Table 1.
Demographic and baseline disease characteristics of the patientsa
| Characteristic | Olaparib (n = 921) | Placebo (n = 915) |
|---|---|---|
| Age, median (interquartile range), years | 42 (36–49) | 43 (36–50) |
| gBRCA P/LP genedn (%)b | ||
| BRCA1 | 656 (71.2) | 669 (73.1) |
| BRCA2 | 260 (28.2) | 238 (26.0) |
| BRCA1 and BRCA2 | 2 (0.2) | 5 (0.5) |
| No gBRCA P/LP variant | 2 (0.2) | 3 (0.3) |
| Missing | 1 (0.1) | 0 (0.0) |
| Prior adjuvant/neoadjuvant chemotherapy, n (%) | ||
| Adjuvant | 461 (50.1) | 455 (49.7) |
| Neoadjuvant | 460 (49.9) | 460 (50.3) |
| Anthracycline and taxane regimen | 871 (94.6) | 849 (92.8) |
| Anthracycline regimen (without taxane) | 7 (0.8) | 13 (1.4) |
| Taxane regimen (without anthracycline) | 43 (4.7) | 52 (5.7) |
| Regimen not reported | 0 (0.0) | 1 (0.1) |
| <6 cycles of (neo)adjuvant chemotherapy | 7 (0.8) | 13 (1.4) |
| Platinum-based (neo)adjuvant therapy | ||
| No | 674 (73.2) | 677 (74.0) |
| Yes | 247 (26.8) | 238 (26.0) |
| Concurrent hormone therapy (hormone receptor positive only), n (%) | 146/168 (86.9) | 146/157 (93.0) |
| Hormone receptor status, n (%)c | ||
| Hormone receptor positive/HER2 negatived | 168 (18.2) | 157 (17.2) |
| Triple-negative breast cancere | 751 (81.5) | 758 (82.8) |
| Menopausal status (females only), n (%) | ||
| Premenopausal | 572/919 (62.2) | 553/911 (60.7) |
| Postmenopausal | 347/919 (37.8) | 358/911 (39.3) |
| Primary breast cancer surgery, n (%) | ||
| Mastectomy | 699 (75.9) | 674 (73.7) |
| Conservative surgery only | 222 (24.1) | 239 (26.1) |
| Missing | 0 (0.0) | 2 (0.2) |
HER2, human epidermal growth factor receptor 2; P/LP, pathogenic or likely pathogenic variants
Further information on baseline characteristics is provided in Supplementary Table S2, available at https://doi.org/10.1016/j.annonc.2022.09.159. Percentages may not total 100 because of rounding.
For a detailed description of local and central Myriad BRCA testing in patients enrolled in the trial, see Supplementary Figure S2, available at https://doi.org/10.1016/j.annonc.2022.09.159. Variant interpretation by Myriad Genetics (BRCAnalysis) (1649 patients) and BGI Genomics (247 patients) was carried out with the use of multiple established databases (e.g. ClinVar, ClinGen, and ENIGMA) and published and internal functional and clinical data, compliant with American College of Medical Genetics published guidelines. Eighty-five patients randomized in China had variant interpretation by both BGI Genomics and Myriad Genetics. The 24 pathogenic or likely pathogenic variants from local laboratories without central Myriad confirmation were confirmed by the OlympiA genetics advisory committee with the use of published databases as above. Discordant data are referred to in Supplementary Figure S2, available at https://doi.org/10.1016/j.annonc.2022.09.159. Listing of pathogenic or likely pathogenic BRCA1 and BRCA2 variants that occurred in more than one patient have previously been reported.12
Hormone receptor status was defined by local test results.
The original protocol that was activated in 2014 was developed for HER2-negative patients but included only patients with triple-negative breast cancer after regulatory review. When the safety rationale with respect to recurrence risk relative to combination therapy with olaparib and endocrine therapy was accepted by regulators, the protocol was amended in 2015 to include patients with high-risk hormone receptor-positive disease and to increase the sample size to the current number of 1800 patients (see the protocol). The first patient with hormone receptor-positive disease was enrolled in December 2015.
Triple-negative breast cancer was defined in the eligibility criteria as estrogen receptor negative and progesterone receptor negative, as indicated by immunohistochemical (IHC) nuclear staining of <1%, and HER2 negative (not eligible for anti-HER2 therapy), as indicated by one of the following: an IHC score of 0 or 1+; an IHC score of 2+ and HER2-nonamplified disease on in situ hybridization (ISH) with a ratio of <2.0 and, if reported, an average HER2 copy number of <4 signals per cell; or HER2-nonamplified disease on ISH with a ratio of <2.0 and, if reported, an average HER2 copy number of <4 signals per cell (without IHC). Two patients (both in the olaparib group) were excluded from the summary of the subgroup with triple-negative breast cancer because they did not have confirmed HER2-negative status.