Abstract 4985
Background
Nivolumab is an established treatment for recurrent/metastatic (RM) head and neck squamous cell carcinoma (HNSCC) patients (pts) failing platinum-based treatment. However, knowledge about safety and activity data are limited to pts enrolled into clinical trial leading to drug approval.
Methods
We conducted a single-arm, open-label, multicentre prospective phase IIIb clinical trial with nivolumab 240 mg in subjects with RM HNSCC. Primary objective was to assess the incidence of high-grade (CTCAE v 4.03 grade 3 or higher), treatment-related (TR), selected adverse events (AE); secondary objectives were to characterize the outcome of all AE in terms of duration, time to event onset, and event resolution. Moreover, we assessed Overall Response Rate (ORR), OS and PFS and we analysed in an exploratory way clinical and biomolecular factors associated with improved outcome. A subgroup analysis was also performed in 20 pts to define baseline immunologic profiles and their changes along the treatment.
Results
We enrolled 127 pts with the following characteristics: male (82%), age higher than 65 years (43%), with primary cancer in oral cavity (33%), oropharynx (31%), larynx (24%), hypopharynx (8%) or other sites (4%). Performance status was 0 in 34% and 1 in 63% pts; 27% of the pts had received 2 or more systemic lines of therapy before. Grade 3-4 TR AE happened in 11% of the pts (anemia 2%, pneumonitis and encephalitis 1%), while all-grade TR AE were 40% (fatigue 20%, hypothyroidism 8%, anemia and pruritus 6%). Median duration of grade 3-4 TR AE was 10 days (4-22) and of grade 1-2 TR AE 63 days (1-336). Median OS and PFS were 7 months (5-NR) and 2 months (1.5-2.5) and ORR 12%. Pts experiencing any TR AE had an improved OS; HR 0.459 (0.254-0.827, p = 0.0096). Analyses of stromal tumor-infiltrating lymphocytes (TILs) status and PD-L1 status (clone 28-8 Agilent) are ongoing.
Conclusions
In this phase IIIb trial, nivolumab confirmed the safety and efficacy profile of the registration trial. Experiencing any grade TR AE revealed to be a favorable prognostic factor, as possible expression of effective immune response.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
GONO group.
Funding
Bristol Myers-Squibb.
Disclosure
P. Bossi: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy: Angelini; Advisory / Consultancy: MSD; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Voluntis. M.C. Merlano: Honoraria (self), consultancy or A.B.: Bristol M.S.; Honoraria (self), consultancy or A.B.: Merck S.D.; Honoraria (self), consultancy or A.B.: Merck; Shareholder / Stockholder / Stock options, Stocks: Glaxo SK; Research grant / Funding (institution), Support for clinical trials: Merck. M.G. Ghi: Honoraria (self), Advisory role: BMS; Honoraria (self), Advisory role: MSD; Honoraria (self), Advisory role: Merck Serono. G. Rinaldi: Honoraria (self), Research grant / Funding (self), Speaker and PI in clinical Trial: Novartis; Honoraria (self), Research grant / Funding (institution), Speaker and PI in clinical Trial: BMS; Research grant / Funding (self), PI in clinical Trial: MSD. F. Morelli: Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): BMS. A. Farnesi: Honoraria (self), speaker: Bayer; Honoraria (self), speaker: Novartis. D. Galizia: Honoraria (self), public speaker: BMS; Honoraria (self), congress travel costs coverage: Merck; Honoraria (self), congress travel costs coverage: Roche; Honoraria (self), congress travel costs coverage: Angelini. L.F. Licitra: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Speaker: BMS; Honoraria (self), Research grant / Funding (institution), Speaker: Eisai; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Speaker: MSD; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Speaker: Merck-Serono; Honoraria (self), Research grant / Funding (institution), Speaker: Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution), Speaker: Novartis; Honoraria (self), Research grant / Funding (institution), Speaker: AstraZeneca; Honoraria (self), Research grant / Funding (institution), Speaker: Roche; Honoraria (self), Travel / Accommodation / Expenses, Speaker: Bayer; Honoraria (self), Travel / Accommodation / Expenses, Speaker: Debiopharm; Honoraria (self), Travel / Accommodation / Expenses, Speaker: Sobi; Honoraria (self), For teaching in medical meetings: Incyte Biosciences Italy srl; Honoraria (self), Expert opinion in advisory board meetings: Doxa Pharma srl; Honoraria (self), For public speaking in medical meetings: Amgen; Honoraria (self), Expert opinion in advisory board meetings: Nanobiotics Sa; Honoraria (self), For public speaking in medical meetings and/or expert opinion in advisory boards: GSK; Research grant / Funding (institution), Founds to my Institution for a clinical trial (2016-2017): Celgene International; Research grant / Funding (institution), Founds to my Institution for 2 clinical trials (2014-2018): Exelixis Inc.; Research grant / Funding (institution), Founds to my Institution for a clinical trial (2014-2015): Hoffmann-La Roche Ltd.; Research grant / Funding (institution), Founds to my Institution for a clinical trial (2017): IRX Therapeutics, Inc.; Research grant / Funding (institution), Founds to my Institution for a clinical trial (2016): Medpace Inc.; Research grant / Funding (institution), Founds to my Institution for a clinical trial (2014): Pfizer; Travel / Accommodation / Expenses, Travel coverage for medical meetings: Stilema, AccMed, Aiocc, Aiom. All other authors have declared no conflicts of interest.
Resources from the same session
5007 - Functional systemic CD4 immunity is required for clinical responses to PD-L1/PD-1 blockade therapy
Presenter: Miren Zuazo
Session: Poster Display session 3
Resources:
Abstract
5760 - Landscape of PD-L1 expression status in Chinese solid tumor patients.
Presenter: Yi Zhong
Session: Poster Display session 3
Resources:
Abstract
3733 - Anti-cancer and immunomodulatory effects of cobimetinib in triple negative breast cancer
Presenter: Chun-Yu Liu
Session: Poster Display session 3
Resources:
Abstract
4426 - Differential expression of immunoregulatory molecules and highly-associated cancer genes may provide novel insights into strategic trial design for therapeutics
Presenter: Jacob Adashek
Session: Poster Display session 3
Resources:
Abstract
2752 - Insights into the Tumor Immune Microenvironment using Tissue Phenomics to Drive Cancer Immunotherapy
Presenter: Martin Groher
Session: Poster Display session 3
Resources:
Abstract
5713 - Immune competent somatic mosaic model of colorectal cancer
Presenter: Stefania Napolitano
Session: Poster Display session 3
Resources:
Abstract
1898 - Genomic correlates of response to anti-PDL1 Atezolizumab in non-small-cell lung cancer OAK and POPLAR trials
Presenter: Hari Singhal
Session: Poster Display session 3
Resources:
Abstract
3246 - Erdafitinib (erda) versus available therapies in advanced urothelial cancer: A matching adjusted indirect comparison
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
3311 - High level of activity of Nivolumab anti-PD-1 immunotherapy and favorable outcome in metastatic/refractory MSI-H non-colorectal cancer: Results of the MSI cohort from the French AcSé program
Presenter: Christophe Tournigand
Session: Poster Display session 3
Resources:
Abstract
2314 - TP53 and ATM Co-mutation Predicts Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
Presenter: Yu Chen
Session: Poster Display session 3
Resources:
Abstract