Abstract 3567
Background
AcSé Pembrolizumab is a Phase II, non-randomized parallel arm, open-label, multicentric study investigating the efficacy and safety of pembrolizumab monotherapy in patients with rare cancers (NCT03012620). Here we report the first results of pembrolizumab in the sarcoma arm including chordomas, alveolar soft part sarcoma (ASPS), rhabdoid tumors, SMARCA4 deficient sarcomas and desmoplastic small round cell tumors (DSRCT).
Methods
Selected histotypes were all rare sarcomas (incidence <0.2/100000/year). Main inclusion criteria were age>18, PS ≤ 1, and advanced disease resistant to standard treatment. Patients received pembrolizumab 200 mg IV as a 30-minute infusion on Day 1 of every 21-day cycle for a maximum of 2 years. The primary endpoint was the confirmed objective response rate according to RECIST v1.1. Secondary endpoints included clinical benefit rate, duration of response, progression-free survival (PFS), overall survival (OS), and safety.
Results
21 patients with a primary diagnosis of chordoma (n = 12, 57%), ASPS (n = 6, 28%), or DSRCT, rhabdoid tumor and SMARCA4-deficient sarcoma (n = 3, 15%) were included from October 2017 to October 2018. The median number of cycle was 11 (range 1-23) with 9 (42.9%) patients who discontinued the trial after a median of 5 cycles. Three patients died after a median of 2 cycles due to progression (n = 2) or an unrelated cause (n = 1, trauma). For the population, the complete response/partial response (PR)/stable disease (SD) rates was 85% with 3 (15%) patients who achieved PR (DSRCT, rhabdoid, chordoma) and 16 (80%) with SD, after a median follow-up of 7.7 months (range 0-15.2). The median PFS was 11.5 months, the 6-month PFS was 61.5% and the 6-month OS was 85.2%. In subgroup analyses, the median PFS was 5.7 months for patients with chordoma and not reached for patients with ASPS. The 6-month OS rate was 75% in chordomas and 100% in the ASPS cohort. The basal clinical (histology) or biological (potassium, C-reactive protein, and lymphocyte levels) parameters tested were not predictive factors of PFS. The toxicity profile was similar to that observed in other cancers.
Conclusions
Pembrolizumab shows high levels of prolonged activity in selected subtypes of rare sarcomas.
Clinical trial identification
NCT03012620 EudraCT 2016-002260-14.
Editorial acknowledgement
Legal entity responsible for the study
R&D UNICANCER.
Funding
La Ligue Nationale contre le Cancer, Institut National du Cancer (INCa), MSD.
Disclosure
J. Blay: Honoraria (self), Honoraria (institution), Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Honoraria (institution), Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Honoraria (institution), Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Honoraria (institution), Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (institution): Innate. C.M. Chevreau: Advisory / Consultancy: MSD. J. Soria: Advisory / Consultancy, Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Shareholder / Stockholder / Stock options: Gritstone; Advisory / Consultancy: Astex; Advisory / Consultancy: Clovis; Advisory / Consultancy: GSK; Advisory / Consultancy: GammaMabs; Advisory / Consultancy: Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Mission Therapeutics; Advisory / Consultancy: Merus; Advisory / Consultancy: Pfizer; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Servier; Advisory / Consultancy: Symphogen; Advisory / Consultancy: Takeda. C. Massard: Advisory / Consultancy: Amgen; Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: BeiGene; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: CelGene; Advisory / Consultancy: Debiopharm; Advisory / Consultancy: Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy: Lilly; Advisory / Consultancy: MedImmune; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy: Orion; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Merck; Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: BeiGene; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: CelGene; Advisory / Consultancy: Debiopharm. All other authors have declared no conflicts of interest.
Resources from the same session
5071 - Expression of estrogen receptor and programmed cell death-ligand 1 can be complementary prognostic factors in HPV-positive oropharyngeal squamous cell carcinoma
Presenter: Soohyeon Kwon
Session: Poster Display session 3
Resources:
Abstract
5306 - Real-world data of clinicopathologic characteristics of young oropharyngeal cancer patients.
Presenter: Maria Nieva
Session: Poster Display session 3
Resources:
Abstract
3407 - The clinical significance and biological mechanisms of miR-499a in high-tobacco exposed head and neck squamous cell carcinoma
Presenter: Shiqi Gong
Session: Poster Display session 3
Resources:
Abstract
3310 - Liquid biopsy for mutational profiling of locoregional recurrent and/or metastatic squamous cell carcinoma of the head and neck
Presenter: Rachel Galot
Session: Poster Display session 3
Resources:
Abstract
2362 - Blood-based testing of mutations in patients with Head and neck squamous cell carcinoma (HNSCC) using highly sensitive SafeSEQ technology
Presenter: Florentia Fostira
Session: Poster Display session 3
Resources:
Abstract
4533 - The head and neck Lung Immune Prognostic Index (HN-LIPI): a prognostic Score for Immune Checkpoint Inhibitors (ICI) in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN) patients.
Presenter: Ruth Gabriela Herrera Gomez
Session: Poster Display session 3
Resources:
Abstract
5262 - Immune-related adverse events (irAEs) and outcome in recurrent/metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) patients (pts) treated by immune-checkpoints inhibitors (ICI)
Presenter: Neus Baste Rotllan
Session: Poster Display session 3
Resources:
Abstract
3725 - Intratumoral and peripheral exploratory biomarker analysis in patients with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC) treated with RM-1929 photoimmunotherapy
Presenter: Jack Bui
Session: Poster Display session 3
Resources:
Abstract
2533 - A nomogram based prognostic score to predict overall survival (OS) in recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients (pts) treated with immune checkpoint inhibitors (ICI).
Presenter: Luay Mousa
Session: Poster Display session 3
Resources:
Abstract
2929 - Changes of the Commensal Microbiome during Treatment are Associated with Clinical Response in the Nasopharyngeal Carcinoma Patients
Presenter: Tingting Huang
Session: Poster Display session 3
Resources:
Abstract