Un anticorpo monoclonale nel carcinoma polmonare

A Phase II study of Pfizer's investigational anti-insulin growth factor type 1 receptor (IGF-1R) antibody, figitumumab (CP-751,871), met its primary endpoint of objective response rate (ORR) in patients with non-small cell lung cancer (NSCLC). Exploratory analyses of ORR and progression-free survival (PFS), a secondary endpoint, by dose and histology suggest a dose-response relationship in patients with differentiated histologies (squamous cell carcinoma and adenocarcinoma) but not in patients with undifferentiated, not otherwise specified (NOS) tumors. Figitumumab was generally well-tolerated in the study. These data were published online ahead of print on April 20 in the Journal of Clinical Oncology.

Lung cancer is the most common cancer worldwide. NSCLC accounts for about 87 percent of lung cancer casesii and remains difficult to treat, particularly in the metastatic setting. Nearly 60 percent of NSCLC patients are diagnosed late with Stage IIIB/IV advanced disease.iii In these patients, the five-year survival rate is only two percent.iv

"This is the first formal report of Phase II data for an IGF-1R inhibitor in the treatment of lung cancer patients," said lead investigator Daniel Karp, M.D., director of The University of Texas

M.D. Anderson Cancer Center Clinical and Translational Research Center (CTRC). "Despite improvements in treatment, NSCLC remains a difficult-to-treat disease. We are encouraged by these data, which provide further rationale for exploring IGF-1R as one of the key signaling pathways implicated in uncontrolled growth and survival of cancer cells."

In this randomized, non-comparative study, 54 percent of the Stage III/IV treatment-naïve NSCLC patients (53 of the 98) who received the combination of figitumumab plus carboplatin and paclitaxel experienced an ORR (defined as complete responses + partial responses). Of the 53 patients taking carboplatin and paclitaxel alone, 42 percent (22 patients) experienced an ORR.

Of interest, patients with tumors of squamous cell histology appeared to benefit the most from the combined treatment. Seven of the nine patients receiving the combination of figitumumab 20 mg/kg and chemotherapy had objective responses, despite presenting with bulky (>5cm) squamous tumors when entering the study.i Furthermore, squamous cell tumors regressed further in two patients receiving figitumumab alone as maintenance, post chemotherapy.i The study has been extended to further characterize the activity of figitumumab in patients with these tumors. These data will be presented at the 2009 American Society Of Clinical Oncology (ASCO) Annual Meeting in Orlando from May 29 - June 2.

Although the study was not powered to compare across treatments, exploratory analyses of PFS (defined as either the length of time before the cancer progressed or death) were also conducted. PFS was longer for patients with tumors of differentiated histologies who received the combination of figitumumab 20 mg/kg and chemotherapy (HR=0.46 [95% CI, 0.18 to 0.75, p=0.0058, n=68]), but not in patients with NOS tumors.

"Pfizer is committed to improving the poor prognosis for patients with NSCLC and will continue to investigate figitumumab as a treatment option for them," said Antonio Gualberto, M.D., Ph.D, Pfizer Global Clinical Leader for figitumumab and corresponding author.

About the Study

In this Phase II, multi-center, open-label, non-comparative trial, 156 patients were randomized, 151 of whom were evaluable for safety and efficacy. Ninety-eight patients were randomized to figitumumab plus paclitaxel and carboplatin (10-20 mg/kg) and 53 patients were randomized to paclitaxel and carboplatin alone.

Forty-eight and 50 figitumumab plus carboplatin and paclitaxel patients received 10 and 20 mg/kg of figitumumab, respectively, in two sequential stages. The median number of chemotherapy cycles was four in both treatment arms. Twenty of 53 patients received figitumumab upon progression on chemotherapy alone.

An additional 30 patients with non-adenocarcinoma were enrolled in a single-arm cohort extension. Because the study was open-label and non- comparative, all safety and efficacy analyses across treatment arms were exploratory.

Figitumumab was generally well-tolerated in the study. In the figitumumab plus carboplatin and paclitaxel arm, the most frequent grade three or four side effects reported were hyperglycemia (15 percent), fatigue (10 percent) and neutropenia (26 percent). Three patients discontinued the study due to hyperglycemia, but it was generally manageable with insulin or oral anti-diabetic agents. No hypersensitivity reactions were seen in patients receiving figitumumab. There were eight deaths while on study treatments, three in patients receiving carboplatin and paclitaxel alone, three in those receiving 10 mg/kg of figitumumab plus carboplatin and paclitaxel, and two in those receiving 20mg/kg of figitumumab plus carboplatin and paclitaxel.i

Preliminary results of this Phase II study were most recently presented at the 33rd European Society of Medical Oncology (ESMO) Congress in Sweden in September, 2008.

About ADVIGO Phase III Registration Program (ADVancing IGF-1R in Oncology)

Pfizer recently initiated a large global Phase III clinical trial program for figitumumab in NSCLC, including studies in patients with non-adenocarcinoma (ADVIGO 1016, ADVIGO 1018). The program currently includes a trial for patients who are newly diagnosed and one for those who have already been treated with other therapies.

Pfizer is committed to the development of figitumumab and has invested significant resources in the Phase III program, which will include more than 1,500 patients around the world.

For more information on the ADVIGO registration program please visit, www.pfizeroncology.com/ADVIGOtrials

About Figitumumab (CP-751,871)

Figitumumab (CP-751,871), a fully human monoclonal antibody, is a highly specific inhibitor of the IGF-1R pathway. The IGF-1R pathway is generally thought to be one of the key signaling pathways in cancer cells that leads to uncontrolled growth and survival of tumor cells.

In addition to NSCLC, Pfizer is studying figitumumab in clinical trials for the potential treatment of many other cancers, including prostate, breast and colon cancers and Ewing's sarcoma. To date, more than 1,000 patients have participated in figitumumab clinical trials in multiple tumor types.

About Pfizer Oncology

Pfizer Oncology is committed to the discovery, investigation and development of treatments and currently has 22 innovative compounds in clinical development across four platforms. By leveraging the strength of our resources and scientific talent, Pfizer Oncology strives to discover and develop novel treatment options to improve the outlook for oncology patients. Pfizer currently devotes more than 22 percent of its total R&D budget to the field of oncology, investing annually in worldwide research initiatives. We also partner with healthcare providers, governments and local communities around the world to provide better quality healthcare and health system support.

For more information please visit www.Pfizer.com