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Purpose: To assess whether panitumumab is active in patients with cetuximab-refractory metastatic colorectal cancer (mCRC). Patients and Methods: Eligible patients had pretreated RAS (renin–angiotensin system) wild-type mCRC that progressed after cetuximab treatment, after having shown either objective response or stable disease. A minimax two-stage design was applied, with progression-free rate at 2 months as the primary end point. At least 12 of 28 and 21 of 41 successes at the first and second stage, respectively, were required for a positive result. Panitumumab 6 mg/kg was provided every 2 weeks, until progression or unacceptable toxicity. Results: Overall, 52 patients with KRAS (Kirsten rat sarcoma viral oncogene) wild-type disease were enrolled, but 11 were found to have mutated disease after all-RAS retesting. Among 41 eligible patients, median time since diagnosis was 38 months, and 71% experienced an objective response to previous cetuximab. First stage was passed with 12 of 28 patients alive without progression at 2 months. At the second stage, 17 of 41 patients were alive without progression at 2 months. At a median follow-up of 21.8 months, 35 patients experienced disease progression, and 26 died. Median progression-free survival was 2.1 months (95% confidence interval, 1.8-3.6) and median overall survival 6.8 months (95% confidence interval, 4.6-16.6). Most of the patients experienced no adverse reactions; 25% of patients had grade 3 rash. Conclusion: According to our study design, panitumumab was not effective in patients with cetuximab-refractory RAS wild-type mCRC. PACER is a phase 2 study aiming to assess whether panitumumab monotherapy is active in patients with cetuximab-refractory metastatic colorectal cancer. Primary end point was 2-month progression-free rate. According to a minimax two-stage design, 28 and 41 patients were required at the two stages, respectively. Panitumumab was shown to be not active at the second stage. The study failed to demonstrate the experimental hypothesis.

Targeted therapies are causing a dramatic change in cancer drug development. Trastuzumab, a humanised recombinant monoclonal antibody that recognizes the extracellular domain of HER2 trans-membrane protein, is among the first target-specific drugs that have been licensed for clinical use and its development represents a model of integration of new agents with classical treatment strategies. In preclinical models, trastuzumab has demonstrated a marked antiproliferative effect and a synergistic action with several chemotherapeutic agents. Monotherapy trials indicate that trastuzumab is active as a single agent in HER2 positive patients, is well tolerated, and is associated with preservation of quality of life (QoL). Furthermore, as first line therapy for metastatic breast cancer overexpressing HER2 receptor, the addition of trastuzumab to taxane-based chemotherapy significantly increased rate of objective response, time to disease progression and survival when compared with chemotherapy alone. Trastuzumab has shown important activity when used with many chemotherapeutic agents such as platinum salts, gemcitabine, vinorelbine and capecitabine and liposomal anthracyclines. Various trials are now ongoing to optimize the use of trastuzumab and to investigate its role in the adjuvant and in the neo-adjuvant setting.