- Amanda Psyrri (Athens, Greece)
- Brigette B. Ma (Sha Tin, Hong Kong PRC)
265O - Anlotinib in locally advanced or metastatic radioiodine-refractory differentiated thyroid carcinoma: A randomized, double-blind, multicenter phase II trial (ID 605)
- Yihebali Chi (Beijing, China)
Abstract
Background
Anlotinib is a novel multikinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. This study investigated the potency of anlotinib in treating locally advanced or metastatic radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC).
Methods
This is a randomized, double-blind, placebo-controlled, multicenter phase II trial (NCT02586337). Eligible pts were 18-70 years old with measurable, pathologically confirmed locally advanced or metastatic RAIR-DTC. Pts who had received previous anlotinib or other VEGFR-TKIs were excluded. Pts were randomized in a 2:1 ratio to receive anlotinib or placebo with a dose of 12mg QD for 2 weeks followed by a week of rest (2/1 schedule). The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Pts in placebo arm were allowed to receive open-label anlotinib after disease progression.
Results
Between September 2015 and August 2018, 113 pts (76 in anlotinib arm and 37 in placebo arm) were enrolled. The data cutoff date for primary endpoint was January 1, 2020. The research met its primary endpoint that the median PFS was 40.54 months (95% CI 28.29, NE) in anlotinib arm and 8.38 months (95% CI 5.59, 13.80) in placebo arm (p < 0.0001). The HR was 0.21 (95% CI 0.12, 0.37). The ORR was 59.21% in anlotinib arm and no response was observed in placebo arm (p < 0.0001). In addition, significant DCR benefit was observed for anlotinib treatment (anlotinib arm vs. placebo arm = 97.37% vs. 78.38%, p = 0.002). The OS data was still in follow-up. All pts in anlotinib arm and 97.30% pts in placebo arm experienced adverse events (p = 0.327). The incidence of treatment-related AEs of two groups was 100.00% and 86.49% (p = 0.003). Serious treatment-related AEs occurred in 15.79% pts received anlotinib. The most common AEs in anlotinib arm were hypertension (84.21%) and hypertriglyceridemia (68.42%).
Conclusions
The study demonstrates the efficacy and safety of anlotinib and supports its use as a new option for the treatment of locally advanced or metastatic RAIR-DTC.
Clinical trial identification
NCT02586337.
Legal entity responsible for the study
Chia Tai TianQing Pharmaceutical Group Co., Ltd.
Funding
Chia Tai TianQing Pharmaceutical Group Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.
266O - Combination ipilimumab and nivolumab in recurrent/metastatic nasopharyngeal carcinoma (R/M NPC): Updated efficacy and safety analysis of NCT03097939 (ID 1030)
- Hsiang-Fong Kao (Taipei, Taiwan)
Abstract
Background
Nasopharyngeal cancer (NPC) is common in Southeast Asia and Southern China. It is infiltrated by T-regulatory cells and shows high expression of PD-L1. However, monotherapy PD-1/PD-L1 activity is limited and not superior to salvage combination chemotherapy. We hypothesized that CTLA-4 blockade would suppress T-regulatory function and complement PD-1 blockade. We update the efficacy and safety from the first phase II study of this combination in NPC.
Methods
A single arm phase II of a Simon 2-stage design was used, with preplanned expansion for safety and efficacy. Pts were treated with Nivolumab 3 mg/kg q2 weeks, and Ipilimumab 1 mg/kg q6 weeks. Eligible pts had R/M NPC, measurable plasma EBV DNA, no more than 1 prior line of chemotherapy, ECOG 0-1, and adequate organ function. All pts who met the eligibility criteria and received at least one dose of the combination drugs were included in the safety and efficacy analysis. The primary efficacy endpoint was best overall response (BOR) by RECIST 1.1. Toxicity was assessed using CTCAE criteria.
Results
Forty pts were enrolled between July 2017 and September 2019 across Taiwan and Singapore (data cut-off February 2020). Median age was 53 years (23-73 years). Most (90.0%) were of Chinese ethnicity and 33 (82.5%) were male. Thirty-nine pts (97.5%) had prior chemotherapy treatment. Six (15%) pts remain on study. The median number of cycles received was 4. Overall, 12 pts had a BOR of PR (30%; 95% CI 16.6%-46.5%). The median duration of response (DOR) was 5.9 months (95% CI 3.95-8.97 months). With a median follow up of 17.3 months, median PFS was 5.3 months (95% CI 3.0-6.4 months) and median OS was 17.6 months (95% CI 13.1-30.0). Thirty-four pts (85%) experienced treatment-related (Tr) events. Common TrAEs included maculopapular rash (n=16; 40%) and hypothyroidism (n=11; 28%). Four (10%) pts experienced Grade 3/4 TrSAEs including hypocortisolism, pneumonia, myasthenia gravis, and raised lipase. There was no relationship of tumor mutation burden/PD-1 expression to response.
Conclusions
Combination Nivolumab/Ipilimumab is active and safe in NPC, with durable responses and PFS, presenting a possible alternative to salvage chemotherapy.
Clinical trial identification
NCT03097939.
Legal entity responsible for the study
The authors.
Funding
Bristol-Myers Squibb; Ono pharmaceuticals.
Disclosure
All authors have declared no conflicts of interest.
267O - Distinct phenotypes of locoregionally advanced (LA-NPC) harbor disparate survival outcomes and are associated with germline variants (ID 961)
- Enya Ong (Singapore, Singapore)
Abstract
Background
LA-NPC can be subtyped by ascending (A; T3-4N0-1), descending (D; T1-2N2-3) and ascending-descending (AD; T3-4N2-3) at diagnosis, depending on the extent of tumor spread. These phenotypes differ by prognoses, but germline and somatic molecular drivers underpinning their tumorigenesis are unknown. We aimed to validate the A and AD subtypes of LA-NPC and investigate for germline variants that are associated with them.
Methods
We utilized a cohort of 255 patients with biopsy-proven, non-metastatic, T3-4 NPC (AJCC/UICC 8th edition). Association of clinical covariates were tested by Cox regression. Germline profiling was conducted by whole exome sequencing (100x; Illumina NovaSeq) and variants were shortlisted based on known/predicted pathogenicity. The differential prevalence of variants was tested using Fisher’s exact test.
Results
Median follow-up duration of the cohort was 79 (IQR: 66-90) mo; median age was 49.4 (43.2-58.1) y. We identified 108 (42.3%) A- and 147 (57.6%) AD-subtype in our cohort. 55 (50.9%) and 35 (32.4%) of the A-subtype patients compared to 64 (43.5%) and 75 (51.0%) in the AD-subgroup received chemoradiotherapy (CRT) alone and CRT+induction/adjuvant chemotherapy, respectively. High EBV DNA titer of >4000 copies were more frequent in the AD- than A-subgroup (50.0% vs 31.2%, P = 0.0141). 5-y DFS differed between the A and AD subtypes (85.1% [95% CI: 78.2-92.7] vs 67.0% [59.2-75.8%], P <0.001); the AD-subtype was significantly associated with worse DFS (HR 3.10 [1.54-6.23], P = 0.00147) after adjustment for age, EBV DNA and T4-status. Next, we observed germline variants in hallmark-of-cancer genes (FAT1 [N=46; 18.0%] and NOTCH1 [N=13; 5.1%]), DNA repair genes (SRSF6 [N=13; 5.1%] and POLD1 [N=14; 5.5%]) and genes with known association to NPC (MST1R [N=13; 5.1%] and SYNE1[N=50; 19.6%]). Of them, TGFBR2 variants were significantly associated with the unfavorable AD-subtype (OR 3.68 [1.06-15.3], P = 0.041).
Conclusions
We have shown that the AD-subtype in patients with LA-NPC is associated with an inferior DFS. The TGFBR2germline variants may be associated with the susceptibility of this unfavorable phenotype.
Clinical trial identification
CIRB Ref. No.: 2019/2177.
Legal entity responsible for the study
The authors.
Funding
National Medical Research Council.
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant abstracts 265O, 266O and 267O (ID 1111)
- Ingeborg Tinhofer-Keilholz (Berlin, Germany)
LIVE Q&A (ID 1114)
- Amanda Psyrri (Athens, Greece)
268MO - A phase-Ib study of lucitanib (AL3810) in a cohort of patients with recurrent and metastatic nasopharyngeal carcinoma (NPC) (ID 946)
- Hong-yun Zhao (guangzhou, China)
Abstract
Background
There remains no standard therapy for patients with multiply pretreated recurrent and metastatic NPC. Overexpression of VEGFR and FGFR is common in NPC and the higher expression is related to poor prognosis. This feature makes NPC potentially suitable for antiangiogenic treatment. AL3810 is a novel multi-target inhibitor of VEGFR1-3, FGFR1-3, and PDGFRα/β. Preliminary data from the phase-Ib, randomized, noncomparative, open label trial are presented showing the safety and efficacy of AL3810 in patients with pretreated recurrent and metastatic NPC.
Methods
Eligible patients were required to have histologically confirmed undifferentiated NPC with measurable lesion according to RECIST 1.1. They had to receive at least 1 prior line of treatment and recurred at locoregional and/or distant sites. All patients were randomized into a continuous (Arm A, 10 mg QD) or intermittent (Arm B, 3 weeks on/1 week off, 10 mg QD) AL3810 dosing arm. The primary endpoint is safety profile. Secondary endpoints include objective response rate (ORR) and disease control rate (DCR).
Results
A total of 20 patients (10 patients in each arm) have been enrolled to date with a median age of 47 years. The median number of prior systemic treatments was 3. The most common drug-related grade 3 or worse TEAEs were hypertension (3/10 in Arm A, 0/10 in Arm B), proteinuria (2/10 in Arm A, 0/10 in Arm B). With appropriate supportive treatment, dose reduction and/or temporary discontinuation, The ≥ grade 3 TEAEs were all manageable. The confirmed ORR was 20% in Arm A, and 10% in Arm B. The DCR was 90% in Arm A vs 60% in Arm B. As of the date of this publication, 2 patients are still receiving AL3810 treatment and one of them in arm A had partial response lasting > 32 months. Detail efficacy outcomes are shown in the below table.
Arm A (n=10) n (%) Arm B (n=10) n (%) Total (n=20) n (%) CR 0 0 0 PR 2 (20) 1 (10) 3 (15) SD 7 (70) 5 (50) 12 (60) PD 1 (10) 3 (30) 4 (20) Not applicable 0 1 (10) 1 (5) ORR (CR + PR) 2 (20) 1 (10) 3 (15) DCR (CR + PR +SD) 9 (90) 6 (60) 15 (75)
Conclusions
AL3810 has promising activity and tolerable safety profile in pre-heavily treated NPC. Additional evaluation in a randomized trial with larger sample size is warranted.
Clinical trial identification
NCT03260179.
Legal entity responsible for the study
Shanghai HaiHe Pharmaceutical Co., Ltd.
Funding
Shanghai HaiHe Pharmaceutical Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.
269MO - Comparison of three induction chemotherapy regimens with gemcitabine plus cisplatin, cisplatin plus fluorouracil, and cisplatin plus capecitabine for locoregionally advanced nasopharyngeal carcinoma: A pooled analysis of two prospective studies (ID 444)
- Sik Kwan Chan (Hong Kong, Hong Kong PRC)
Abstract
Background
We report the results of our prospective study comparing the differences in efficacy and safety between three induction chemotherapy regimens of gemcitabine plus cisplatin (GP), cisplatin plus fluorouracil (PF) and cisplatin plus capecitabine (PX) in previously untreated locoregionally advanced nasopharyngeal carcinoma (NPC).
Methods
Induction chemotherapy with either GP (from our prospective observational study), PF or PX (from NPC-0501 study) was given in prospectively recruited patients who had previously untreated locoregionally advanced (stage III to IVA) NPC. The primary study objectives included locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). The secondary objectives were major treatment-related toxicities (grade ≥ 3), both acute and late.
Results
From 2006 to 2016, 278 patients were enrolled (84, 94 and 100 patients in GP, PF and PX group respectively). After a median follow-up duration of 80 months, the 3-year LRFS, DMFS, PFS, CSS and OS of the whole population were 84.9%, 80.9%, 78.7%, 89.8% and 88.1% respectively. There were no statistically significant difference in pre-specified survival endpoints between GP, PF and PX group in both stage III and stage IVA patients. GP group had a lower incidence of severe (grade 3 or 4) anaemia and diarrhoea in stage III patients; and severe anaemia, dehydration, renal impairment and vomiting in stage IVA patients. The incidences of grade 3 or 4 late toxic effects were similar between 3 induction regimen groups.
Conclusions
GP had similar efficacy and potentially fewer complications as compared with PF and PX.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
270MO - A single-arm, open-label, multicenter phase II study of camrelizumab in patients with recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC) who had progressed on ≥2 lines of chemotherapy: CAPTAIN study (ID 890)
- Li Zhang (Guangzhou, China)
Abstract
Background
The management of R/M NPC remains a challenge worldwide due to its poor prognosis and limited treatment option after prior chemotherapy. Camrelizumab, a humanized anti–PD-1 antibody, had shown favorable anti-tumor activity and manageable toxicities in R/M NPC in previous phase I trial (Fang et al. Lancet Oncol 2018). We conducted this phase II trial (CAPTAIN) to further assess the efficacy and safety of camrelizumab in R/M NPC.
Methods
Patients with histologically confirmed R/M NPC (stage IVb) who had progressed on ≥2 lines of chemotherapy were enrolled and received camrelizumab at 200 mg IV q2w. The primary endpoint was ORR assessed by independent review committee (IRC) per RECIST v1.1.
Results
From Aug 14, 2018 to Dec 30, 2019, 156 eligible patients were enrolled and received camrelizumab treatment. As of data cutoff on Jun 30, 2020, the median follow-up time was 10.9 months (range 0.7–22.3). Of the 156 patients, 44 (28.2%, 95% CI 21.3–36.0) patients had objective responses assessed by IRC, including one complete response and 43 partial responses. Median DoR was not reached (95% CI 9.5–not estimable), and the 12-month DoR rate was 58.5% (95% CI 37.3–74.8). Median PFS per IRC was 3.7 months (95% CI 2.0–4.1) and median OS was 17.1 months (95% CI 15.1–not estimable). Treatment-related adverse events (TRAEs) of any grade were observed in 151 (96.8%) of the 156 patients. TRAEs of grade ≥3 occurred in 23 (14.7%) patients, with the most common ones being increased gamma-glutamyl transferase (3.2%) and anaemia (3.2%). Treatment interruption and discontinuation due to TRAEs occurred in 18 (11.5%) and two (1.3%) patients, respectively. Eighteen (11.5%) patients had serious TRAEs, and one death was considered as drug-related. Plasma Epstein-Barr virus DNA for biomarker analysis were obtained and the result will be presented at the meeting.
Conclusions
Camrelizumab demonstrated promising anti-tumor activity and favorable safety profile in patients with R/M NPC who had progressed on ≥2 lines of chemotherapy, thus could represent a novel treatment option for this patient population.
Clinical trial identification
NCT03558191; CTR20180865.
Legal entity responsible for the study
Jiangsu Hengrui Medicine Co., Ltd.
Funding
Jiangsu Hengrui Medicine Co., Ltd.
Disclosure
Q. Yang, B. Zhang: Full/Part-time employment: Jiangsu Hengui Medicine Co., Ltd. All other authors have declared no conflicts of interest.
Invited Discussant abstracts 268MO, 269MO and 270MO (ID 1117)
- Edwin P. Hui (Sha Tin, Hong Kong PRC)
LIVE Q&A (ID 1118)
- Amanda Psyrri (Athens, Greece)