Abstract 421P
Background
Tumors deficient in DNA repair mechanism, particularly the HRR including BRCA (somatic and /or germline ) are sensitive to Platinum chemotherapy, PARP inhibitors (PARPi), and immunotherapy (IO) in cancers like breast and ovarian, however, clinical trials are ongoing in pancreatic, prostate, endometrial and other cancer types which have progressed on first-line chemotherapy. In this study, CGP identified the landscape of sBRCA and HRR as potential biomarkers across the multi-cancer cohort.
Methods
950 biopsy proven patient samples at HCG were profiled using Illumina TruSight Oncology 500 assay on NextSeq2000 in an IRB-approved study. Sequenced data was processed by StrandOmics platform.
Results
About 142 (15 %) patients in the studied cohort of multiple cancer types were found with alterations in sBRCA and HRR pathway. 208 mutations were detected across 950 cases with 66 cases reporting ≥ 1 HRR gene alterations (mean incidence of 1.4/case). 37 HRR cases were associated with elevated tumor mutation burden. sBRCA1 and sBRCA2 were found in 22 and 27 patients respectively accounting for 3% HRR pathway. Other HRR genes included ATM, RAD51, PTEN, ATRX, PALB2, MRE11A, RAD50, CDK12, ARID1A and PTEN in 12 % of HRR pathway. It is noteworthy that sBRCA and HRR gene alterations were found across diverse cancers, highest in gastrointestinal followed by breast cancer (TNBC-56%) (Table). Apart from FDA approved cancers (n=57), HRR alteration were prevalent across other diverse cancers (n=85) in the cohort. 60% patients with sBRCA and HRR mutations treated with platinum / PARPi as NACT, achieved partial to pathological complete response (pCR) while 5 cases treated with IO are on follow up. Table: 421P
Prevalence of sBRCA and HRR genes across the multi-cancer cohort of 950 cases
Cancer | N=142 HRR+ve cases (%) | Major HRR alterations |
Gastrointestinal | 33 (23%) | ATM, ARID1A, BRCA1, PTEN, MRE11 |
Breast | 23 (16%) | BRCA1, PTEN, PALB2, ARID1A, ATM |
Triple-negative breast cancer (TNBC) | 13 (56% of Breast cancer cases with HRR alterations) | BRCA1, BRCA2, PTEN, BAP1, PALB2 |
Female genital tract | 20 (14%) | BRCA1, ARID1A, PTEN, RAD54L |
Lung | 19 (13%) | PTEN, ATM, BRCA1, ARID1A |
Head & neck | 13 (9%) | PTEN, ARID1A, ATM, BARD1, RAD50 |
Sarcoma | 10 (7%) | ATRX, PTEN, BRCA2, PALB2 |
Genitourinary | 10 (7%) | CDK12, BRCA1, PTEN |
Other cancers | 9 (6%) | PTEN, ARID1A, BAP1, RAD50 |
Carcinoma of unknown origin | 5 (4%) | ARID1A, ATRX, PTEN |
Conclusions
CGP identified sBRCA and HRR mutations in wide spectrum of cancers enabling the utility of PARPi as maintenance therapy, hence necessitating sBRCA and HRR testing as standard of care besides germline testing for personalized therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
B.S. Ajaikumar: Financial Interests, Institutional, Member of Board of Directors, Executive Chairman: HCG. All other authors have declared no conflicts of interest.
Resources from the same session
519P - Final results and subgroup analysis of ORIENTAL: A phase IIIB study of durvalumab plus platinum-etoposide in first-line treatment of Chinese patients with extensive-stage small-cell lung cancer (ES-SCLC)
Presenter: Ying Cheng
Session: Poster Display
Resources:
Abstract
520P - Role of atezolizumab in controlling CNS progression in ES-SCLC
Presenter: Yoon Namgung
Session: Poster Display
Resources:
Abstract
521P - Camrelizumab combined with chemotherapy and apatinib as first-line therapy for extensive-stage small cell lung cancer: A phase II, single-arm, exploratory research
Presenter: Yanbin Zhao
Session: Poster Display
Resources:
Abstract
522P - Durvalumab plus etoposide and carboplatin for extensive-stage small cell lung cancer with mild idiopathic interstitial pneumonia
Presenter: Ichiro Nakachi
Session: Poster Display
Resources:
Abstract
523P - Camrelizumab plus apatinib as maintenance treatment in patients with extensive-stage small cell lung cancer who were responding or stable after standard first-line chemotherapy (CAMERA): Results from a single-arm, phase II trial
Presenter: Qi Wang
Session: Poster Display
Resources:
Abstract
524P - Treatment pattern and overall survival by lines of therapy among patients with advanced small cell lung cancer in Taiwan
Presenter: Kelly Huang
Session: Poster Display
Resources:
Abstract
525P - Development of diagnostic prediction score for malignant pleural effusion in lung cancer: MPE-Lung score
Presenter: Chaichana Chantharakhit
Session: Poster Display
Resources:
Abstract
526P - Burden and trends of tracheal, bronchus, and lung (TBL) cancer in Southeast Asia, East Asia, and Oceania from 1990-2019, and its projection of deaths to 2040: A benchmarking analysis
Presenter: Monika Chhayani
Session: Poster Display
Resources:
Abstract
527P - Efficacy of intraventricular chemotherapy with pemetrexed for leptomeningeal metastasis from lung adenocarcinoma: A retrospective study
Presenter: Fang Cun
Session: Poster Display
Resources:
Abstract
528P - Socioeconomic determinants of access to standard-of-care treatments in advanced and metastatic NSCLC in Hong Kong: A territory-wide study
Presenter: Ka Man Cheung
Session: Poster Display
Resources:
Abstract