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1103
Background: Epacadostat is an oral, potent, and selective inhibitor of indoleamine 2,3-dioxygenase 1, a tryptophan-catabolizing enzyme that induces immune tolerance via T-cell ...suppression and is associated with poor patient (pt) survival when overexpressed in some cancers. The ongoing, open-label, phase 1/2 (P1/2) ECHO-202/KEYNOTE-037 study is evaluating the efficacy, safety, and tolerability of epacadostat plus PD-1 inhibitor pembrolizumab (E + P) in pts with advanced/recurrent cancers. We report P1/2 study outcomes for triple-negative breast cancer (TNBC) pts and P2 outcomes for ovarian cancer (OVC; no P1) pts as of a 29OCT2016 data cutoff. Methods: Eligible pts were ≥18 years old with no prior checkpoint inhibitor treatment (tx); prior platinum/taxane tx was required for OVC pts. As part of P1 dose escalation, TNBC pts received E (300 mg BID) + P (200 mg Q3W). In P2, TNBC and OVC pts received E (100 mg BID) + P (200 mg Q3W). Response (RECIST v1.1) was assessed in evaluable pts. Safety and tolerability were assessed in pts with ≥1 dose of E + P. Results: A total of 39 pts with TNBC and 37 with OVC were enrolled. The majority of TNBC pts (56%, n = 22) and OVC pts (78%, n = 29) received ≥3 prior lines of tx. For TNBC pts, ORR (CR+PR) was 10% (n = 4; all PR) and DCR (CR+PR+SD) was 36% (n = 14; 10 SD); ORR and DCR for pts with ≤2 prior tx were 12% (n = 2) and 29% (n = 5), respectively, and for ≥3 prior tx were 9% (n = 2) and 41% (n = 9). For OVC pts, ORR was 8% (n = 3; all PR) and DCR was 35% (n = 13; 10 SD); ORR and DCR for pts with ≤2 prior tx were 13% (n = 1) and 25% (n = 2), and for ≥3 prior tx were 7% (n = 2) and 38% (n = 11). The most common TRAEs (≥15% of pts) were rash (18%), fatigue (15%), and nausea (15%) in the 39 TNBC pts, and fatigue (19%) in the 37 OVC pts. Grade ≥3 TRAEs occurred in 13% of TNBC pts (n = 5; none in > 1 pt) and 19% of OVC pts (n = 7; only rash occurred in > 1 pt n = 3). TRAEs led to discontinuation in 1 TNBC pt (grade 3 ascites) and 1 OVC pt (grade 2 arthralgia). Conclusions: E + P tx was generally well tolerated and showed antitumor activity consistent with previously reported P monotherapy in pts with advanced TNBC or OVC. Biomarker analysis is ongoing to characterize pt populations enrolled in this study. Clinical trial information: NCT02178722.
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Background: Pembro is an anti-PD-1 antibody with single agent activity in HER2– metastatic BC. I-SPY 2 is a multicenter, phase 2 platform trial which evaluates novel neoadjuvant ...therapies; the primary endpoint is pathological complete response (pCR, ypT0/Tis ypN0). We report current efficacy results, with final results at ASCO. Methods: Patients (pts) with invasive BC ≥2.5 cm by exam or ≥2 cm by imaging are assigned weekly paclitaxel x 12 (control) +/- an experimental agent, followed by doxorubicin/cyclophosphamide x 4. Combinations of hormone-receptor (HR), HER2, & MammaPrint (MP) status define the 8 signatures studied. MP low HR+ BC is excluded. Adaptive randomization is based on each arm’s Bayesian probability of superiority over control. Graduation by signature is based on an arm’s Bayesian predictive probability of a successful 1:1 randomized phase 3 trial with a pCR endpoint. We provide raw & Bayesian estimated pCR rates adjusted for covariates, time effects over the course of the trial, & serial MRI modeling for pts not yet assessed for pCR surgically. Results: 69 pts were randomized to pembro (HER2- subsets only) from Dec 2015 until it graduated in Nov 2016. 46 pts have undergone surgery (table); the other 23 have on-therapy MRI assessments. In 29 HR–/HER2– (TNBC) pts, pembro increased raw & estimated pCR rates by >50% & 40%, respectively; in 40 HR+/HER– pts, it did so by 13% and 21%. 5 pts had immune-related grade 3 adverse events (AEs); 1 hypophysitis & 4 adrenal insufficiency. 4 pts presented after completion of AC (149-179 d after starting pembro); 1 presented prior to AC (37 d after starting pembro). 7 pts had grade 1-2 thyroid abnormalities. Conclusion: Pembro added to standard therapy improved pCR rates in all HER2- BCs that meet I-SPY 2 eligibility, especially in TNBC. Immune-mediated AEs were observed; pt follow up is ongoing. Clinical trial information: NCT01042379. Table: see text
6528
Background: This study evaluated whether there were racial disparities in utilization (decomposed as change in proportion of eligible patients initiating therapy over time and time to treatment ...initiation (TTI)) to CDK4/6 inhibitors and pertuzumab since FDA approval as first line (1L) treatment for ER+/HER2- and HER2+ metastatic breast cancer (MBC), respectively. Methods: This cohort study used the nationwide Flatiron Health electronic health record-derived de-identified database. Included women were ≥18 years old, diagnosed with de novo or recurrent MBC, who received 1L therapy, and documented as non-Hispanic White (NHW) or non-Hispanic Black/African American (NHB). Two cohorts were generated for patients with ER+/HER2- MBC diagnosed 3/2015-10/2021 and HER2+ MBC diagnosed 7/2012-9/2021. We estimated temporal trends in the proportion of NHW and NHB patients receiving respective therapy using logistic regression with natural cubic splines for time trends and tested for changes in uptake over time within each group as well as differences in trends between groups. A similar model was used for TTI among treatment initiators, using linear regression models. In addition to time and race, regression models included age, ECOG performance status, insurance, Medicaid expansion status, practice type, and proportion of black patients per practice among patients who met both cohort criteria. Results: 8318 patients (NHW=7006; NHB=1312) met ER+/HER2- cohort criteria and 2321 (NHW=1915; NHB=406) met HER2+ cohort criteria. There was a significant change over time in the proportion of NHW (p<0.0001) and NHB (p<0.0001) initiating 1L CDK4/6 inhibitors (Table). Temporal trends were also significantly different between NHW and NHB (p<0.0001). Higher ECOG performance status (OR=0.85 per unit increase, 95%CI 0.80-0.90; p<0.001) and an increasing proportion of black patients seen at practice (OR=0.45, 95%CI 0.29-0.71; p<0.001) were independent predictors of lower odds of initiating CDK4/6 inhibitors. Overall, 43% NHW vs 41% NHB received pertuzumab respectively. There was no significant difference in uptake trends for pertuzumab between NHW and NHB (p=0.41). There was no significant difference in the temporal trends of TTI for either CDK4/6 inhibitors (p=0.74) or pertuzumab (p=0.84). Conclusions: Utilization of CDK4/6 inhibitors steadily increased over time, however > 25% of eligible patients did not receive the drug, and less than half of individuals who met indication for pertuzumab were prescribed it. Racial disparities were significant for oral CDK4/6 inhibitors but not for intravenous pertuzumab. Table: see text
561 Background: While breast cancer treatment is effective at eradicating primary disease, approximately 20% of patients will ultimately recur at a distant site. Recurrence has been linked to the ...presence of minimal residual disease (MRD) after treatment, which presents as circulating micrometastases and dormant tumor cells (DTCs) located primarily in the bone marrow. Radiomic features on MRI are imaging biomarkers that have been linked with lesion heterogeneity, which in turn has been associated with disease aggressiveness. Here, we examine the association between radiomic features from the primary lesion on MRI and the presence of post-treatment DTCs. Noninvasively identifying patients at high risk of MRD would facilitate optimized treatment strategies to reduce recurrence risk. Methods: Dynamic contrast-enhanced MRI data from breast cancer survivors enrolled in the SURMOUNT trial (N=104) were retrospectively analyzed. Participants with MRIs collected within 90 days of diagnosis who consented to provide a bone marrow aspirate (BMA) sample were eligible. Working with a board-certified radiologist, we successfully identified and segmented the primary lesion for N=70 patients with BMA outcomes. Using the publicly available CaPTk software, we computed 33 radiomic features for each segmented lesion based on pixel intensity, morphology, and grey level textures. To reduce the dimensionality of the feature space, we used these feature values to group the participants into clusters—termed radiomic phenotypes — via agglomerative hierarchical clustering with significance testing. Fisher’s exact test was applied to test the statistical significance of the association between radiomic phenotype and BMA outcome (± DTC). For all statistical tests, p<0.05 was considered significant. Results: Of the N=70 participants analyzed, 58 were negative and 12 were positive for DTCs present in the bone marrow. Two statistically significant radiomic phenotypes ( p<0.05) were identified that were strongly associated with BMA outcome ( p=0.0251). 11 out of 12 positive outcomes were grouped into the second radiomic phenotype (Table). Conclusions: We found a statistically significant association between DTC presence and radiomic phenotypes derived from MRI data. Given the large percentage of positive outcomes assigned to the second radiomic phenotype, the radiomic phenotypes may indicate low and high risk of MRD, respectively. Importantly, this analysis shows promise for the ability to predict MRD from noninvasive imaging features. These results motivate continued data collection to increase sample size and identify a robust set of radiomic features, which may ultimately be used as predictors in potential models of MRD risk. Table: see text
LBA1004 Background: Sacituzumab govitecan (SG) is a TROP2 antibody drug conjugate (ADC) with a topoisomerase I inhibitor payload (SN-38) approved for previously treated triple negative and hormone ...receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (MBC). Double-strand DNA breaks induced by SN-38 activate cGAS-STING, stimulating type I IFN production and T cell recruitment. SN-38 can upregulate MHC class-I and PD-L1 expression, enhance cytotoxic T cell effector functions and deplete regulatory T cells. To evaluate if SG synergizes with pembrolizumab (PD-1 inhibitor) we conducted a randomized, open-label phase 2 study comparing SG with or without pembrolizumab in HR+/HER2- MBC (NCT04448886). Methods: Eligible patients (pts) had unresectable locally advanced or metastatic HR+ (ER≥1% and/or PR≥1%), HER2- breast cancer treated with ≥1 prior endocrine therapy and 0-1 chemotherapy (CT) for MBC. Pts with brain metastases were eligible if locoregional therapy was completed and steroids discontinued ≥7 days before study therapy. Pts who received prior topoisomerase I inhibitor ADC, irinotecan or PD-1/L1 inhibitors were excluded. Pts were randomized 1:1 to Arm A SG 10 mg/kg IV (D1, D8) + pembrolizumab 200 mg IV (D1), 21-day cycle or Arm B (SG alone). The primary endpoint was progression-free survival (PFS); secondary endpoints included PFS in PD-L1+ pts (22C3 CPS ≥1), overall survival (OS), objective response rate (ORR) and toxicity (NCI CTCAE v5.0). Baseline and on-treatment biopsies were performed for correlative analyses. For this preliminary analysis, data were locked 1/12/24. Results: Between 03/2021-01/2024, 110 pts enrolled; 104 pts (52 Arm A; 52 Arm B) started study therapy and were included in the analysis. Median age was 57 yrs (range: 27-81); 102 pts (98.1%) were female. 80 pts (76.9%) received prior CDK4/6 inhibitor for MBC; 58 (55.8%) had no prior CT, 46 (44.2%) had 1 prior line of CT for MBC. At a median follow-up of 9.2 months (mo), median PFS was 8.4 mo in Arm A vs 6.2 mo in Arm B (HR 0.76, 95% CI 0.47-1.23, log-rank p=0.26); ORR 21.2% and 17.3%, respectively. OS data are immature with only 26 events to date; OS was 16.9 mo vs 17.1 mo (HR 0.65, 95% CI 0.30-1.41, log-rank p=0.28), respectively. The most frequent treatment-related toxicities (≥G2) in Arm A were neutropenia (67.3%), fatigue (36.5%), alopecia (36.5%), anemia (32.7%), leukopenia (26.9%), diarrhea (21.2%) and nausea (21.2%); in Arm B, neutropenia (59.6%), alopecia (38.5%), diarrhea (34.6%), nausea (32.7%), fatigue (32.7%) and anemia (21.2%). Conclusions: Addition of pembrolizumab to SG showed a non-significant trend toward improved PFS in unselected HR+/HER2- MBC at this preliminary time point. Final PFS and updated OS with further follow-up will be presented at the meeting. Exploratory outcome analyses by TROP2 and PD-L1 expression will be reported. Clinical trial information: NCT04448886 .
LBA501 Background: I-SPY2.2 is a multicenter phase 2 platform sequential multiple assignment randomized trial (SMART) in the neoadjuvant breast cancer setting that evaluates novel experimental ...regimens as first in a sequence (Block A) followed by standard chemo/targeted therapies (Blocks B/C) if indicated. The goal is to achieve a pCR after novel targeted agents alone or in sequence with standard therapies, with the optimal therapy assigned based on the tumor response predictive subtype (RPS). RPS incorporates expression-based immune, DNA repair deficiency (DRD), and luminal signatures with hormone receptor (HR) and HER2 status to subset patients into 6 subtypes: S1: HR+HER2-Immune-DRD-; S2: HR-HER2-Immune-DRD-; S3: HER2-Immune+; S4: HER2-Immune-DRD+; S5: HER2+/non-Luminal; S6: HER2+/Luminal. Methods: RPS S1, S2, S3, and S4 were eligible for assignment to Dato+Durva in Block A. Patients were followed by MRI during treatment (at 3, 6, and 12 weeks after start of Blocks A and B). Predicted responders by MRI and biopsy at the end of Block A or B have the option of going to surgery early; otherwise, they proceed to next treatment Block (B +/- C). Randomization to Block B includes a taxane-based regimen specific to the RPS, and options include S1: paclitaxel; S2 and S3: paclitaxel + carboplatin + pembrolizumab; S4: paclitaxel + carboplatin vs. paclitaxel + carboplatin + pembrolizumab. Patients who did not go to surgery after Block B proceeded to Block C (AC or AC + Pembrolizumab if HR-HER2-). The primary endpoint is pCR. Efficacy is evaluated within each RPS and HR+HER2- and HR-HER2- signatures. To estimate the arm's efficacy as a stand-alone therapy, we use a Bayesian covariate-adjusted model to estimate the pCR rate and compare the posterior distribution to a subtype-specific fixed threshold. This model uses pCR data when available and MRI data when pCR is not. To estimate pCR rate in the context of a multi-decision treatment regimen, we use a Bayesian model based on if and when a pCR occurred in the trial. The posterior is compared to a subtype-specific dynamic control generated from historical I-SPY data. Results: 106 patients were randomly assigned to the Dato+Durva arm between September 2022 and August 2023. The results for Dato+Durva as a stand-alone therapy are summarized in Table. After completion of Block A, 36 patients proceeded to surgery without completing Blocks B/C. Conclusions: Dato+Durva meets threshold for graduation within the RPS S3 subtype based on estimated pCR rate of 72% and warrants further investigation in a larger randomized controlled trial. Clinical trial information: NCT01042379 . Table: see text
1572
Background: In addition to being required by the Federal Policy for the Protection of Human Subjects for United States-based institutions that receive federal funding and are engaged in ...cooperative research projects, the use of a central Institutional Review Board (cIRB) has multiple benefits. Yet more advanced trial designs have unique needs and challenges that may hinder adoption of an efficient cIRB. Platform trials, which require both a master protocol and successive individual protocol amendments for each new agent, are prone to high regulatory burden that can slow trial recruitment, representing a significant workload for study personnel. Specific challenges for platform trials include high burden of new amendments and IRB review schedules staggered across sites, making it challenging to have all sites operating under the same amendment concurrently. Methods: Administrative assessments were collected over the course of the I-SPY2 trial. The primary outcome of interest was time from amendment submission to approval (calculated as the number of days from submission to the local IRB by the site investigators to approval by the local IRB). Quantitative data in terms of hours spent on regulatory tasks pre- and post-cIRB implementation was estimated. Site investigators were asked in December 2022 to complete a brief questionnaire to investigate perceptions on changes to workload and level of comfort using a cIRB. Results: Amendments were activated when 50% of high accruing sites had IRB approval. The number of sites with approval for an amendment to go live was < 25% prior to cIRB adoption, and 83% after. Following transition to the cIRB in February 2021, the mean time from amendment submission to approval decreased from 54.4 to 20.7 days by Jan 2023. Changes to the informed consent were possible once the cIRB was adopted, including: standardizing site-specific IRB language in a section of the consent, so it need not be adjusted with every new agent amendment; standardizing site-specific workflows; shortening consent and making it more patient friendly. The average time that CRCs spent on regulatory work at each site decreased by an average of 160 minutes, but was variable, revealing continued use of local IRB, other committees at some sites. A total of 14 respondents completed the survey; most respondents indicated that keeping up with the amendment approval process was easier post-cIRB and 94% were comfortable relying on a cIRB. The short time for cIRB approval revealed the inefficiency of other processes, including coverage analysis and building of drug order sets. Conclusions: Active engagement of cIRB leadership and IRB working group has enabled regulatory review that now takes less than 30 days. The cIRB is now the standard for the I-SPY family of trials. Other services can also be shared and will continue to drive efficiency and reduce the regulatory burden for sites.
510
Background: HER2-positive breast cancer (bc) is a very heterogenous disease. We hypothesized that molecular subtype may predict disease response to investigational agents in HER2+ bc. Here, we ...report the pathologic complete response (pCR) rate in the first six agents tested in HER2+ bc in the I-SPY 2 trial for the full HER2+ cohort, by molecular subtype, and by disease receptor status. Methods: Women with HER2+ tumors which were > 2.5 cm were eligible. The I-SPY2 platform trial tests novel agents given neoadjuvantly with a backbone of taxol (T) and trastuzumab (H) followed by doxorubicin and cyclophosphamide. Agents investigated in HER2+ bc were TH (control), MK2206, AMG386, pertuzumab (P), neratinib (N (given in place of H), and TDM1+P (given in place of TH). An investigational arm graduated if there was >85% chance of success compared to control in a 300-person phase 3 neoadjuvant trial. Further details of the I-SPY2 methods have been previously published. Molecular subtyping based on gene expression was utilized to categorize tumors into 5 response predictive subtypes (RPS) (HER2-/Immune-/DRD (DNA repair deficiency)-, HER2-/Immune+, HER2-/Immune-/DRD+, HER2+/Her2_or_Basal and HER2+/Luminal). Results: For the full HER2+ cohort (N=245) pCR rate was higher in all investigational arms than control (Table). By tumor receptor status, HER2+/HR- tumors (N=89) had a higher pCR rate than HER2+/HR+ tumors (N=156; 63% vs 37%, p = 0.0001). In HER2+/HR- tumors N, MK2206, P and TDM1/P graduated. In HER2+/HR+ tumors P and TDM1/P graduated. 76% (185/245) of I-SPY 2 HER2+ patients were classified as HER2+/Her2_or_Basal and 24% (60/245) were HER2+Luminal. pCR rate was significantly higher in the HER2+/Her2_or_Basal group than in the HER2+/Luminal group (57% vs 15%, p < 0.0001). All agents, except for MK2206, where numbers were small, showed greater efficacy in the HER2+/Her2_or_Basal group than in the HER2+/Luminal group. HER2+/Luminal appeared to be more sensitive to the AKT inhibitor MK2206 than to targeted HER2 agents, though numbers are small. Conclusions: pCR rates for patients with HER2+ bc treated with investigational agents, particularly dual HER2-blockade, were promising. Molecular response predictive subtype classification provides insight on how to better target therapy. The HER2+/Luminal group had low pCR rates with dual HER2-blockade but may have higher pCR rate with the addition of an AKT inhibitor and identifies a subgroup of HER2+ tumors in need of novel approaches. AKT inhibition for HER2/Luminal is being tested in I-SPY 2.2. Clinical trial information: NCT01042379. Table: see text
TPS612 Background: The TAILORx and RxPONDER trials demonstrated that RS identifies many postmenopausal pts with node-neg and node-pos BC and RS ≤25, who do not benefit from addition of ACT to ...endocrine therapy (ET). Both trials also showed that certain subsets of premenopausal pts (node-neg/high clinical risk/RS 16-20, node-neg/RS 21-25, and node-pos/RS ≤25) benefited from adding ACT to ET. Most premenopausal pts in these trials did not receive ovarian function suppression (OFS) as part of their ET regimen. Given the observed benefit from OFS in high-risk premenopausal pts with HR+/HER2- BC in the SOFT/TEXT trials, many questioned whether all or part of the observed ACT benefit in the TAILORx/RxPONDER trials may have been the result of chemotherapy-induced OFS. To address this question, we developed OFSET, a phase III, multicenter clinical trial comparing OFS+ET v ACT+OFS+ET. Methods: We hypothesize that addition of ACT to OFS+ET is superior to OFS+ET in improving invasive breast cancer-free survival (IBCFS) among premenopausal, early-stage BC pts with HR+/HER2- tumors, and a 21-gene RS between 16-25 (for pN0 pts) and 0-25 (for pN1 pts). Secondary objectives include invasive disease-free survival, overall survival, distant recurrence-free interval, breast cancer-free interval, and health-related quality of life (HRQOL). Pts must be node-neg with RS 16-20 (plus high clinical risk), or RS 21-25, or have 1-3 positive nodes with RS ≤25. Stratification is by nodal status/RS status (pN0 RS 16-25 v pN1 RS 0-15 and pN1 RS 16-25), intent to receive CDK4/6 inhibitor (yes; no), and age (18-39 v ≥40). Pts are randomized after surgery to either OFS+ET or ACT+OFS+ET. ET is an aromatase inhibitor (AI). Choice is per investigator discretion; tamoxifen is allowed if AI is not tolerated or if OFS is incomplete. Radiotherapy will be administered per investigator discretion per protocol guidelines. The HRQOL substudy will assess differences in severe menopausal symptoms, measured by the FACT ESS-19 score between arms, as well as increased pain severity (PROMIS). Blood and tumor specimens will be collected for future research. Accrual of 3,960 pts is anticipated to be completed in 7 yrs, 7 mos. Per NSABP B-28 and RxPONDER data, 5yr IBCFS of pN1 pts on the ACT+OFS+ET arm is estimated at 92.3%. Based on TAILORx data, 5yr IBCFS of pN0 pts on the ACT arm is ~95%. Assuming 56% of pts to be pN0 and 44% pN1, and a 0.5% annual loss-to-follow-up rate, the definitive analyses to detect a hazard ratio: 0.75 with ACT+OFS+ET v OFS+ET, with one-sided α of 0.025 and 80% power, will require 380 IBCFS events, expected to occur~11 yrs after study initiation. OFSET was activated Aug 2023. Clinical trial information: NCT05879926 .
1037 Background: TBCRC041, a randomized phase 2 trial of alisertib (A) ± fulvestrant (F) in women with HR+/HER2- MBC demonstrated promising clinical activity for alisertib (1). Interrogation of ...baseline (PreC1) and end of cycle 1 (EOC1) cfDNA and CTCs may identify biomarkers associated with response to A±F. Methods: Plasma cfDNA was sequenced using the Guardant INFINITY platform, which includes genomic and methylated tumor fraction (mTF) analysis. Pathogenic variants were determined using publicly available databases and Mayo Clinic annotation pipelines. CTCs were identified as nucleated, EpCAM+/ cytokeratin+/ CD45- cells and assessed for ER/HER2 staining (RareCyte, Seattle). PFS was defined as the time from randomization to progression or death. EOC1-PFS differs from PFS as time starts at C2D1. Stratified log-rank tests and conditional Cox modeling were used to assess whether PFS or EOC1-PFS differed by mutations in ESR1 or PIK3CA, pre-CTC ≥ 5, or mTF>1%. Results: Of the 91 eligible pts, 84 progressed, and 73 were deceased. In the 86 pts with PreC1-cfDNA results, variants were identified in ESR1 (42; 48.8%), PIK3CA (36; 41.9%), AKT1 (7; 8.1%), PTEN(7; 8.1%), BRCA1 (4; 4.7%), and BRCA2 (7; 8.1%). Pts with a PIK3CAmut had significantly decreased PFS (HR 1.8; 95%CI: 1.1 -2.9, p=0.014) but not by ESR1mut status (p=0.583). PreC1 and EOC1-mTF were determined for 78 and 76 pts, respectively. PreC1-mTF was 0-1% in 21; 1.1-10.0% in 27; and 10.1-100% in 30. mTF levels remained between 0-1% in 17 pts fell to 0-1% in 11 pts, and was 0-1% in 5 pts without a preC1-mTF determination. PFS did not differ with respect to PreC1-mTF (p=0.210), but EOC1-PFS was worse in pts with mTF >1% (HR 3.0; 95%CI: 1.6 -5.2, p<0.001). PreC1 and EOC1-CTC were determined for 78 and 76 pts. 36 (46.2%) pts had a PreC1 CTC count ≥ 5. EOC1-CTC levels remained at (n=17) or increased to (n=1) ≥ 5 and was ≥ 5 in 2 pts without a preC1-CTC determination. EOC1-PFS was not significantly different for EOC1-CTC ≥ 5 (p=0.065), but was significantly decreased in pts with PreC1-CTC≥5 (HR=1.8; 95%CI: 1.1-3.0; p=0.018). Broader cfDNA NGS panel and CTC-derived ER/HER2 staining results will be presented at the meeting. Conclusions: Among patients receiving A±F, PFS varied based on the PIK3CAmutation status. cfDNA and CTC assessment PreC1 and EOC1 provided complementary information. Further validation in larger datasets is needed. 1. JAMA Oncol 2023;9:815. Clinical trial information: NCT02860000 .
