Anlotinib plus pemetrexed as a further treatment for patients with platinum-resistant ovarian cancer: A single-arm, open-label, phase II study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5533-5533
Author(s):  
Jueming Chen ◽  
Wei Wei ◽  
Lie Zheng ◽  
Han Li ◽  
Yanling Feng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Kinase Inhibitor ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Open Label ◽  
Platinum Resistant ◽  
Grade 3

5533 Background: Non-platinum chemotherapy is widely used in platinum-resistant recurrent ovarian cancer treatment but with limited efficacy. Combing chemotherapy with angiogenic inhibitors is a new therapeutic choice. Anlotinib is a novel tyrosine kinase inhibitor targeting multiple receptors involved in tumor proliferation, vasculature, and tumor microenvironment. The study aimed to further assess the efficacy and safety of anlotinib combined with pemetrexed in platinum-resistant ovarian cancer. Methods: Patients who had received at least two different chemotherapy regimens (including the first line platinum-based regimen), with histologically proven recurrent platinum-resistant or platinum-refractory epithelial ovarian cancer (including salpingocarcinoma and peritoneal carcinoma), ECOG 0-2, were considered eligible for enrollment to receive six 21-days cycles of anlotinib (12 mg QD from day 1 to 14; 21 days per cycle) orally plus pemetrexed intravenously (0.5 g/m2 on day 1; 21 days per cycle). Subsequent maintenance treatment was anlotinib monotherapy (12 mg QD from day 1 to 14; 21 days per cycle) till disease progression or intolerant toxicity. The primary endpoint was objective response rate (ORR), and the secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and safety. Results: As of Jan 2021, 27 patients were enrolled. The median number of chemotherapy was 4 (range, 2-10) and 51.9% (14/27) of patients had ever received antiangiogenic therapy. The ORR was 36.4% (partial response (PR) in 8 patients; 95% CI, 17.2-59.3). The DCR was 100.0% (PR in 8 patients and stable disease (SD) in 14 patients; 95% CI, 73.5-100). The median time of the first response was 1.6 months (range, 1.3-4.4). The median PFS was 9.3 months (95% CI, NE-NE). Furthermore, the ORR of patients with and without prior antiangiogenic therapy was 16.7% (95%CI, 2.1-48.4) and 60.0% (95%CI, 26.2-87.8) respectively (P = 0.074). Any grades of adverse events (AEs) were observed in 92.6% (25/27) of patients, containing allergic eruption (33.3%), hand-foot syndrome (29.6%), hypertension (25.9%), and fatigue (25.9%). The grade 3-4 adverse events were only observed in 5 patients, including 1 with grade 3 proteinuria, 1 with grade 3 ascites, 1 with grade 3 fatigue, 1 with grade 3 edema limbs and 1 with grade 4 anemia. Conclusions: The treatment of anlotinib plus pemetrexed showed a promising antitumor activity with tolerable toxicity for patients in platinum-resistant and refractory ovarian cancer. Clinical trial information: ChiCTR2000029654.

Preliminary results of anlotinib and niraparib dual therapy evaluation in platinum-resistant recurrent ovarian cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17532-e17532
Author(s):  
Guochen Liu ◽  
Jihong Liu ◽  
Bingna Xian ◽  
Jing Li ◽  
Yanling Feng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Skin Reaction ◽  
Group Performance ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Recurrent Ovarian Cancer ◽  
Platinum Resistant ◽  
Hand Foot Skin Reaction

e17532 Background: Patients with platinum-resistant ovarian cancer have a poor prognosis. Effective treatment options for these patients are limited. Combination of PARP inhibitors and antiangiogenic therapy is reported as an effective antitumor strategy. In this study (ANNIE), we evaluate the activity of niraparib combined with anlotinib in patients with platinum resistant recurrent ovarian carcinoma. Methods: The ANNIE trial (ClinicalTrials.gov identifier NCT04376073) was a multicentre, single-arm, phase 2 study that evaluated the safety and activity of niraparib combined with anlotinib in patients (≥18 & ≤70 years, an Eastern Cooperative Oncology Group performance status of 0 or 1) with recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer cancer whose disease recurred in less than 6 months after the last administered platinum therapy, and with measurable disease according to the Response Evaluation Criteria in Solid Tumors. Patients received oral niraparib 300mg/200mg once daily continuously and anlotinib 12mg (The initial dose was reduced to 10mg on November 1, 2020) on day 1-14 of each 21-day cycle thereafter until disease progression or intolerable toxicity. The primary objective was to assess objective response rate (ORR; complete plus partial responses) according to RECIST version 1.1. 40 cases are planned to be enrolled. Results: Between May 22, 2020 and February 6, 2021, we enrolled 33 patients (median age, 56 years [range, 37-69 years]). Patients had received a median of six (range, 2-9) previous lines of therapy. The cut-off date of analysis was February 4, 2021, the median follow-up was 4.1 months (range, 0.1–8.1). At data cutoff, all but seven (2 voluntarily withdrew, 5 with progressive disease) of the patients were still on treatment. Twenty-five patients underwent imaging evaluation. The confirmed best overall response assessment showed 12 with partial responses, 12 with stable disease, yielding the ORR of 48.0% (95% CI, 27.0%̃69.0%). The median duration of response and the median PFS were not reached. Drug-related grade 3 or worse treatment-emergent adverse events were occurred in 39.4% patients, including hand-foot skin reaction (3 pts), thrombocytopenia (2 pts), hypertriglyceridemia (2 pts), neutropenia (2 pts), anemia (1 pts) and hypertension (1 pts). The most common treatment emergent adverse events were hand-foot skin reaction (36.4%), hypertension (36.4%), and thrombocytopenia (33.3%). No treatment-related death was recorded. Enrollment was ongoing so far. Conclusions: Niraparib in combination with anlotinib showed promising antitumor activity and tolerable toxicity in patients with platinum resistant recurrent ovarian cancer. The conclusion can be clarified after the research is completed. Clinical trial information: NCT04376073.

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]

A randomized phase 2 trial comparing efficacy of the combination of the PARP inhibitor olaparib and the antiangiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer.

2014 ◽  
Vol 32 (18_suppl) ◽  
pp. LBA5500-LBA5500 ◽  
Author(s):  
Joyce Liu ◽  
William Thomas Barry ◽  
Michael J. Birrer ◽  
Jung-min Lee ◽  
Ronald J. Buckanovich ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase 1 ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Parp Inhibitors ◽  
Open Label ◽  
Angiogenic Therapy ◽  
Platinum Sensitive

LBA5500 Background: PARP inhibitors and anti-angiogenics are clinically active in recurrent ovarian cancer (OvCa). Preclinical studies suggest these agents can synergize, and a phase 1 study showed that the combination of cediranib (ced) and olaparib (olap) is well-tolerated. We therefore compared the activity of olap alone (Olap) to combined ced and olap (Ced/Olap) in treatment of recurrent platinum-sensitive (plat-sens) high-grade serous (HGS) or BRCA-related OvCa (NCT 01116648). Methods: Patients (pts) across 9 centers were randomized 1:1 in this Ph 2 open label study to Olap (olap 400 mg capsules BID) or Ced/Olap (olap 200 mg capsules BID; ced 30 mg daily), stratified by BRCA status and prior anti-angiogenic therapy. Eligibility included pts with recurrent plat-sens HGS or BRCA-related OvCa. Pts had measurable disease by RECIST 1.1, PS 0 or 1, and the ability to take POs. No prior anti-angiogenics in the recurrent setting or prior PARP inhibitor was allowed. Progression-free survival (PFS) was defined as time from randomization to radiographic progression or death. With a target N=90 pts, the study was powered to detect a hazard ratio (HR) of 1.75 (median PFS 6 vs 10.5 mo). Results: Pts were enrolled from Oct 2011 to Jun 2013: 46 to Olap, 44 to Ced/Olap. 48 pts were known BRCA carriers (25 Olap; 23 Ced/Olap). At a planned interim analysis the DSMB recommended release of data. As of Jan 7, 2014, 41 pts had a PFS event. Median PFS was 9.0 mos for Olap and 17.7 mos for Ced/Olap (HR 2.9, 95% CI 1.5-5.6, p = 0.001). There were 2 complete responses (CR) and 21 partial responses (PR) in pts on Olap (56% objective response rate, ORR) and 3 CRs and 33 PRs in pts on Ced/Olap (84% ORR, p = 0.008). The overall rate of Gr3/4 toxicity was higher for pts on Ced/Olap (70%) than on Olap (7%). Differentially occurring toxicities included fatigue (27% Ced/Olap vs 7% Olap), diarrhea (23% vs 0%), and hypertension (39% vs 0%). Updated efficacy and exploratory subgroup analyses will be presented. Conclusions: Combined Ced/Olap significantly extended PFS and ORR compared to Olap in plat-sens OvCa. Further studies of this oral combination in plat-sens OvCa are warranted. Clinical trial information: NCT01116648.

SAVOIR: A phase III study of savolitinib versus sunitinib in pts with MET-driven papillary renal cell carcinoma (PRCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5002-5002
Author(s):  
Toni K. Choueiri ◽  
Daniel Yick Chin Heng ◽  
Jae-Lyun Lee ◽  
Mathilde Cancel ◽  
Remy B Verheijen ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Randomized Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Chromosome 7 ◽  
Phase Iii ◽  
Open Label ◽  
Grade 3 ◽  
Dose Modifications

5002 Background: PRCC is the most common type of non-clear cell RCC, accounting for 10–15% of renal malignancies. As a subset of PRCC cases are MET-driven, MET inhibition may be an appropriate targeted treatment approach. In a single-arm Phase II study, savolitinib (AZD6094, HMPL‐504, volitinib), a highly selective MET-tyrosine kinase inhibitor, demonstrated antitumor activity in pts with MET-driven PRCC (Choueiri et al. JCO 2017). The Phase III SAVOIR study (NCT03091192) further assessed savolitinib vs standard of care sunitinib in pts with MET-driven PRCC. Methods: In this open-label (sponsor blinded), randomized study, pts with centrally confirmed MET-driven ( MET and/or HGF amplification, chromosome 7 gain and/or MET kinase domain mutations), metastatic PRCC were randomized to savolitinib 600 mg once daily (QD), or sunitinib 50 mg QD 4 weeks on / 2 weeks off. Primary objective was progression-free survival (PFS; RECIST 1.1 by blinded independent central review). Secondary objectives included overall survival (OS), objective response rate (ORR), and safety and tolerability. Results: After external data on predicted PFS with sunitinib in pts with MET-driven disease became available, study enrollment was closed. At data cutoff (Aug 2019), only 60 of the planned 180 pts were randomized (savolitinib n = 33; sunitinib n = 27). Most had chromosome 7 gain (savolitinib 91%; sunitinib 96%) and no prior therapy (savolitinib 85%; sunitinib 93%). PFS, OS, and ORR were numerically improved with savolitinib vs sunitinib (Table). CTCAE grade ≥3 adverse events (AEs) were reported in 42% and 81% of pts; dose modifications were related to AEs in 30% and 74% of pts with savolitinib and sunitinib respectively. After discontinuation, 36% of all savolitinib and 19% of all sunitinib pts received subsequent anticancer therapy. Conclusions: Although pt numbers and follow-up were limited, savolitinib demonstrated encouraging efficacy and an improved safety profile vs sunitinib, with fewer grade ≥3 AEs and fewer dose modifications required. Sunitinib performance was poorer than expected based on external retrospective data. Further investigation of savolitinib as a treatment option for MET-driven PRCC is warranted. Clinical trial information: NCT03091192 . [Table: see text]

scholarly journals Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial

2020 ◽  
Vol 38 (34) ◽  
pp. 4095-4106
Author(s):  
Chunyan Lan ◽  
Jingxian Shen ◽  
Yin Wang ◽  
Jundong Li ◽  
Zhimin Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Advanced Cervical Cancer ◽  
Open Label ◽  
Duration Of Response ◽  
Grade 3

PURPOSE Camrelizumab is an antibody against programmed death protein 1. We assessed the activity and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, in patients with advanced cervical cancer. METHODS This multicenter, open-label, single-arm, phase II study enrolled patients with advanced cervical cancer who progressed after at least one line of systemic therapy. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once per day. The primary end point was objective response rate (ORR) assessed by investigators per RECIST version 1.1. Key secondary end points were progression-free survival (PFS), overall survival (OS), duration of response, and safety. RESULTS Forty-five patients were enrolled and received treatment. Median age was 51.0 years (range, 33-67 years), and 57.8% of patients had previously received two or more lines of chemotherapy for recurrent or metastatic disease. Ten patients (22.2%) had received bevacizumab. Median follow-up was 11.3 months (range, 1.0-15.5 months). ORR was 55.6% (95% CI, 40.0% to 70.4%), with two complete and 23 partial responses. Median PFS was 8.8 months (95% CI, 5.6 months to not estimable). Median duration of response and median OS were not reached. Treatment-related grade 3 or 4 adverse events (AEs) occurred in 71.1% of patients, and the most common AEs were hypertension (24.4%), anemia (20.0%), and fatigue (15.6%). The most common potential immune-related AEs included grade 1-2 hypothyroidism (22.2%) and reactive cutaneous capillary endothelial proliferation (8.9%). CONCLUSION Camrelizumab plus apatinib had promising antitumor activity and manageable toxicities in patients with advanced cervical cancer. Larger randomized controlled trials are warranted to validate our findings.

Volasertib Versus Chemotherapy in Platinum-Resistant or -Refractory Ovarian Cancer: A Randomized Phase II Groupe des Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire Study

2016 ◽  
Vol 34 (7) ◽  
pp. 706-713 ◽  
Author(s):  
Eric Pujade-Lauraine ◽  
Frédéric Selle ◽  
Béatrice Weber ◽  
Isabelle-Laure Ray-Coquard ◽  
Ignace Vergote ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Disease Control ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Progression Free Survival ◽  
Platinum Resistant ◽  
Grade 3

Purpose Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinase. This phase II trial evaluated volasertib or single-agent chemotherapy in patients with platinum-resistant or -refractory ovarian cancer who experienced failure after treatment with two or three therapy lines. Patients and Methods Patients were randomly assigned to receive either volasertib 300 mg by intravenous infusion every 3 weeks or an investigator’s choice of single-agent, nonplatinum, cytotoxic chemotherapy. The primary end point was 24-week disease control rate. Secondary end points included best overall response, progression-free survival (PFS), safety, quality of life, and exploratory biomarker analyses. Results Of the 109 patients receiving treatment, 54 received volasertib and 55 received chemotherapy; demographics were well balanced. The 24-week disease control rates for volasertib and chemotherapy were 30.6% (95% CI, 18.0% to 43.2%) and 43.1% (95% CI, 29.6% to 56.7%), respectively, with partial responses in seven (13.0%) and eight (14.5%) patients, respectively. Median PFS was 13.1 weeks and 20.6 weeks for volasertib and chemotherapy (hazard ratio, 1.01; 95% CI, 0.66 to 1.53). Six patients (11%) receiving volasertib achieved PFS fore more than 1 year, whereas no patient receiving chemotherapy achieved PFS greater than 1 year. No relationship between the expression of the biomarkers tested and their response was determined. Patients treated with volasertib experienced more grade 3 and 4 drug-related hematologic adverse events (AEs) and fewer nonhematologic AEs than did patients receiving chemotherapy. Discontinuation resulting from AEs occurred in seven (13.0%) and 15 (27.3%) patients in the volasertib and chemotherapy arms, respectively. Both arms showed similar effects on quality of life. Conclusion Single-agent volasertib showed antitumor activity in patients with ovarian cancer. AEs in patients receiving volasertib were mainly hematologic and manageable.

scholarly journals Antitumor activity and safety of camrelizumab plus famitinib in patients with platinum-resistant recurrent ovarian cancer: results from an open-label, multicenter phase 2 basket study

2022 ◽  
Vol 10 (1) ◽  
pp. e003831
Author(s):  
Lingfang Xia ◽  
Jin Peng ◽  
Ge Lou ◽  
Mei Pan ◽  
Qi Zhou ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Antitumor Activity ◽  
Safety Profile ◽  
Objective Response ◽  
Recurrent Ovarian Cancer ◽  
Synergistic Activity ◽  
Phase 2 ◽  
Open Label ◽  
Multicenter Phase ◽  
Platinum Resistant

BackgroundCombination treatments with immune-checkpoint inhibitor and antiangiogenic therapy have the potential for synergistic activity through modulation of the microenvironment and represent a notable therapeutic strategy in recurrent ovarian cancer (ROC). We report the results of camrelizumab (an anti-programmed cell death protein-1 antibody) in combination with famitinib (a receptor tyrosine kinase inhibitor) for the treatment of platinum-resistant ROC from an open-label, multicenter, phase 2 basket trial.MethodsEligible patients with platinum-resistant ROC were enrolled to receive camrelizumab (200 mg every 3 weeks by intravenous infusion) and oral famitinib (20 mg once daily). All patients had disease progression during or <6 months after their most recent platinum-based chemotherapy. Primary endpoint was confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 based on investigator’s assessment. Secondary endpoints included disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS), overall survival (OS), 12-month OS rate and safety profile.ResultsOf the 37 women enrolled, 11 (29.7%) patients had primary platinum resistant, 15 (40.5%) patients had secondary platinum resistant and 11 (29.7%) patients had primary platinum refractory disease. As the cut-off date of April 9, 2021, nine (24.3%) patients had achieved a confirmed objective response, the ORR was 24.3% (95% CI, 11.8 to 41.2) and the DCR was 54.1% (95% CI, 36.9 to 70.5). Patients with this combination regimen showed a median TTR of 2.1 months (range, 1.8–4.1) and a median DoR of 4.1 months (95% CI, 1.9 to 6.3). Median PFS was 4.1 months (95% CI, 2.1 to 5.7), and median OS was 18.9 months (95% CI, 10.8 to not reached), with the median follow-up duration of 22.0 months (range, 12.0–23.7). The estimated 12-month OS rate was 67.2% (95% CI, 49.4 to 79.9). The most common ≥grade 3 treatment-related adverse events were hypertension (32.4%), decreased neutrophil count (29.7%) and decreased platelet count (13.5%). One (2.7%) patient died of grade 5 hemorrhage that was judged possibly related to study treatment by investigator.ConclusionThe camrelizumab with famitinib combination appeared to show antitumor activity in heavily pretreated patients with platinum-resistant ROC with an acceptable safety profile. This combination might provide a novel alternative treatment strategy in platinum-resistant ROC setting and warranted further exploration.Trial registration numberNCT03827837.

The efficacy and safety of anlotinib in refractory colorectal cancer: A double-blinded, placebo controlled, randomized phase III ALTER0703 trial.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 65-65
Author(s):  
Yihebali Chi ◽  
Yongqian Shu ◽  
Yi Ba ◽  
Yuxian Bai ◽  
Baoli Qin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Placebo Group ◽  
Adverse Events ◽  
Kinase Inhibitor ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Targeting Therapy ◽  
Grade 3

65 Background: The efficacy of late line treatments for metastatic colorectal cancer (mCRC) is still limited. Antiangiogenic therapy is one of standard treatments in mCRC. Anlotinib is a multitarget tyrosine kinase inhibitor, mainly targets VEGFR1-3. This phase III trial was conducted to evaluate anti-tumor efficacy and safety of anlotinib monotherapy in refractory mCRC. Methods: Aged 18 years or older mCRC patients were enrolled in 33 Chinese hospitals. They had received at least 2 lines of chemotherapy based treatments; had ECOG PS 0-1and adequate bone marrow, liver and renal function. Enrolled patients were 2-to-1 randomly assigned into anlotinib or placebo group and stratified by previous VEGF-targeting therapy (y/n) and time from diagnosis to metastases (</≥18 months). Anlotinib (12 mg/d, oral, d1-14, q3w) or matched placebo was administered plus best supportive care. Primary end point was Overall Survival (OS). Secondary endpoints included Progression Free Survival (PFS), Objective Response Rate (ORR), Disease Control Rate (DCR), safety and quality of life. Results: Between December 2014 and August 2016, 421 patients were enrolled (282 in anlotinib and 137 in placebo group). By the cut-off date (August 31, 2018), the median OS was 8.6 months (95% CI 7.8-9.7) in anlotinib and 7.2 months (6.2-8.8) in placebo without statistical difference (p=0.87; HR=1.02 [0.82-1.27]). The median PFS in anlotinib group (4.1 months; 3.4-4.5) was significantly improved over that in placebo (1.5 months; 1.4-1.5), with a p<0.0001 and a HR of 0.34 (0.27-0.43). Improvements of ORR and DCR were observed in anlotinib over placebo (Table). In subgroup patients with RAS/KRAS/BRAF wildtype, the median OS was statistically prolonged in anlotinib (11.0 months; 8.6-14.1; n=103) than that in placebo (6.7 months; 3.5- 11.1; n=46), HR=0.68 (0.47, 0.99), p=0.043. 52.5% of patients in anlotinib and 19.7% in placebo group experienced grade 3 or above treatment related adverse events (TRAEs). The most common grade ≥3 anlotinib related adverse events were hypertension (20.9%), increased γ-GT (7.1%) and hand-foot syndrome (6.4%), which were recovered by reducing dosage. Only 2 patients in anlotinib group had grade 5 TRAE, which were both hemorrhage. Conclusions: Anlotinib could provide clinical benefits by substantially prolonged PFS with manageable toxicity for Chinese refractory mCRC patients. Although median OS did not reach significant improvement. Those with RAS/KRAS/BRAF wildtype might be the potential patients in anlotinib treatment. Clinical trial information: NCT02332499. [Table: see text]

A phase 1b/2 study of napabucasin with weekly paclitaxel in advanced, previously treated platinum resistant ovarian cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5548-5548 ◽  
Author(s):  
Carlos Becerra ◽  
Agustin A. Garcia ◽  
John L. Hays ◽  
Michael W. Method ◽  
Stephen Lane Richey ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Objective Response ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Complete Response ◽  
Dose Escalation Study ◽  
Clinical Safety ◽  
Platinum Resistant ◽  
Grade 3 ◽  
Expansion Cohort

5548 Background: Napabucasin is a first-in-class cancer stemness inhibitor, identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al PNAS 112 (6):1839, 2015). Napabucasin has shown potent synergistic preclinical anti-tumor activity with paclitaxel (PTX). In a phase Ib dose escalation study in patients (pts) with advanced solid tumors, napabucasin plus weekly PTX was well tolerated. A phase II expansion cohort was opened for patients with platinum resistant ovarian cancer. Methods: Pts with advanced ovarian cancer who had disease progression either during or in the 6 months following platinum-based systemic therapy were enrolled. napabucasin was administered orally at a starting dose of 240, 480, or 500 mg twice daily with PTX 80 mg/m2 IV weekly on 3 of every 4 weeks. AEs were evaluated using CTCAE v4.03 and objective assessments were performed per RECIST 1.1 every 8 weeks. Results: A total of 98 pts were enrolled. The average number of prior lines of systemic treatment was 3.5, including prior taxane-based therapy in 100% of patients. Treatment was well tolerated. Related grade 3 adverse events occurring ≥ 5% of pts included diarrhea (12.2%) and vomiting (5.1%). Among pts who received RECIST evaluation (n = 76), the disease control rate (DCR, proportion with SD at 8 weeks + PR + CR) was 65%, and the objective response rate (ORR, PR+CR) was 20%, with complete response in 3 pts (4%). In all patients (ITT, n = 98), the median progression-free survival (mPFS) was 3.0 months and median overall survival (mOS) was 9.3 months. Conclusions: Clinical safety and encouraging signs of anti-cancer activity, including three complete responses, were observed in pts with pre-treated platinum resistant ovarian cancer who received treatment with napabucasin plus weekly PTX. Further clinical evaluation in controlled trials is warranted. Clinical trial information: NCT01325441.

Nintedanib in metastatic appendiceal carcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS723-TPS723
Author(s):  
Birendra Kc ◽  
Mufti Naeem Ahmad ◽  
Kunal C. Kadakia ◽  
Reza Nazemzadeh ◽  
Mohamed E. Salem ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ovarian Cancer ◽  
Metastatic Colorectal Cancer ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Limited Information ◽  
Appendiceal Cancer ◽  
Open Label

TPS723 Background: Appendiceal carcinomas are rare with an incidence of about 0.12 cases per 1,000,000 people per year. There is limited, mostly retrospective data in the treatment of metastatic appendiceal carcinomas. Generally, fluoropyrimidine-based therapy is used in the first line, adapting regimens for metastatic colorectal cancer. However, beyond progression, no treatments have shown clear activity. In appendiceal cancer, high vascular endothelial growth factor receptor (VEGFR)2 expression has been correlated with poor survival. Moreover, malignant ascites has been demonstrated to have elevated levels of VEGF. Nintedanib is an oral tyrosine kinase inhibitor of VEGFR which demonstrated activity in lung and ovarian cancer in clinical trials, and has undergone investigation in heavily pretreated metastatic colorectal cancer. Given the analogies between appendiceal and colorectal cancer and potentially ovarian cancer, and the limited information about the optimal treatment of metastatic appendiceal carcinomas, further investigation with nintedanib is warranted. Methods: This is a single arm, open label, investigator initiated, two-stage phase II trial (NCT 03287947) in metastatic appendiceal cancer patients after failure (defined as progression on or within 6 months or intolerance) of initial fluoropyrimidine-based therapy and at least one measurable site of disease. The trial started enrolling patients in June 2018, and up to 39 subjects will be enrolled. They will be treated with 200 mg of oral nintedanib twice daily and undergo disease evaluation every two months. The primary objective of this study is to evaluate the disease control rate (DCR), the composite of objective response and stable disease per RECIST 1.1. Secondary objectives include evaluation of safety and toxicity, objective response rate (ORR), 6-month progression free survival (PFS) and overall survival (OS). DCR, ORR & 6-month PFS will be estimated with the corresponding 95% Clopper-Pearson confidence interval. PFS & OS will be estimated using Kaplan-Meier techniques. Exploratory objectives include evaluation of serum VEGF, ascites VEGF, hypertension and paracentesis frequency in subjects with ascites at study entry. Clinical trial information: NCT 03287947.

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