Panitumumab Monotherapy Research Articles

1266 POSTER Euthanasia: evaluation of a protocol

This phase 2 estimation study evaluated docetaxel/cisplatin with/without panitumumab, an anti–epidermal growth factor receptor monoclonal antibody, as first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN).Randomized patients received docetaxel/cisplatin (75 mg/m2 each) with/without panitumumab (9 mg/kg) in 21-day cycles. Patients randomized to panitumumab + chemotherapy could continue panitumumab monotherapy after completing six chemotherapy cycles without progression; patients randomized to chemotherapy alone could receive second-line panitumumab after progression. Progression-free survival (PFS) was the primary endpoint. Secondary endpoints included overall survival (OS), overall response rate (ORR), time to response (TTR), duration of response (DOR), and safety. A protocol amendment limited enrollment to patients <70 years owing to excess toxicity in older patients and added mandatory pegfilgrastim/filgrastim support. Outcomes were also analyzed by human papillomavirus status.103 of the 113 enrolled patients were evaluable and randomized to receive ⩾1 dose of first-line treatment. Median PFS for panitumumab + chemotherapy was 6.9 (95% CI = 4.7–8.3) months versus 5.5 (95% CI = 4.1–6.8) months for chemotherapy alone (hazard ratio [HR] = 0.629; 95% CI = 0.395–1.002; P = 0.048). ORR for panitumumab + chemotherapy was 44% (95% CI = 31–58%) versus 37% (95% CI = 24–51%) for chemotherapy alone (odds ratio [OR] = 1.37; 95% CI = 0.57–3.33). Median OS for panitumumab + chemotherapy was 12.9 (95% CI = 9.4–18.5) months versus 13.8 (95% CI = 11.8–22.9) months for chemotherapy alone (HR = 1.103; 95% CI = 0.709–1.717). Median TTR for panitumumab + chemotherapy treatment was 6.9 weeks versus 11.0 weeks for chemotherapy alone. Median DOR was 8.0 (95% CI = 5.7–11.1) months with panitumumab + chemotherapy versus 5.1 (95% CI = 4.4–7.2) months with chemotherapy alone. Grade 3/4 adverse event incidence was 73% with panitumumab + chemotherapy versus 56% with chemotherapy alone. 41% and 55% of patients in the panitumumab + chemotherapy and chemotherapy-alone arms, respectively, received panitumumab monotherapy.The addition of panitumumab to docetaxel/cisplatin may improve PFS in recurrent/metastatic SCCHN and has the potential to improve outcomes in these fully, or mostly, active patients.

Updated results from a dose and schedule study of Panitumumab (ABX-EGF) monotherapy, in patients with advanced solid malignancies

3059 Background: Panitumumab is a fully human monoclonal antibody to the epidermal growth factor receptor (EGFr). This open-label, multiple-infusion, dose-escalation trial evaluated the safety, pharmacokinetics (PK), and antitumor activity of panitumumab in advanced solid tumor patients. Methods: Sequential cohorts of patients were enrolled to receive four infusions at different dose levels and schedules of panitumumab monotherapy ranging from 0.01 to 5.0 mg/kg once per week (QW), 6.0 mg/kg once every 2 weeks (Q2W) or 9.0 mg/kg once every 3 weeks (Q3W) administered IV over one hour without premedication. Patients were prescreened for EGFr expression and had to have at least 1+ expression in ≥10% of tumor cells. Stable or responding patients were eligible for extended panitumumab treatment on a separate protocol for six additional months or until disease progression. Patients had to have acceptable organ function, and may have received prior systemic anti-tumor therapy. Preliminary results are presented below. Results: Ninety-six patients (72 [75%] men) were treated with panitumumab. The mean age was 60.4 yrs (range 32–79). Tumor types included 39 colorectal (CRC), 14 lung, 3 pancreatic, 21 prostate, 15 renal, 3 esophageal/gastrosophageal, and 1 anal cancer. The incidence of skin-related toxicities was dose dependent and plateaued at >2.0 mg/kg QW. Grade 3 or 4 related adverse events were noted in 10% of patients with grade 3 skin-related toxicities being the most frequent (7% of patients). No MTD was reached. No human anti-human antibody formation or infusion related reactions were observed. PK exposure was similar between 2.5 mg/kg QW, 6 mg/kg Q2W and 9 mg/kg Q3W. By investigator assessment, 5 confirmed partial responses (WHO) (12.8% RR, 5/39 CRC patients), 1 minor PSA response, and 18 patients with stable disease were observed. Conclusions: Panitumumab is generally well tolerated. The exposure and tolerability profile is comparable between QW, Q2W, and Q3W schedules. Panitumumab has single agent anti-tumor activity in solid tumors, most notably in subjects with advanced CRC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abgenix, Amgen

Safety and efficacy of panitumumab monotherapy in patients with metastatic colorectal cancer (mCRC)

3520 Background: Panitumumab (formerly ABX-EGF) is a fully human monoclonal antibody that binds with high affinity to the epidermal growth factor receptor (EGFr). This ongoing phase 2 study is evaluating the safety and efficacy of panitumumab monotherapy in patients (pts) with mCRC who have failed standard chemotherapy. Here we present mature unaudited data from the ongoing study. Methods: Pts with mCRC who failed therapy with a fluoropyrimidine (± leucovorin) and either irinotecan or oxaliplatin, or both, were eligible for this study. Cohort A included pts with EGFr staining of 2+ or 3+ in ≥ 10% tumor cells; cohort B included pts with EGFr staining of the sum of 1+, 2+ and 3+ in ≥ 10% of tumor cells, but with the sum of 2+ and 3+ in < 10% of tumor cells. Panitumumab was given IV at 2.5 mg/kg once weekly in 8-wk cycles. Pts continued receiving treatment until disease progression or unacceptable toxicity occurred. Endpoints included tumor response (RECIST), time to disease progression, survival, and safety. Results: Enrollment is complete, with treatment ongoing. In total, 148 pts were treated (82 men/66 women; ECOG status of 1 [n = 111] or 0 [n = 37]; mean age 59 yrs [range 21 - 88 yrs]). Efficacy results are shown in the table. The 4 most frequently reported grade (gr) 3 or 4 treatment-related adverse events (AEs) were rash NOS (5 pts), fatigue (4 pts), vomiting NOS (2 pts), nausea (1 pt), and pruritus (1 pt). Skin toxicity-related AEs were reported for 141 pts (95%; 5% gr 3 and no gr 4). One infusion-related gr 3 AE, which did not require dose modification, was reported; no other infusion-related AE has been reported to date. No human anti-human antibodies were observed in 145 pts tested. Conclusions: These mature data confirm previously reported safety and response findings (Hecht et al, 2004) and provide encouraging survival data in pts with mCRC who have failed multiple lines of standard chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen, Genentech, Pfizer, Sanofi Amgen Amgen, Bristol-Myers Squibb, Genentech, Novartis, Pfizer, Roche Amgen, Eli Lilly, Pfizer, Roche Amgen

302 Patterns of gene expression can prospectively predict Panitumumab (ABX-EGF) monotherapy responsiveness in xenograft models

302 Patterns of gene expression can prospectively predict Panitumumab (ABX-EGF) monotherapy responsiveness in xenograft models