Trastuzumab/Lapatinib Active in Refractory, KRAS Codon 12/13 Wild-Type, HER2-Positive Metastatic Colorectal Cancer


Key Points

  • Trastuzumab/lapatinib was active in patients with treatment-refractory HER2-positive metastatic colorectal cancer.
  • The combination was reported to be well tolerated.

Dual HER2 inhibition with trastuzumab (Herceptin) and lapatinib (Tykerb) was active in patients with refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer, according to an Italian phase II trial reported by Sartore-Bianchi et al in The Lancet Oncology.

Study Details

In the open-label study, screening of 914 patients with KRAS codon 12/13 wild-type disease at four Italian sites between August 2012 and May 2015 identified 48 (5%) with HER2-positive tumors. Of them, a total of 27 were refractory to standard treatment (including cetuximab [Erbitux] or panitumumab [Vectibix]) and were eligible for the trial and evaluable for response.

Patients received intravenous (IV) trastuzumab at a 4-mg/kg loading dose followed by 2 mg/kg once a week and oral lapatinib at 1,000 mg a day until disease progression. The primary endpoint was the proportion of patients achieving an objective response on independent central review.

Responses and Toxicity

At a median follow-up of 94 weeks, response had occurred in eight patients (30%, 95% confidence interval [CI] = 14%–50%), with complete response in one (4%). An additional 12 patients (44%, 95% CI = 25%–63%) had stable disease. Median time to response was 8 weeks. Median duration of response was 38 weeks.

Overall, six patients (22%) had grade 3 adverse events, consisting of fatigue in four, rash in one, and increased bilirubin in one; no grade 4 or 5 adverse events were observed. No drug-related serious adverse events were reported. No patients had treatment interrupted or withdrew from treatment due to adverse events.

The investigators concluded: “The combination of trastuzumab and lapatinib is active and well tolerated in treatment-refractory patients with HER2-positive metastatic colorectal cancer.”

The study was funded by Associazione Italiana Ricerca Cancro, Fondazione Oncologia Niguarda Onlus, and Roche.

Silvia Marsoni, MD, of the Istituto di Candiolo, Fondazione del Piemonte per l’Oncologia-IRCCS, is the corresponding author of The Lancet Oncology article.

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