Drug combination not of benefit in inflammatory breast cancer

Share this article:

Administering pazopanib (Votrient) with lapatinib (Tykerb) to combat inflammatory breast cancer produces greater toxicity than using lapatinib alone with no significant clinical benefit, recent research indicates.

Inflammatory breast cancer becomes even more aggressive in persons with tumors expressing the ErbB2 receptor. Lapatinib, an ErbB2 inhibitor, can slow the progression of the disease when other chemotherapy has been unsuccessful. Pazopanib, approved for use in advanced renal cell carcinoma to target vascular endothelial growth factor receptor (VEGFR) and thus inhibit the growth of new blood vessels, was added to the lapatinib regimen to test the effectiveness of this combination therapy in inflammatory breast cancer.

In the multicenter phase II trial, 76 patients with relapsed inflammatory breast cancer, ErbB2-positive tumors, and prior treatment with trastuzumab (Herceptin) were randomized to receive the dual therapy or lapatinib plus placebo. The 38 participants who received both pazopanib and lapatinib had an overall response rate of 45% and median progression-free survival of 14.3 weeks, compared with a 29% overall response rate and median progression-free survival of 16.1 weeks for the 38 patients receiving lapatinib only.

The most frequent adverse events of grade 3 or higher were much more common in the combination-therapy arm, including diarrhea (18% vs 0% for lapatinib only), vomiting (8% vs 0%), increased alanine aminotransferase (ALT) levels (8% vs 0%), neutropenia (13% vs 3%), and increased bilirubin (5% vs 0%).

In a second cohort, overall response rates were 47% for 36 patients given lapatinib only, 31% for 14 patients given pazopanib only, and 58% for 38 patients receiving both drugs. Median progression-free survival for the three subsets were 16.0, 11.4, and 16.0 weeks, respectively.

Once again, the most frequent adverse events of grade 3 or higher were largely confined to the two-drug group: ALT levels were increased in 21% of the patients receiving lapatinib plus pazopanib but in none of the other patients; aspartate aminotransferase (AST) levels were increased in 18% of the lapatinib-plus-pazopanib users but in none of the others; diarrhea of grade 3 or higher struck 8% of the lapatinib-plus-pazopanib patients, 8% of the pazopanib-only patients, and 3% of the lapatinib-only patients; and fatigue of grade 3 or higher also struck 8% of the lapatinib-plus-pazopanib patients, 8% of the pazopanib-only patients, and 3% of the lapatinib-only patients.

Led by Massimo Cristofanilli, MD, of the Fox Chase Cancer Center in Philadelphia, Pennsylvania, the researchers reported that their work confirmed the clinical activity of lapatinib as a single-agent treatment in metastatic ErbB2-positive inflammatory breast cancer, and demonstrated increased toxicity associated with the combination therapy without a clinical meaningful improvement in efficacy. The findings were presented at the annual meeting of the American Society of Clinical Oncology, held June 1-5, 2012, in Chicago, Illinois (Abstract # 531).

Share this article:
You must be a registered member of ONA to post a comment.

Sign Up for Free e-newsletters

April Contest: Win a Pebble Watch

Start the contest today

Regimen and Drug Listings

GET FULL LISTINGS OF TREATMENT Regimens and Drug INFORMATION

Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Genitourinary Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Rare Cancers Regimens
Skin Cancer Regimens Drugs

More in Web Exclusives

Genes may predict the need for further cancer treatments

A new predictive tool is being developed that could help patients with breast cancer and certain lung cancers decide whether follow-up treatments are likely to help.

Early promise from therapy targeting FGFR mutations

The investigational drug BGJ398 showed promising anticancer activity in patients with various types of cancer driven by FGFR genetic alterations.

New immunotherapy promising for advanced melanoma

A new type of immunotherapy that directs patients' immune responses toward tumor cell killing, IMCgp100, showed efficacy in some patients with advanced melanoma.