SABCS--four drug combination effective (50% cpr) in small neoadjuvant study

[Lani]

SABCS: 4-Drug Combo Effective in Breast CA


SAN ANTONIO -- Preliminary results of a neoadjuvant breast cancer therapy trial for HER2-positive tumors shows that a four-drug combination has a high pathological complete response rate, researchers said here.
The treatment -- a run-in cycle of trastuzumab (Herceptin) and lapatinib (Tykerb), followed by a chemotherapy regimen with docetaxel (Taxotere), carboplatin (Paraplatin), trastuzumab, and lapatinib for six more cycles -- allowed 9 of 18 evaluable patients to achieve a pathologic complete response.

"This is the first report of this four-drug combination in early breast cancer among women with HER2-positive status," said Rena Callahan, MD, a fellow in hematology/oncology at the University of California Los Angeles.

Callahan reported here at the San Antonio Breast Cancer Symposium on results from the 20-patient, four-drug arm -- known as Arm C -- of the initial Phase II study. Still to be recruited are 120 more patients for Arm A -- trastuzumab and lapatinib followed by docetaxel and carboplatin with just trastuzumab; and Arm B -- trastuzumab and lapatinib followed by docetaxel and carboplatin with just lapatinib.

The median age of the 20 patients in the study was 50 years; 19 of the women had invasive ductal cancer and one woman had invasive lobular cancer. Nine of the women were estrogen receptor- and progesterone receptor-positive; 3 were estrogen receptor-positive and progesterone receptor-negative; and the remaining 8 women were estrogen and progesterone receptor-negative.

In the run-in phase, patients were administered 1000 mg of lapatinib on days 1 through 21, plus trastuzumab at a dose of 8 mg/kg intravenously. Then they received docetaxel 75 mg/m2 and carboplatin to an Area Under the Curve (AUC) 5 or 6, as well as trastuzumab 6 mg/kg and lapatinib 1000 mg daily for six 21-day cycles.

Of the 12 estrogen receptor-positive women, four achieved a pathological complete response, while five of the eight of the women with estrogen receptor-negative tumors achieved a pathological complete response.

Callahan said that the most common serious adverse effect encountered in the study was diarrhea, with six patients experiencing Grade 3 diarrhea. All of the patients in the study complained of some diarrhea, but only one person discontinued treatment due to diarrhea. Two other patients discontinued due to infection with Clostridium difficile and anemia.

The patient with C. difficile underwent the run-in phase of the trial and three cycles of four-drug treatment before stopping therapy. She underwent surgery and was found to have achieved a pathologic complete response.

In terms of other serious adverse events, four patients experienced grade 3 or 4 neutropenia. In addition, four patients experienced serious infections and three patients developed Grade 3 or 4 hypokalemia. No other Grade 3 events occurred in more than two individuals.

There were no deaths in the treatment program, which lasted for five months.

"We found that the combination of docetaxel, carboplatin, trastuzumab plus lapatinib had manageable toxicity," Callahan said at her poster presentation, which was surrounded by interested clinicians.

"We are finding that some of these combinations in neoadjuvant therapies for early breast cancer may be synergistic," said Jennifer K. Litton, assistant professor of medicine at the University of Texas MD Anderson Cancer Center in Houston.

"These types of preliminary trials are setting up what may prove to be the next practice-changing studies," Litton told MedPage Today.

Edith Perez, MD, deputy director of the Mayo Clinic comprehensive Cancer Center, Jacksonville, Fla., told MedPage Today that the studies trying to find the ideal neoadjuvant therapy are "an attempt to find the right combination for the right patients" to hit the cancer hard early, so that treatment for recurrence would not be required.




Primary source: San Antonio Breast Cancer Symposium