Search

Erlotinib (Tarceva) is a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor initially approved by the US Food and Drug Administration for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer after failure of at least one prior chemotherapy regimen. In this report, we present the pivotal study that led to the approval of erlotinib in combination with gemcitabine (Gemzar) in patients with locally advanced/metastatic chemonaive pancreatic cancer patients. The combination demonstrated a statistically significant increase in overall survival accompanied by an increase in toxicity. Physicians and patients now have a new option for the treatment of locally advanced/metastatic adenocarcinoma of the pancreas.

Purpose: On May 17, 2007, doxorubicin HCl liposome injection (Doxil) in combination with bortezomib (Velcade) received approval from the US Food and Drug Administration (FDA) for the treatment of relapsed or refractory multiple myeloma after at least one prior therapy that has not included bortezomib. Liposomal doxorubicin's efficacy and safety were demonstrated in a phase III, randomized, multicenter, international trial comparing the combination of this agent plus bortezomib vs bortezomib alone in multiple myeloma patients who had not previously received bortezomib and had received at least one prior therapy. Here we summarize the FDA review of the data that support this approval., Experimental Design and Results: An interim analysis of time to disease progression (TTP), the primary endpoint, was conducted after 249 TTP events in this study that randomized 324 patients to liposomal doxorubicin plus bortezomib treatment and 322 patients to bortezomib monotherapy. Time to progression was significantly prolonged in the combination arm (median TTP = 9.3 months) compared with bortezomib monotherapy (median TTP = 6.5 months), P < .0001 (log-rank test); hazard ratio = 0.55 (95% confidence interval = 0.43-0.71). The response rates were similar between the two arms and not statistically different; however, among responding patients, the median duration of response was longer with the combination--10.2 months compared to 7.0 months in the monotherapy arm. Adverse reactions occurred more frequently with the combination therapy. As compared to the monotherapy, frequent grade 3/4 adverse reactions with the combination were neutropenia and thrombocytopenia., Conclusions: Liposomal doxorubicin received FDA approval for use in combination with bortezomib in patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy.

Purpose: Topotecan, a camptothecin analog previously approved for the treatment of ovarian cancer and small-cell lung cancer, was granted regular approval by the US Food and Drug Administration (FDA) on June 14, 2006, for use in combination with cisplatin to treat women with stage IVB, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment with surgery and/or radiation therapy. The purpose of this summary is to review the database supporting this approval., Experimental Design: In a randomized multicenter study enrolling 293 eligible patients, topotecan plus cisplatin (TC) was compared with cisplatin monotherapy. The TC regimen consisted of cisplatin 50 mg/m2 IV over 1 hour on day 1 and topotecan 0.75 mg/m2 IV over 30 minutes on days 1, 2, and 3 every 21 days., Results: There was a clinically relevant and statistically significant improvement in overall survival in the TC treatment arm. Median overall survival was 9.4 months (95% confidence interval [CI]:7.9-11.9) in the TC arm, compared to 6.5 months (95% CI:5.8-8.8) with cisplatin alone. The unadjusted hazard ratio for overall survival between treatment arms was 0.76 (95% CI: 0.59-0.98, P = .033) favoring the combination arm. The most common toxicities with TC included myelosuppression, nausea and vomiting, mucositis, rash, and hepatotoxicity., Conclusions: This report describes the FDA's review supporting this first approval of a chemotherapeutic drug for advanced cervical cancer based on demonstration of a survival benefit.