Phase Ib dose-finding trial of lapatinib plus pegylated liposomal doxorubicin in advanced HER2-positive breast cancer

• Published in: Cancer chemotherapy and pharmacology 2017-05, Vol.79 (5), p.863-871
• Main Authors: Rocca, Andrea, Cecconetto, Lorenzo, Passardi, Alessandro, Melegari, Elisabetta, Andreis, Daniele, Monti, Manuela, Maltoni, Roberta, Sarti, Samanta, Pietri, Elisabetta, Schirone, Alessio, Fabbri, Francesco, Donati, Caterina, Nanni, Oriana, Fedeli, Anna, Faedi, Marina, Amadori, Dino
• Format: Article
• Language: English
• Subjects: Aged; anorexia; Antibiotics, Antineoplastic - administration & dosage; Antineoplastic Agents - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - blood; breast neoplasms; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Cancer Research; cardiotoxicity; colitis; diarrhea; doxorubicin; Doxorubicin - administration & dosage; Female; Humans; intravenous injection; Liposomes; Maximum Tolerated Dose; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original; Original Article; Pharmacology/Toxicology; Polyethylene Glycols; Protein Kinase Inhibitors - administration & dosage; Quinazolines - administration & dosage; Receptor, ErbB-2 - genetics; Survival Analysis; transaminases; Treatment Outcome
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-017-3279-8

Purpose Combination of anthracyclines with trastuzumab is hampered by cardiotoxicity. Pegylated liposomal doxorubicin and lapatinib could represent a safer alternative to combination therapy. Methods In this phase Ib study with 3 + 3 dose escalation design, patients with HER2-positive advanced breast cancer received pegylated liposomal doxorubicin 30 mg/m 2 intravenously on day 1 plus lapatinib 1250 (level 1) or 1500 (level 2) mg/day orally on days 1–21 of each 21-day cycle. The aims were to establish the maximum tolerated dose at first cycle, and the activity and safety of multiple cycles. Results Nine patients out of 11 enrolled were evaluable: 3 at level 1 and 6 at level 2. No dose-limiting toxicities occurred at dose level 1, while 1 (grade 3 diarrhea) occurred at dose level 2, leading to the expansion of this cohort to 6 patients, with no further dose-limiting toxicities. Main grade 1–2 toxicities at first cycle were leucopenia, diarrhea, elevated transaminases, mucositis. Three patients had grade 3 toxicities at subsequent cycles, including colitis, anorexia, stomatitis plus hand-foot syndrome. One partial response, 5 disease stabilizations, and 3 disease progressions were reported. Conclusions Combination of pegylated liposomal doxorubicin and lapatinib is feasible and potentially active in pretreated HER2-positive advanced breast cancer patients. Trial registration NCT02131506 (ClinicalTrials.gov identifier).