A phase II, open-label, multicenter study of GW572016 in patients with trastuzumab-refractory metastatic breast cancer

e11087 Background: Lapatinib-capecitabine is approved for the treatment of ErbB2-amplified metastatic breast cancer (MBC) after failure to anthracyclines, taxanes and trastuzumab. GLICO-0801 evaluates different lapatinib-based chemotherapy combinations as 1st/2nd line treatment for ErbB2 amplified MBC progressing after taxane treatment. We present the results of a planned safety interim analysis. Methods: This is an open-label, randomized, international, phase II trial exploring lapatinib (L) 1250mg qd in combination with capecitabine 2000mg/m2 d 1-14 (Arm A) or vinorelbine 25mg/m2 d 1 and 8 (Arm B) or gemcitabine 1000mg/m2 d 1 and 8 (Arm C). Primary objective is to determine the clinical benefit rate (defined as CR+PR+SD for ≥24 weeks). This trial is registered at www.clinicaltrials.gov number: NCT01050322 Results: The first83 randomized patients (pts) (Arm A=29, B=28 and C=26) were included in this analysis. Of them, 65 (78%) have discontinued therapy with mean number of cycles of 4.7, 6.2 and 7.5 in arms A, B and C respectively. Eighteen (21%) pts are still on treatment. Median age was 52y (29-84); 80 pts (96%) had PS 0-1; 51 (61%) were postmenopausal. Fifty-six pts (67%) had visceral metastasis, 52 (63%) were treated as 2nd line therapy and 36 (43%) had received prior trastuzumab. Most reported adverse events (AE) (87%) were grade 1-2. The most common AE (any grade) in arm A: diarrhea 72%, hand-foot syndrome 45%, vomiting 39%, anemia 36%; in arm B: diarrhea 75%, neutropenia 68%, nausea 43%, vomiting 39%; in arm C: diarrhea 72%, neutropenia 60%, anemia 44%, increase in ALT 44%. The most frequent serious AE reported in arm A: diarrhea in 3 pts (10%) and thrombocytopenia in 2 pts (7%); in arm B: febrile neutropenia in 2 pts (7%) and in arm C: sepsis in 1 pt (4%). There was one toxic death related to chemotherapy in arm C. Conclusions: There were no unexpected toxicities so far in this trial with most AEs being mild to moderate and manageable. This interim analysis supports the continuation of the study.

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Pharmacokinetics, safety, and early activity of a nanoparticle micellar formulation of docetaxel in women with metastatic breast cancer: Results of two randomized trials (phase I and II).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.3526 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 3526-3526 ◽

Cited By ~ 1

Author(s):

Markus Joerger ◽

Helena Bjermo ◽

Per Blom ◽

Nina Anna Heldring

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Phase Ii ◽

Intravenous Infusion ◽

Phase Ii Study ◽

Metastatic Breast ◽

Third Party ◽

Controlled Study ◽

Open Label ◽

Early Activity

3526 Background: Docetaxel micellar (DM) is a nano-sized particle formulation of docetaxel in which a retinoic acid derivative is used as solubilizer with a high drug to excipient ratio possibly resulting in reduced systemic toxicity or hypersensitivity reactions due to the excipient. DM is given without standard use of premedication, avoiding steroid-associated immunosuppression. Here we present the pharmacokinetics (PK) after a single dose of DM or polysorbate-solubilized docetaxel (D) as well as safety and early activity including overall response rate (ORR) in female patients with metastatic breast cancer. Methods: The PK study was a two-cycle, cross-over study where 30 patients were included and randomized to either DM followed by D or D followed by DM, both given as a 1-hour intravenous infusion at a dose of 100mg/m2. The phase II study was a prospective, multicenter, open-label, third-party blinded, randomized, parallel group, active-controlled study including 200 patients to compare the early activity and safety of DM and D, both given as 100 mg/m2 1-hour intravenous infusion every 21 days (1 cycle) for a total of 6 cycles. Results: Bioequivalence of total docetaxel in plasma, AUC0-last and Cmax, was demonstrated for DM compared to D. The incidence of adverse events was higher in the D arm than in the DM arm for the majority of SOCs and PTs in the phase II study. Overall, Grade 3 or 4 AEs were reported for 82.7% of patients from DM arm and 99.0% of patients from D arm. Twelve (12.2%) patients in the DM arm and 24 (24.0%) patients in the D arm needed at least one dose reduction due to AEs. The primary efficacy endpoint in the phase II study was based on the assessment according to Response Evaluation Criteria in Soldid Tumors (RECIST) 1.1 and non-inferiority was not reached based on the pre-defined non-inferiority margin. A post-hoc analysis investigating the ORR based on tumour assessment at the end of chemotherapy, and non-inferiority of DM as compared to D was shown (ITT population). Conclusions: DM is bioequivalent to D regarding total drug in plasma and provides a docetaxel formulation that spares patients steroid premedication. An improved safety profile for DM compared to D was shown while additional efficacy data is needed for future development of DM. Eudra CT: 2012-005161-12 and 2013-004889-33. Clinical trial information: 2012-005161-12 and 2013-004889-33 .

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