved stable disease. The objective response rate and disease control rate were 17.2% and 55.1%, respectively. The most common adverse events were hypertension (G1, 65.5%, 19/29), mucositis (G1, 55.2%, 16/29), hand-foot syndrome (G1-2, 44.8%, 13/29), and proteinuria (G1-2, 20.7%, 6/29). Grade 3 proteinuria occurred in only one patient (3.4%, 1/29). Apatinib single-agent use might be an effective and tolerable choice as salvage therapy for patients with recurrent or refractory cervical cancer.

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 Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma

2021 ◽  
Vol 9 (6) ◽  
pp. e002057
Author(s):  
Yousef Zakharia ◽  
Robert R McWilliams ◽  
Olivier Rixe ◽  
Joseph Drabick ◽  
Montaser F Shaheen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Advanced Melanoma ◽  
Free Survival ◽  
Programmed Death ◽  
Evaluable Population

BackgroundThe indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma.MethodsPatients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label.ResultsBetween July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator’s choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P).ConclusionIn this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.

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