Abstract 1911
Background
The anticipated approval of the first specific PIK3CA inhibitor, apelisib, has increased interest in the frequency and range of PIK3CA genomic alterations (GA) in the major subtypes of mBC.
Methods
DNA was extracted from 3,871 mBC: 1,259 ER+/HER2-, 1,969 HER2 amplified (amp) and 643 TNBC. GA, tumor mutational burden (TMB) and microsatellite instability (MSI) were identified by hybrid-capture. PD-L1 was determined by IHC.
Results
PIK3CA GA were significantly higher in ER + (39%) and HER2amp (37%) and lower in TNBC (21%) groups and dominated by point mutations and indels (mut) (Table). The H1047R was the most frequent PIK3CA GA in all groups. ESR1 GA were highest in ER+ and BRCA1 GA were most frequent in PIK3CAmut- TNBC and BRCA2 GA were most frequent in PIK3CAmut- ER+. FGFR1 GA were significantly more frequent in PIK3CAmut- ER+ and EGFR and BRAF GA were most frequent in PIK3CAmut+ TNBC. Biomarkers of potential immunotherapy benefit including CD274amp and PD-L1 expression in immunocytes were most frequent in the TNBC patients, while TMB was highest in the PIK3CAmut+ cohort, regardless of subtype.Table:
306PD
| ER+/HER2- (1,249) | HER2 Amp (1,922) | TNBC (925) | ||||
|---|---|---|---|---|---|---|
| PIK3CAmut+ | PIK3CAmut- | PIK3CAmut+ | PIK3CAmut- | PIK3CAmut+ | PIK3CAmut- | |
| 481 (39%) CN 4% Mut 96% H1047R 30% E545K 17% E542K 15% N345K 5% | 768 (61%) | 715 (37%) CN 8% Mut 92% H1047R 34% E545K 15% E542K 10% N345K 3% | 1,207 (63%) | 192 (21%) CN 17% Mut 83% H1047R 30% E545K 8% E542K 7% N345K 3% | 733 (79%) | |
| Age (range in years) | 57 (23-89+) | 53 (22-89) | 55 (25-88) | 53 (20-89+) | 56.5 (30-89+) | 53 (20-89+) |
| PIK3CA GA | 100% | 0% | 100% | 0% | 100% | 0% |
| TP53 GA | 39% | 47% | 75% | 68% | 74% | 88% |
| PTEN GA | 9% | 12% | 3% | 6% | 15% | 15% |
| CDH1 GA | 11% | 5% | 5% | 3% | 9% | 3% |
| ESR1 GA | 16% | 16% | 7% | 6% | 2% | <1% |
| BRCA1/2 GA | 1%/3% | 4%/7% | 1%/2% | 3%/3% | 3%/3% | 8%/4% |
| HER2 amp | 0% | 0% | 100% | 100% | 0% | 0% |
| HER2 mut | 2% | 3% | 7% | 6% | 5% | 2% |
| Other Kinase GA | FGFR1 14% EGFR 1% BRAF 1% | FGFR1 21% EGFR 2% BRAF 2% | FGFR1 11% EGFR 3% BRAF 1% | FGFR1 11% EGFR 3% BRAF 1% | FGFR1 9% EGFR 11% BRAF 3% | FGFR1 8% EGFR 3% BRAF 3% |
| AR amp | <1% | <1% | 2% | 1% | 3% | <1% |
| MSI High | <1% | <1% | <1% | <1% | 0% | <1% |
| CD274 (PD-L1) amp | <1% | 1% | 1% | 1% | 3% | 3% |
| TMB > 10/20 mut/Mb | 11%/5% | 5%/1% | 11%/3% | 8%/1% | 11%/3% | 6%/1% |
| PD-L1 TILs low/high | 9%/0% n = 33 | 11%/0% n = 57 | 11%/0% n = 45 | 9%/0% n = 79 | 20%/0% n = 15 | 17%/1% n = 75 |
Conclusions
A wide variety of PIK3CA GA are identified in mBC and appear to influence other important biomarkers such as BRCA1/2 GA and TMB status. The PIK3CA GA distribute differently among the ER+, HER2+ and TNBC cohorts and may impact the initial and future use of PIK3CA inhibitors in the treatment of the disease.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Foundation Medicine.
Funding
Foundation Medicine.
Disclosure
E.S. Sokol: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. L.A. Albacker: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J.A. Elvin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J. Vergilio: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J..K. Killian: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. N. Ngo: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. D. Lin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. S. Ramkissoon: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. E. Severson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. S.M. Ali: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. A.B. Schrock: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J. Chung: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. P. Reddy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. V.A. Miller: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. B.M. Alexander: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Foundation Medicine. K. McGregor: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. J.S. Ross: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine. All other authors have declared no conflicts of interest.
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