Abstract 3311
Background
Microsatellite instability-high (MSI-H) is observed in a large variety of cancer types. Immune checkpoint targeted therapies against PD-1 and CTLA-4 have demonstrated significant activity in metastatic colorectal cancer (mCRC) with nivolumab +/- ipilimumab. We aimed to demonstrate a clinical benefit of nivolumab in non-CRC MSI patients.
Methods
The AcSé immunotherapy program launched by the French National Cancer Institute (INCa) and sponsored by the French network of comprehensive cancer centers (Unicancer) is a nationwide exploratory program which has allowed access to anti-PD-1 therapies outside of their current approvals. A phase II, single arm, AcSé-nivolumab trial has been conducted to investigate the efficacy and tolerance of nivolumab in patients with metastastic/refractory rare tumor types. Here we report the results of the MSI cohort. Nivolumab (240 mg IV) was administered q2w for a max of 2 years or until disease progression (PD), or toxicity. The primary endpoint was the objective response rate (ORR) assessed by RECIST v1.1 at 12 weeks.
Results
From July 2017 to October 2018, 50 pts (mean age 63 years) were included. Primary locations were endometrial adenoCa (17), gastric (10), small bowel (7), pancreas (5), biliary (4), urothelial (2), ovary (2), and breast (2). 15 patients (30%) had a Lynch syndrome. All patients were pre-treated (mean of previous lines: 1.6) and had a MSI status locally determined by IHC and/or PCR (IHC 15 pts, PCR 4, both 31). The mean number of cycles/patients was 12.9. The ORR at 12 weeks was 38% (95%CI 24.6 to 52.8) and the best ORR at any time was 42% (95%CI, 28.2 to 56.8) with median time to response of 14 weeks. CR: n = 2; PR: n = 17; SD: n = 16; DCR=74%. Median PFS was not reached with a 6-mo PFS at 58.9% (95%CI, 46.5 to 74.6). At the date of analysis, 15 patients died (PD 13, drug related death 1, other 1), with a 6-mo OS rate at 80.3% (95%CI, 69.5 to 92.8). No unexpected adverse event of nivolumab has been observed.
Conclusions
Nivolumab as monotherapy is highly active in non-colorectal MSI patients, outperforming results of classical chemotherapy in this heavily pre-treated population.
Clinical trial identification
NCT03012581, EudraCT 2016-002257-37.
Editorial acknowledgement
Legal entity responsible for the study
R&D UNICANCER.
Funding
La Ligue Nationale Contre le Cancer, Institut National du Cancer (INCa), BMS La Ligue Contre le Cancer, INCa, BMS.
Disclosure
C. Tournigand: Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (institution), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (institution), Travel / Accommodation / Expenses: BMS. E. Saada-Bouzid: Advisory / Consultancy: BMS; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck Serono. D. Pouessel: Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): A2; Speaker Bureau / Expert testimony: Ipsen; Speaker Bureau / Expert testimony: BMS. C. Le Tourneau: Advisory / Consultancy: MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Nanobiotix; Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: GSK. P. Augereau: Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca. 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. A. Marabelle: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): BMS; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Fondation MSD Avenir; Advisory / Consultancy: Oncovir; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono; Advisory / Consultancy: eTheRNA; Advisory / Consultancy, Research grant / Funding (self): Lytix pharma; Advisory / Consultancy: Kyowa Kirin Pharma; Advisory / Consultancy: Novartis, Seattle Genetics, Molecular Partners; Advisory / Consultancy: Symphogen, Bayer, Partner Therapeutics; Advisory / Consultancy: Genmab, RedX pharma, OSE Immunotherapeutics; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen, Sanofi, Servier; Advisory / Consultancy: Biothera, Gritstone; Advisory / Consultancy: Nektar, Pierre Fabre; Advisory / Consultancy: GSK; Advisory / Consultancy: Oncosec; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (self): MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): AstraZeneca/MedImmune; Speaker Bureau / Expert testimony, Research grant / Funding (self): Roche/Genentech. All other authors have declared no conflicts of interest.
Resources from the same session
5383 - A pilot trial to investigate the impact of a personalised self-management lifestyle programme using mobile technology on the health and wellbeing of cancer survivors
Presenter: Mary Grace Kelly
Session: Poster Display session 3
Resources:
Abstract
5084 - The BRIGHTLIGHT national survey of the impact of specialist teenage and young adult cancer care on caregivers’ information and support needs
Presenter: Rachel Taylor
Session: Poster Display session 3
Resources:
Abstract
4328 - Life beyond cancer: Occupational health care service support in returning work experienced by cancer survivals
Presenter: Minna Nurmi
Session: Poster Display session 3
Resources:
Abstract
3337 - Investigating the factors related to primary caregivers' burden in oncology patients in Greece
Presenter: Ourania Govina
Session: Poster Display session 3
Resources:
Abstract
3387 - Factors Influencing the Level of Emotional Support from Nurses Perceived by Patients Undergoing Haematopoietic Stem Cell Transplantation in Protective Isolation
Presenter: Michela Piredda
Session: Poster Display session 3
Resources:
Abstract
935 - Progressive Muscle Relaxation and Guided Imagery Techniques and the Way of Coping of Parents of Children with Malignancies: A randomized controlled trial
Presenter: Tsitsi Theologia
Session: Poster Display session 3
Resources:
Abstract
3457 - Pharmacist and Nurse Led Melanoma Immunotherapy Clinic
Presenter: Dharmisha Chauhan
Session: Poster Display session 3
Resources:
Abstract
5160 - Measuring the impact of the Irish Cancer Society's Cancer Information Services
Presenter: Aileen McHale
Session: Poster Display session 3
Resources:
Abstract
4297 - It's Great to Talk
Presenter: Noreen Andersen
Session: Poster Display session 3
Resources:
Abstract
4444 - Impact of Burn-Out Syndrome in Oncology personnel and its improvement through specific interventions
Presenter: Inmaculada Ortega
Session: Poster Display session 3
Resources:
Abstract