Compared with cutaneous melanoma, mucosal melanoma is a more aggressive malignancy with a high rate of distant metastases. Median overall survival (OS) is less than 12 months and mucosal melanoma appears to be largely resistant to traditional therapies, including immunotherapy. Expression of vascular endothelial growth factor (VEGF) has been shown to be associated with poor outcomes in patients with mucosal melanoma [1].
In the reported phase 1B study, the safety and efficacy of first-line treatment with the VEGFR inhibitor axitinib in combination with the anti-PD1 antibody toripalimab (approved in China for second-line treatment of metastatic melanoma) were evaluated [2]. Primary endpoint of the study was the dose-limiting toxicity; secondary endpoints included adverse events, objective response rate, duration of response, progression-free survival (PFS), and OS. In the dose-escalation part of the study 6 patients were enrolled; in the dose-expansion part of the study 33 patients were enrolled (60% female, >90% had no prior systemic chemotherapy). Patients were treated with axitinib (5 mg twice daily) plus toripalimab (3 mg/kg every 2 weeks).
The objective response rate was 48.5%: 1 patient had a complete response, 15 had a partial response, and 10 patients had stable disease. The median duration of response was 13.7 months, median PFS was 7.5 months (95% CI 3.9-14.8), median OS was 20.7 months (95% CI 10.2-not yet reached); 1-year OS rate was 65.5% and 2-year OS rate was 44.8%. Positive PD-L1 status (>1%) as well as tumour mutation burden ≥1 mut/Mbp were associated with a higher objective response rate, longer PFS, and a longer OS (not statistically significant due to the low numbers of patients). A combined gene expression profile of 12 genes – including genes related to inflammation and angiogenesis – was positively associated with response to axitinib plus toripalimab.
The combination therapy was well tolerated and no dose-limiting toxicities were observed in the initial 6 patients. Almost all patients in the dose-expansion part (32/33) experienced treatment-related adverse events, 13 patients (39%) experienced grade ≥3 treatment-related adverse events. Most prominent treatment-related adverse events grade ≥3 were proteinuria (n=3), hypertension (n=3), and neutropenia (n=3).
- Simonetti O, et al. Anticancer Res. 2015; 35: 2113-2120.
- Sheng X, et al. ASCO Virtual Meeting, 29-31 May 2020, Abstract 10007
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Table of Contents: ASCO 2020
Featured articles
COVID-19 & Telemedicine
COVID-19 and Cancer Consortium Registry: initial results
Oncology hospital-at-home model reduces hospitalizations, emergency department visits, and costs
Nurse-led telephone triage system reduces hospitalizations, helps patients manage symptoms at home
Melanoma
Adjuvant pembrolizumab: durable RFS for stage III melanoma
Adjuvant pembrolizumab: durable RFS for stage III melanoma
Pembrolizumab plus low-dose ipilimumab well tolerated after progression on PD1 antibody therapy
Toripalimab plus axitinib effective in metastatic mucosal melanoma
Breast & Ovarian Cancer
Advanced breast cancer: locoregional therapy does not improve OS
T-DM1 does not improve safety or efficacy in HER-2 positive early breast cancer; favorable iDFS reported
Maintenance olaparib improves OS in relapsed ovarian cancer with BRCA1/2 mutation
Combination pembrolizumab/chemo improves PFS in metastatic TNBC
Effect of veliparib with or without cisplatin in breast cancer: results of SWOG S1416
PHOEBE, a phase 3 trial comparing pyrotinib and lapatinib in HER2-positive metastatic breast cancer
BYLieve demonstrates efficacy of PIK3CA-directed treatment post CDK4/6-ihibition
Strategies emerge for chemotherapy de-escalation in HER2-positive breast cancer
Multiple Myeloma
Carfilzomib: no PFS benefit for multiple myeloma
Lung Cancer
ES-SCLC: tremelimumab + durvalumab + chemotherapy misses endpoint
Adjuvant osimertinib in NSCLC: practice changing ADAURA trial
ES-SCLC: pembrolizumab KEYNOTE-604 data
Second-line gemcitabine plus ramucirumab significantly improves overall survival
Tiragolumab and atezolizumab: ORR in NSCLC
MET-amplified advanced NSCLC responds well to MET inhibitor capmatinib
Genitourinary Cancer
Urothelial cancer: avelumab works as maintenance therapy
ARAMIS final OS and nmCRPC safety outcomes
Final survival results from phase 3 SPARTAN trial
Novel drug for kidney cancers/VHL patients
Primary analysis from IMvigor010, adjuvant atezolizumab in high risk muscle-invasive urothelial carcinoma
First randomised trial of Lu-PSMA in mCRPC progressing after docetaxel
Gastrointestinal Cancer
HER2-expressing metastatic colorectal cancer: trastuzumab deruxtecan
REGOMUNE: a phase 2 study combining regorafenib and avelumab
Cardiotoxicity: consider switching to S-1
Perioperative chemotherapy for resectable pancreatic ductal adenocarcinoma
Real-world data of sequential sorafenib followed by regorafenib in unresectable HCC
Paediatric Cancer
Sustained improvements in quality of life with larotrectinib
Promising first immunotherapy trial in placental trophoblastic tumours
Precision medicine for poor-prognosis paediatric patients
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