Poster display session Poster Display

306P - Efficacy and safety of apatinib in heavily pretreated metastatic adenocarcinoma of the head and neck

Presentation Number
306P
Lecture Time
06:00 PM - 06:00 PM
Session Name
Speakers
  • Lin Gui
Location
Exhibition area, Singapore, Singapore, Singapore
Date
Sat, 23.11.2019
Time
06:00 PM - 07:00 PM
Authors
  • Lin Gui
  • Xiaohui He

Abstract

Background

The optimal therapy for adenocarcinoma of the head and neck with distant metastasis is very limited and controversial. Although antiangiogenic therapy is effective in advanced lung, colon, hepatic, and renal carcinomas, limited is known about its value in the carcinoma of the head and neck. Apatinib, an oral, highly potent tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2), has been proven to be effective for the treatment of a broad range of advanced solid tumors. This prospective phase II study (NCT02989259) aims to investigate the efficacy and safety of apatinib in heavily pretreated patients with metastatic adenocarcinoma of the head and neck.

Methods

This study enrolled patients with adenocarcinoma of the head and neck, who failed in the metastatic setting at least one prior chemotherapy regimen. The primary end point was progression free survival (PFS). Secondary end points included objective response rate, disease control rate, overall survival (OS), and safety. Patients were treated with apatinib 500 mg daily until disease progression or the occurrence of intolerable toxicity. Efficacy was assessed every 8 weeks.

Results

From December 2016 to January 2019, twenty patients were enrolled, including 13 males and 7 females, with a median age of 61 years (26-79). The median number of previous chemotherapy regimens for the metastatic diseases was 2 (1-3). Partial response was achieved by 5 (25%) patients and stable disease exhibited by 14 (70%) patients.The median PFS and OS were 7.5 and 11.0 months, respectively. The most common adverse events (AEs) of all grade were secondary hypertension (n = 16), proteinuria(n = 10), hyperbilirubinemia (n = 10), nausea (n = 6), fatigue (n = 5) and hand-foot syndrome (n = 4). Grade 3/4 AEs were hypertension (n = 4), oral microsites (n = 3), and thrombocytopenia (n = 1). No grade 4 or 5 AE was observed in the study.

Conclusions

Our results indicated that apatinib exhibited objective efficacy in heavily pretreated, metastatic adenocarcinoma of the head and neck with a manageable toxicity profile. Apatinib can be considered as a treatment option for adenocarcinoma of the head and neck with metastatic diseases.

Clinical trial identification

The trial protocol number is NCT02989259. And release date is December 2016.

Legal entity responsible for the study

CAMS & PUMC, National Cancer Center, Cancer Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session Poster Display

508P - Efficacy and safety of anti-PD-1 antibody SHR-1210 combined with apatinib in first-line treatment for advanced lung squamous carcinoma: A phase II study

Presentation Number
508P
Lecture Time
06:00 PM - 06:00 PM
Session Name
Speakers
  • Jinliang Wang
Location
Exhibition area, Singapore, Singapore, Singapore
Date
Sat, 23.11.2019
Time
06:00 PM - 07:00 PM
Authors
  • Jinliang Wang
  • Zhibo Zhang
  • Fan Zhang
  • Qi Song
  • Li Zhang
  • Zhefeng Liu
  • Junxun Ma
  • Xiang Yan
  • Lijie Wang
  • Haitao Tao
  • Sujie Zhang
  • Xiaoyan Li
  • Xiaoyu Zhi
  • Yi Hu
  • Shunchang Jiao

Abstract

Background

PD-1 antibody plus chemotherapy is a standard first-line therapy in patients with advanced lung squamous carcinoma. Previous study suggested that the combination of anti-PD-1 antibody SHR-1210 and VEGFR 2 inhibitor apatinib significantly improved antitumor effects. The aim of this study was to evaluate the efficacy and safety of SHR-1210 in combination with apatinib for advanced lung squamous carcinoma patients as a first-line treatment.

Methods

Stage IIIB or IV advanced lung squamous carcinoma patients were enrolled in this open-label, single-center, single-arm phase II study. Patients received SHR-1210 (200mg q2w) and apatinib (250mg po qd) until progression or unacceptable toxicity. Treatment efficacy was assessed every 3 cycles (6 weeks). The primary end point is progression-free survival (PFS). Secondary end points are objective response rate (ORR), disease control rate (DCR) and overall survival (OS), which according to RECIST 1.1.

Results

At data cut-off (July 8, 2019), 12 advanced lung squamous carcinoma patients were enrolled in the study, of which 7 patients were evaluable. Median age was 67 years, male accounts for 91.7% (11/12), clinical stage IV for 83.3% (10/12). All included patients at a median follow-up of 2.3 months (range 0.4-6.5 months). No patient achieved complete response (CR). Partial response (PR) was achieved by 6 (85.7%) patients and stable disease (SD) exhibited by 1 (14.3%) patient. The ORR and DCR were 85.7% and 100%, respectively. Grade II adverse events were observed in 4 (33.3%) patients with interstitial pneumonia (1 patient), hand-foot skin reaction (2 patients) or rash (1 patient) . One patient (1/12) died after 6 months treatment due to interstitial pneumonia and one patient was assessed by PD after 5.5 months treatment. Four patients ever suspended treatment due to interstitial pneumonia, pyelonephritis, rash or pneumothorax.

Conclusions

The combination of SHR-1210 and apatinib for advanced lung squamous carcinoma patients may be a promising method as a first-line treatment.

Clinical trial identification

ChiCTR1800019329 (Chinese Clinical Tiral Registry). Date of Registration: 2018-11-06.

Legal entity responsible for the study

Jinliang, Wang.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session Poster Display

340TiP - A multicenter, randomized, controlled, phase II trial exploring adjuvant combined therapy of apatinib and SHR-1210 (anti-PD-1), in patients with hepatocellular carcinoma at high risk of recurrence after radical resection

Presentation Number
340TiP
Lecture Time
06:00 PM - 06:00 PM
Session Name
Speakers
  • Shida Yan
Location
Exhibition area, Singapore, Singapore, Singapore
Date
Sat, 23.11.2019
Time
06:00 PM - 07:00 PM
Authors
  • Shida Yan
  • Yubao Zhang
  • Xinyu Bi
  • Jianjun Zhao
  • Shunda Du
  • Zhen Huang
  • Yefan Zhang
  • Dongbin Liu
  • Zhiyu Li
  • Jianguo Zhou
  • Jianqiang Cai
  • Hong Zhao

Abstract

Background

Hepatocellular carcinoma (HCC) is the most common malignancy with high rates of recurrence and metastasis after radical resection. Vascular invasion, including portal vein tumor thrombus (PVTT) and microvascular invasion (MVI), and microsatellite lesions are two significant risk factors of postoperative recurrence and metastasis for HCC. Therefore, it is necessary to discover adjuvant therapies for patients with these risk factors. Anti-angiogenesis therapy combined with immunotherapy has demonstrated clinical benefits in multiple advanced solid neoplasms, including HCC. An exploratory phase Ib study (NCT02942329) proved that combined therapy of apatinib (250mg QD) and anti-PD-1 drug, SHR-1210 (200mg Q2W) was well tolerated and had preliminary efficacy in advanced HCC.

Trial design

This multicenter, randomized, controlled, phase II study will evaluate the safety and efficacy of adjuvant combined therapy of apatinib and anti-PD-1 drug, SHR-1210, compared with hepatic arterial infusion (HAI) chemotherapy, in patients with HCC at high risk of recurrence after radical resection. 200 patients, aged >18 years, Child-Pugh score 0 or 1, with histologically confirmed primary HCC, BCLC stage A or B diseases that are radical resected without other prior therapy for HCC and who are found to have microsatellite lesions, microvascular invasion or PVTT involved in second-order branch or above by preoperative imaging examination or postoperative pathological findings will be recruited and randomized (1:1) to receive apatinib (250mg QD) and SHR-1210 (200mg Q2W) for 6 months, or 2 times of standard HAI treatments (epirubicin 80-100mg or epirubicin 50mg+oxaliplatin 50mg). The primary endpoint is to compare recurrence-free survival and secondary endpoints include overall survival, safety, 1,2,3-year recurrence rate and Quality of Life score (QoL). Survival follow-up will continue for up to 3 years. The study is ongoing.

Clinical trial identification

NCT 03839550.

Legal entity responsible for the study

National Cancer Center/Cancer Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster display session Poster Display

526P - A phase II study of apatinib in patients with recurrent/metastatic esophageal squamous cell carcinoma (ESCC)

Presentation Number
526P
Lecture Time
06:00 PM - 06:00 PM
Session Name
Speakers
  • Li Chu
Location
Exhibition area, Singapore, Singapore, Singapore
Date
Sat, 23.11.2019
Time
06:00 PM - 07:00 PM
Authors
  • Li Chu
  • Fei Liang
  • Junhua Zhang
  • Jiaying Deng
  • Yun Chen
  • Qi Liu
  • Dashan Ai
  • Zhengfei Zhu
  • Kuaile Zhao

Abstract

Background

No standard treatment strategy for patients with recurrent/metastatic esophageal squamous cell carcinoma (ESCC) experiencing progression after one or more lines of chemotherapy. The aim of this study was to assess the efficacy and safety of apatinib, an oral vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase inhibitor, in patients with recurrent/metastatic ESCC for whom at least one line of prior chemotherapy had failed.

Methods

This was a phase II trial that enrolled patients with recurrent/metastatic ESCC who had evidence of disease progression after first-line or more lines chemotherapy. All patients received continuous apatinib 500mg once daily until disease progression, death, or intolerable toxicity, dose escalation was allowed. The primary end point was progression free survival (PFS).

Results

Between July 2017 and August 2018, 40 patients were recruited. Data was cutoff at June 26, 2019. Among the 40 patients, 5 patients achieved partial response while 21 had stable disease. Primary end point median PFS (mPFS) was 113 days (95% 45-180). Median OS (mOS) was 158 days (95% 101-215), Objective response rate (ORR) was 12.5%. The incidence of drug-related adverse events (AEs) was 87.5%. 40.0% patients developed severe AEs. Main AEs were Fatigue (37.5%), Hand-foot syndrome (27.5%) and Hypertension (25%). Two patients with massive hemoptysis, and two patients with tracheal esophageal fistula had the uncontrolled primary tumor or trachea/bronchi eroded.

Conclusions

The study confirmed that apatinib was effective as second-line or more lines treatment for recurrent/metastatic ESCC patients, and most adverse effect were acceptable. However, patients with uncontrolled primary tumor or trachea/bronchi eroded should been cautiously considered to use.

Clinical trial identification

NCT03274011.

Legal entity responsible for the study

Fudan University Shanghai Cancer Center.

Funding

Jiangsu Hengrui Medicine.

Disclosure

All authors have declared no conflicts of interest.

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Mini Oral session - Sarcoma Mini Oral session

406O - VEGFR2 Polymorphisms as Novel Biomarker of Anti-angiogenic Therapy for Pediatric and Young Adult Sarcoma

Presentation Number
406O
Lecture Time
12:05 PM - 12:10 PM
Speakers
  • Qiyuan Bao
Location
Room 311, Singapore, Singapore, Singapore
Date
Fri, 22.11.2019
Time
11:40 AM - 12:20 PM
Authors
  • Qiyuan Bao
  • Yuehao Hu
  • Junxiang Wen
  • Yuhui Shen
  • Weibin Zhang

Abstract

Background

The impact of germline mutations of the angiogenesis pathways on the therapeutic response has been extensively studied for the carcinoma population. However, such information is almost unknown for pediatric and young adult’s sarcoma, for which the field has seen the rapid growing popularity of the use of the anti-angiogenic therapy.

Methods

In this study, we retrospectively analyzed 79 tissue sarcoma patients less than 45 yrs receiving anti-angiogenic therapy (apatinib). In 67 (84%) of these patients, twenty previously reported single nuclear polymorphism (SNPs) in angiogenesis pathway were genotyped to screen for potential toxicity and predictive biomarkers.

Results

The mean 6 mo PFS rate was 64%, with the duration of response varying from no response to more than 26 months. Multivariate analysis indicated that hand-foot reactions, hair depigmentation and spontaneously pneumothorax (SP) remain independent toxicity biomarker for greater PFS. Interestingly, we observed a strong correlation of ITGA2 rs1126643 polymorphism vs surgical wound complications (C/C 4% vs C/T 24% vs T/T 33%, p = 0.008) as well as SP (C/C 13.8% vs C/T 36.4% vs T/T 66%), suggesting that Integrin mechanism might underline both toxicities. Moreover, VEGFR2 rs2071559 polymorphism remains the only sensitivity biomarker for mPFS (mutation vs WT, 12 mo vs 5 mo), regardless of the sarcoma subtypes. Surprisingly, such mutations were to be associated with the incidence of hair depigmentation (R = 0.398, p = 0.026), further supporting that hair discoloration is a mechanism-based toxicity biomarker. Moreover, a significant higher frequecies of such two mutations (0.53 for ITGA polymorphism, 0.59 for VEGFR2 polymorphism) in our cohort than general Han Chinese (1000G project database) suggest a theoretical impact on the sarcomagenesis.

Conclusions

Our study is the first one examining the angiogenesis germline polymorphism for the younger population in bone and soft tissue cancer. VEGFR2 (rs2071559) as well as ITGA (rs1126643) might serve as pan-sarcoma biomarkers for VEGFR2 targeted therapy and warrant further validation for its biological and clinical implications.

Legal entity responsible for the study

Ruijin Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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