Abstract 4836
Background
Lung cancer patients with activating EGFR mutations tend to respond poorly to IO, but this is not true for all activating mutation driven lung cancers. Recent data show that patients with BRAF mutations tend to respond better to IO. Our study estimated the tumor neoantigen burden in these tumors, and the likelihood of their presentation to cytotoxic T cells by estimating their binding affinity to major histocompatibility complex (MHC).
Methods
Whole exome data for 68 patients with EGFR mutant lung adenocarcinoma and 33 with BRAF mutations were extracted from the Cancer Genome Atlas. MAFTOOLs was used to determine the tumor mutational load. Nonamers were estimated by simulating possible nonamer neoantigens from MAF files. The neoantigen (MT) and wildtype (WT) binding affinities to MHC-I were calculated using the NetMHC 4.0 server. The differential binding affinity of the neoantigens in comparison to wildtype was calculated as mean differential agretopicity index (DAI) = WT - MT. Patient survival was estimated by the Kaplan-Meier method.
Results
Patients with mutated BRAF had higher median mutational burden (445, range 165-776) than those with EGFR mutations (90.5, range 60.5-219.5, p = 0.001). The median number of simulated neoantigens was higher in the BRAF (9536.5, range 3839.5-14626.0) vs the EGFR group (1895.5, range 1148.5-4766.5, p < 0.001). Mean DAI for BRAF and EGFR patients were 1046 and 1033, respectively, p = 0.86. In the BRAF mutant group, patients with DAI < 1,000 had significantly better 5-year survival (80% vs 40%, p = 0.022) compared to patients with DAI > 1,000. No such survival benefit was identified in the EGFR mutant group (56% vs 58%, p = 0.81).
Conclusions
BRAF mutant lung cancers are characterized by higher neoantigen burden, but their neoantigen differential binding affinity to MHC-I complex was not different from EGFR mutant lung cancers. Our analysis suggests that the improved response to IO in the BRAF mutant population is due to increased quantity in neoantigen burden and not a qualitative difference in MHC-I binding. Further, DAI had a prognostic impact in the BRAF population suggesting that it may be a measure of tumor neoantigen immunogenicity.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J. Subramanian: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Paradigm; Speaker Bureau / Expert testimony: Lilly; Research grant / Funding (institution): Biocept. All other authors have declared no conflicts of interest.
Resources from the same session
3361 - Providing a nurse-led telephone intervention for patients treated with oral anticancer medication: symptom management and adherence monitoring
Presenter: Etienne Minvielle
Session: Poster Display session 3
Resources:
Abstract
3937 - Chronological evaluation of health-related quality of life and physical symptoms in postoperative pancreatic cancer patients up to 12 months
Presenter: Naoko Sato
Session: Poster Display session 3
Resources:
Abstract
5620 - Understanding the patients’ Experiences of Radiation Therapy: A Qualitative Study on Prostate Cancer Patients
Presenter: Sakarias Johansson
Session: Poster Display session 3
Resources:
Abstract
1792 - Effect of Kegel exercises on prevention of urinary and fecal incontinence in patients with prostate cancer undergoing radiotherapy
Presenter: Aydan Uravylioglu
Session: Poster Display session 3
Resources:
Abstract
2169 - The Meaning of Responsibility – a Secondary Analysis of Patients and Caregivers Calls to an Oncology Emergency Telephone
Presenter: Heidi Jacobsen
Session: Poster Display session 3
Resources:
Abstract
4587 - Cognitive function changes and Associated Factors in Patients Receiving Chemotherapy
Presenter: Elif Dil
Session: Poster Display session 3
Resources:
Abstract
1981 - Prevention of dental complications in patients with multiple myeloma (MM) receiving bisphosphonates treatment
Presenter: CESCA PUIGMARTI
Session: Poster Display session 3
Resources:
Abstract
2725 - Safety profile of oral netupitant/palonosetron in hematopoietic stem cell transplantation recipients.
Presenter: Marina Bosch - Damas
Session: Poster Display session 3
Resources:
Abstract
5112 - Symptomatic and toxicity management of cancer patients using a telephone support model led by the oncology nurse
Presenter: Gemma Simó
Session: Poster Display session 3
Resources:
Abstract
1365 - Symptom cluster of fatigue, sleep disturbance and depression and its impact on quality of life among Chinese breast cancer patients undergoing adjuvant chemotherapy: A cross-sectional study
Presenter: Xiaole HE
Session: Poster Display session 3
Resources:
Abstract