Abstract GS3-07: Clinical utility of circulating tumor cell count as a tool to chose between first line hormone therapy and chemotherapy for ER+ HER2- metastatic breast cancer: Results of the phase III STIC CTC trial

Abstract

Background: In ER+ HER2- metastatic breast cancer (MBC) patients, the clinical choice between 1st line hormone therapy (HT, the recommended option) or chemotherapy (CT) is based on the absence of “visceral crisis” or adverse prognostic factors, with no proven/objective criteria. In that context, STIC CTC (NCT01710605) was set up as a strategy trial to test whether circulating tumor cells (CTC) count could help customize the choice between 1st line HT or CT. Methods: For this multicenter phase 3 non-inferiority trial, the main inclusion criteria were: ER+ HER2- MBC with no prior therapy, PS≤2, no contra-indication to HT or CT and informed consent. The a priori treatment choice (HT or CT) and CTC count (CellSearch®) were obtained in all patients prior to randomization. Patients were randomized 1:1 between clinically-driven choice (CTC count not disclosed, HT or CT administered as decided a priori), or a CTC-driven choice (HT if <5 CTC/7.5ml, CT if ≥5 CTC/7.5ml). The primary objective was treatment efficacy (PFS hazard ratio), non-inferiority being established if the upper bound of the PFS HR 2-sided 90%CI is ≤1.25; secondary objectives included subgroup analyses (CTC status, patient characteristics) and OS. Results: 761 MBC patients were randomized between 02/2012 and 08/2016. Baseline characteristics: 7.8% of patients had a PS=2, 24.1% had a de novo metastatic disease; 63.3% received prior adjuvant HT and 49.9% prior adjuvant CT; 31.3% had ≥3 metastatic sites. A priori treatments (HT or CT) and CTC count (< or ≥5 CTC/7.5ml) were well balanced between the two arms. After randomization, in the clinically-driven arm, N=267 (72.4%) patients received HT and N=102 (27.6%) CT (as decided a priori). In the CTC-driven arm: (1) the a priori choice of HT was confirmed by a low CTC count in N=181 (67.5%) of patients, while N=87 (32.5%) were switched to CT due to a high CTC count; (2) the a priori choice of CT was confirmed by high CTC count in only N=48 (48%) patients, while N=52 (52%) were switched to HT. The primary endpoint was met, PFS being not inferior in the CTC-driven arm (HR=0.98, 90%CI=[0.84–1.13]). Analyses focusing on discordant subgroups showed that for patients with a priori choice of HT but with high CTC count (leading to a switch to CT in the CTC-arm), PFS was significantly longer in the CTC-driven arm than in the standard arm (HR=0.67, 95%CI=[0.49–0.92]; p=0.01), with a non-significant trend toward longer OS (HR=0.68, 95%CI=[0.44–1.07]; p=0.09). Inversely, for patients with a priori choice of CT but with low CTC count (i.e. de-escalation to HT in the CTC arm), PFS was not statistically different between the two arms. Conclusion: This trial demonstrates the clinical utility of CTC count as an objective decision tool when considering 1st line therapy in ER+ HER2- MBC. In most patients, CTC count did confirm the a priori clinical choice; however, trial results show that in discrepant cases, CTC count may be trusted for either escalating (i.e. considering CT in patients if high CTC count) or de-escalating (i.e. considering HT in patients if low CTC count) 1st line therapy. Funding: French National Cancer Institute; Menarini Silicon Biosystems. Citation Format: Bidard F-C, Jacot W, Dureau S, Brain E, Bachelot T, Bourgeois H, Goncalves A, Ladoire S, Naman H, Dalenc F, Gligorov J, Espie M, Levy C, Ferrero J-M, Loirat D, Cottu P, Dieras V, Simondi C, Berger F, Alix-Panabieres C, Pierga J-Y. Clinical utility of circulating tumor cell count as a tool to chose between first line hormone therapy and chemotherapy for ER+ HER2- metastatic breast cancer: Results of the phase III STIC CTC trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS3-07.

Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

“…Currently, numerous clinical trials are addressing this issue, most (41%) in the USA, 12% in China, 10% in Germany and 9% in France [93]. In some of the trials, CTC are only enumerated [94,95] whereas other also asses their phenotype [96,97]. They are attempting to answer the question if either CTC number or/and CTC phenotype may serve as a criterion for therapy decisions.…”

“…The second completed trial is a STI-CTC III phase study from French group [94]. This study was set up as a strategy trial to test whether CTC count could help customize the choice between first-line hormone therapy (HT) or chemotherapy (CT) in ER+ HER2-MBC patients.…”

Update Mammakarzinom 2019 Teil 2 – Implementierung neuer Diagnostika und Therapien bei Patientinnen mit fortgeschrittenem Brustkrebs in der klinischen Praxis

“…Bei Patientinnen mit metastasiertem Mammakarzinom ist der Nachweis von mindestens 5 zirkulierenden Tumorzellen (CTC) im peripheren Venenblut ein negativer prognostischer Faktor [64]. Bidard et al stellten daher die Frage, ob der Nachweis von CTCs (mindestens 5 CTCs/7,5 ml Blut mittels CellSearch, Menarini Silicon Biosystems, Castel Maggiore BO, Italien) bei Patientinnen mit hormonrezeptorpositivem, HER2-negativem Mammakarzinom im fortgeschrittenen Stadium als Entscheidungskriterium herangezogen werden kann, ob eine endokrine Therapie (ET) ausreichend oder eine Chemotherapie mit anschließender endokriner Therapie (CTX) notwendig ist[65]. Hierfür wurden 761 Patientinnen in die prospektiv randomisierte Phase-III-STIC-CTC-Studie eingeschlossen.…”

“…Hier war der CTC-Arm dem Kontrollarm nicht unterlegen. In einer geplanten Subgruppenanalyse zeigte sich zudem, dass Patientinnen mit ≥ 5 CTCs auch dann von einer Chemotherapie profitieren, wenn von klinischer Seite eine endokrine Therapie als ausreichend ange-sehen wurde[65]. Die Autoren kommen daher zu dem Schluss, dass CTCs als Marker für die Anwendung einer Chemotherapie herangezogen werden könnten.…”

Update Mammakarzinom 2019 Teil 2 – Implementierung neuer Diagnostika und Therapien bei Patientinnen mit fortgeschrittenem Brustkrebs in der klinischen Praxis

“…B. NCT01545648).Bei Patientinnen mit metastasiertem Mammakarzinom ist der Nachweis von mindestens 5 zirkulierenden Tumorzellen (CTC) im peripheren Venenblut ein negativer prognostischer Faktor[64]. Bidard et al stellten daher die Frage, ob der Nachweis von CTCs (mindestens 5 CTCs/7,5 ml Blut mittels CellSearch, Menarini Silicon Biosystems, Castel Maggiore BO, Italien) bei Patientinnen mit hormonrezeptorpositivem, HER2-negativem Mammakarzinom im fortgeschrittenen Stadium als Entscheidungskriterium herangezogen werden kann, ob eine endokrine Therapie (ET) ausreichend oder eine Chemotherapie mit anschließender endokriner Therapie (CTX) notwendig ist[65]. Hierfür wurden 761 Patientinnen in die prospektiv randomisierte Phase-III-STIC-CTC-Studie eingeschlossen.…”