Maurizio Scaltriti's preclinical work corroborated in humans CHER-LOB trial results

[Lani]

additing herceptin and lapatinib creates supersynergism:
J Clin Oncol. 2012 Apr 9. [Epub ahead of print]
Preoperative Chemotherapy Plus Trastuzumab, Lapatinib, or Both in Human Epidermal Growth Factor Receptor 2-Positive Operable Breast Cancer: Results of the Randomized Phase II CHER-LOB Study.
Guarneri V, Frassoldati A, Bottini A, Cagossi K, Bisagni G, Sarti S, Ravaioli A, Cavanna L, Giardina G, Musolino A, Untch M, Orlando L, Artioli F, Boni C, Generali DG, Serra P, Bagnalasta M, Marini L, Piacentini F, D'Amico R, Conte P.
Source
Valentina Guarneri, Antonio Frassoldati, Federico Piacentini, Roberto D'Amico, and PierFranco, Modena University Hospital, Modena; Alberto Bottini and Daniele Giulio Generali, AO Istituti Ospitalieri di Cremona, Cremona; Katia Cagossi and Fabrizio Artioli, Ramazzini Hospital, Carpi; Giancarlo Bisagni and Corrado Boni, Arcispedale Santa Maria Nuova, Reggio Emilia; Samanta Sarti and Patrizia Serra, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola; Alberto Ravaioli, Ospedale Infermi, Rimini; Luigi Cavanna, Hospital of Piacenza, Piacenza; Giovanni Giardina, Ospedale di Circolo e Fondazione Macchi, Varese; Antonino Musolino, University Hospital of Parma, Parma; Laura Orlando, Antonio Perrino Hospital, Brindisi; Michela Bagnalasta and Luca Marini, GlaxoSmithKline, Verona, Italy; and Michael Untch, Helios Klinikum Berlin-Buch, Berlin, Germany.
Abstract
PURPOSEThis is a noncomparative, randomized, phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab plus lapatinib in patients with human epidermal growth factor receptor 2 (HER2) -positive, stage II to IIIA operable breast cancer. The primary aim was to estimate the percentage of pathologic complete response (pCR; no invasive tumor in breast and axillary nodes). PATIENTS AND METHODSIn the three arms, chemotherapy consisted of weekly paclitaxel (80 mg/m(2)) for 12 weeks followed by fluorouracil, epirubicin, and cyclophosphamide for four courses every 3 weeks. The patients randomly assigned to arm A received a 4-mg loading dose of trastuzumab followed by 2 mg weekly; in arm B patients received lapatinib 1,500 mg orally (PO) daily; and in arm C, patients received trastuzumab and lapatinib 1,000 mg PO daily.ResultsA total of 121 patients were randomly assigned. Diarrhea and dermatologic and hepatic toxicities were observed more frequently in patients receiving lapatinib. No episodes of congestive heart failure were observed. The rates of breast-conserving surgery were 66.7%, 57.9%, and 68.9% in arms A, B and C, respectively. The pCR rates were 25% (90% CI, 13.1% to 36.9%) in arm A, 26.3% (90% CI, 14.5% to 38.1%) in arm B, and 46.7% (90% CI, 34.4% to 58.9%) in arm C (exploratory P = .019). CONCLUSIONThe primary end point of the study was met, with a relative increase of 80% in the pCR rate achieved with chemotherapy plus trastuzumab and lapatinib compared with chemotherapy plus either trastuzumab or lapatinib. These data add further evidence supporting the superiority of a dual-HER2 inhibition for the treatment of HER2-positive breast cancer.
PMID: 22493419