Older Chemotherapy Studies in Breast Cancer Coming of Age

Get Permission

Maintenance PG chemotherapy after six cycles should be considered in metastatic breast cancer patients with hormone receptor–negative tumors, visceral disease, high tumor burden, young age (< 50 years), and premenopausal status.

—Young-Hyuck Im, MD

Results of several long-running chemotherapy trials were reported at the 2012 ASCO Annual Meeting breast cancer oral session, reported in brief here.


The final analysis of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-38 trial showed that the addition of gemcitabine (G) to a dose-dense regimen of doxorubicin/cyclophosphamide (AC) followed by paclitaxel (P) did not improve outcomes over AC→P alone or compared to the standard docetaxel/doxorubicin/cyclophosphamide (TAC) regimen in patients with breast cancer.1

“Gemcitabine did not improve outcome and the other regimens had differing toxicities, which can be taken into consideration when considering which treatment to offer a patient,” said Sandra M. Swain, MD, of the Washington Cancer Institute at the MedStar Washington Hospital Center in Washington, DC.

The study enrolled 4,894 women with operable, node-positive breast cancer, randomly assigning them to (1) AC × 4 followed by paclitaxel × 4 every 2 weeks, (2) the same regimen plus gemcitabine given with the paclitaxel, or (3) TAC every 3 weeks × 6. Disease-free survival at 5 years was 82.2% with dose-dense AC→P, 80.6% with dose-dense AC→PG, and 80.1% with standard TAC. Overall survival was approximately 90% in all arms.

The toxicity profiles, however, differed, with more neuropathy and anemia observed on the dose-dense arms and more diarrhea and febrile neutropenia on TAC. An exploratory analysis showed no outcome differences according to whether or not patients received erythropoietin.


The role of weekly paclitaxel in node-negative patients with breast cancer is being evaluated in the phase III Spanish Breast Cancer Research Group (GEICAM)/2003-02 trial, and the first efficacy analysis was reported at ASCO.2 The study randomly assigned 1,925 postsurgical patients with high-risk node-negative disease to adjuvant chemotherapy with fluorouracil/doxorubicin/cyclophosphamide (FAC) × 6 or FAC × 4 followed by weekly paclitaxel at 100 mg/m2 for eight cycles.

“Adjuvant FAC plus paclitaxel was associated with a slight but significant improvement in [disease-free survival] with respect to FAC,” said Miguel Martin, MD, of the Hospital General Universitario Gregorio Marañon in Madrid. Disease-free survival rates were 93% vs 90%, respectively, at 5 years, representing a 27% reduction in risk (P = .0441). Overall survival was similar; the 24% reduction in deaths on the weekly paclitaxel arm was not statistically significant (P = .26).

Both regimens were well tolerated. The addition of paclitaxel slightly increased grade 3/4 sensory neuropathy, fatigue, infection, irregular menses, and thrombosis, but the greater number of cycles in the FAC arm apparently contributed to more late cardiac toxicity.

Dr. Martin acknowledged that the study was initiated 10 years ago, and with genomic testing, many of these patients would not have received chemotherapy at all. “We are going to evaluate these findings using Oncotype DX in tissue samples,” he said.

KCSG-BR 0702/NCT00561119

In patients with metastatic breast cancer who achieve disease control (complete response plus partial response plus stable disease) with paclitaxel/gemcitabine (PG), maintenance with the same regimen doubled the time to progression and improved overall survival, vs observation, in this phase III Korean study of 324 patients. Patients received six cycles of PG, and the responders (complete or partial response or stable disease) were randomized to observation or to continued treatment with the regimen.

“Maintenance PG chemotherapy after six cycles should be considered in metastatic breast cancer patients with hormone receptor–negative tumors, visceral disease, high tumor burden, young age (< 50 years), and premenopausal status,” said Young-Hyuck Im, MD, of Samsung Medical Center in Seoul, South Korea.

From the time of randomization, progression-free survival was 3.8 months in the observation arm and 7.5 months in the maintenance arm, for a 27% reduction in risk (P = .026); 6-month progression-free survival was 60% vs 36% (P = .00023), respectively. Toxicities were manageable, and no impairment in quality of life was observed with maintenance. ■

Disclosure: Dr. Swain has served in an uncompensated consulting or advisory role for Genentech, Nektar Therapeutics, Novartis, Roche, and Sanofi, has received research funding from Bristol-Myers Squibb, Novartis, Pfizer, Roche/Genentech, and Sanofi, and has received other remuneration from Sanofi. Dr. Martin has served in a consulting or advisory role for Amgen, Genomic Health, and Roche. Dr. Im reported no potential conflicts of interest.


1. Swain SM, Tang G, Geyer CE, et al: NSABP B-38: definitive analysis of a randomized adjuvant trial comparing dose-dense AC→ paclitaxel plus gemcitabine with DD AC→P and with docetaxel, doxorubicin, and cyclophosphamide (TAC) in women with operable, node-positive breast cancer. ASCO 2012. Abstract LBA1000. Presented June 5, 2012.

2. Martin M, Lluch A, Ruiz A, et al: Randomized phase III study of adjuvant chemotherapy for high-risk node-negative breast cancer comparing FAC with FAC followed by weekly paclitaxel: First efficacy analysis of the GEICAM/2003-02 trial. 2012 ASCO Annual Meeting. Abstract 1001. Presented June 5, 2012.

3. Im YH, Park YH, Jung KH, et al: A phase III, multicenter, randomized trial of maintenance versus observation after achieving clinical responses in patients with metastatic breast cancer who received six cycles of gemcitabine plus paclitaxel as first-line chemotherapy. 2012 ASCO Annual Meeting. Abstract 1003. Presented June 5, 2012.