<p>Supplementary Tables S1-S7. This is a multi-"tabbed" Excel file containing the supplementary data of the manuscript and includes a "Summary" tab with descriptions/captions for the enclosed data sheets. They are as follows: Supplementary Table S1: 800-gene Ovarian Cancer Biomarker Nanostring Panel content Supplementary Table S2: Fourteen differentially expressed genes between Plat-R primary vs Plat-S primary tumors (discovery dataset) Supplementary Table S3: Sixty five differentially expressed genes between Plat-R recurrent vs Plat-R primary tumors (discovery dataset) Supplementary Table S4: TP53 mutation status in 32 Plat-R and 26 Plat-S primary tumors (discovery dataset) Supplementary Table S5: CNV analysis on 35 cancer genes in 32 Plat-R and 26 Plat-S primary tumors (discovery dataset) Supplementary Table S6: Demographics summary of ICON7 chemo-treatment arm (biomarker population vs. ITT) Supplementary Table S7: Ten differentially expressed genes between Plat-R primary vs Plat-S primary tumors (ICON7 dataset)</p>
NeoSphere showed significantly higher pathologic complete response (pCR) with neoadjuvant pertuzumab, trastuzumab, and docetaxel compared with trastuzumab plus docetaxel, pertuzumab plus trastuzumab, or pertuzumab plus docetaxel. We assessed associations between human epidermal growth factor receptor 2 (HER2) pathway-related biomarkers and clinical outcome in response to these regimens. Tumor, serum, and whole blood samples were collected at baseline and post neoadjuvant treatment before surgery. Associations between biomarkers and pCR, and between biomarkers and clinical variables were assessed in the overall and estrogen receptor (ER)-positive and ER-negative populations. Changes in serum marker levels between baseline and post-neoadjuvant treatment were examined. No markers were associated with pCR across all groups; however, significant associations were observed for two markers in individual groups. High HER2 was significantly associated with higher pCR rates (P = 0.001) and a significant treatment interaction (P = 0.0236) with pertuzumab, trastuzumab, and docetaxel (odds ratio 2.07, P = 0.01). Low serum transforming growth factor alpha (TGFα) was associated with higher pCR rates with pertuzumab plus trastuzumab (P = 0.04) without a significant treatment interaction. Presence of truncated HER2 did not affect pCR. A non-significant decreased pCR benefit was observed consistently across groups in patients with mutated PIK3CA while the treatment benefit from pertuzumab was maintained when comparing the trastuzumab plus docetaxel and pertuzumab, trastuzumab, and docetaxel groups. Notably, PIK3CA exon 9 mutations were associated with residual disease (pooled groups), which was not found for exon 20 mutations. Serum HER2 extracellular domain levels were significantly increased between baseline and post-neoadjuvant treatment in the non-trastuzumab-treated group, and decreased in the trastuzumab-containing groups (likely due to trastuzumab's mechanism of action). Differences in biomarker profiles according to ER status were observed. The observed associations of HER2 protein levels with sensitivity to pertuzumab, and of PIK3CA exon 9 mutation to lack of sensitivity to HER2-targeted monoclonal antibody treatment, warrant further investigation. Previously reported findings of truncated forms of HER2 as resistance markers to HER2-targeted treatment could not be confirmed in NeoSphere. Conventional HER2 assessment should continue and HER2 remains the only biomarker suitable for patient selection in this population. Clinicaltrials.gov, NCT00545688 . Registered on 16 October 2007.
<p>Table S1. Overlap of biomarkers measured in OAM4558g; Table S2. Primer/probe information; Table S3. MET diagnostic scoring criteria; Table S4. MET IHC intratumoral heterogeneity; Table S5. Impact of KRAS/EGFR mutation on clinical outcome; Table S6. Biomarker status in EGFR-mutant patients; Table S7. Association of transcript expression with PFS in OAM4558g.</p>
Supplementary Table S2 from Predictive Biomarkers of Sensitivity to the Phosphatidylinositol 3′ Kinase Inhibitor GDC-0941 in Breast Cancer Preclinical Models
