NEW ORLEANS-An international phase III study has found the combination of gemcitabine (Gemzar) plus paclitaxel to be superior to single-agent paclitaxel in the front-line treatment of metastatic breast cancer, producing a 22% reduction in risk of
NEW ORLEANSAn international phase III study has found the combination of gemcitabine (Gemzar) plus paclitaxel to be superior to single-agent paclitaxel in the front-line treatment of metastatic breast cancer, producing a 22% reduction in risk of death, according to Kathy S. Albain, MD, professor of medicine, Loyola University, Chicago, who presented the results at the 40th Annual Meeting of the American Society of Clinical Oncology (abstract 510). "The gemcitabine/paclitaxel regimen showed very promising survival vs paclitaxel alone, when given in an every-3-week schedule. I believe the data firmly place gemcitabine/paclitaxel as a new standard treatment," Dr. Albain said.
The study evaluated the gemcitabine/paclitaxel combination in 529 breast cancer patients with no prior treatment in the metastatic setting. Patients were enrolled between August 1999 and April 2002 at 98 study centers in 19 countries.
Patients were randomized to gemcitabine 1,250 mg/m2 on days 1 and 8 plus paclitaxel 175 mg/m2 on day 1 or to paclitaxel 175 mg/m2 on day 1 every 21 days until disease progression.
Preliminary results from this study were presented at ASCO last year (O’Shaughnessy J et al: Proc ASCO 22:7, 2003, abstract 25). At that time, Dr. O’Shaughnessy reported that the combination conveyed significant benefits in terms of time to progression, progression-free survival, objective response rates, and quality of life, without compromising tolerability.
The updated findings added an overall survival benefit to the data reported last year. The analysis was based upon the occurrence of approximately 75% (n = 343) of the deaths needed (n = 440) for the planned final overall survival report, which is expected in early 2005. The median follow-up was 15.6 months.
There were 160 deaths in 267 patients in the combination arm, and 183 in 262 patients treated with paclitaxel alone. Median overall survival rates were 18.5 months and 15.8 months, respectively. One-year survival was 70.7% vs 60.9%, and 18-month survival was 50.7% vs 41.9%. The reduction in risk of death was 22% with the combination (P = .018), Dr. Albain reported. In multivariate analysis, the risk reduction was 26% (P = .006).
Response rates were 40.8% for the combination and 22.1% for single-agent paclitaxel (P < .0001). Median time to progression was 5.2 months vs 2.9 months (P < .0001), and 6-month progression-free survival was 37% vs 23%, respectively (P = .0027). The hazard ratio for time to documented progressive disease was 0.650 (P < .0001), Dr. Albain reported.
On the basis of the time-to-progression and the interim survival data, the US Food and Drug Administration recently approved gemcitabine/paclitaxel for breast cancer patients who progress after prior anthracycline-containing adjuvant chemotherapy, Dr. Albain noted.
Only 7% of the gemcitabine doses had to be omitted, and only 8% had to be reduced because of toxicity. Grade 4 hematologic toxicity was more pronounced with the combination vs the single agent, with grade 4 neutropenia occurring in 17% vs 7%, respectively. Febrile neutropenia occurred in 5% and 1%, while transfusions were given to 10% and 4%, respectively.
Dr. Albain noted that grade 3-4 non-hematologic toxicity was uncommon and predominantly neuropathy and emesis, which was seen at a similar frequency in both arms. Grade 3 fatigue occurred in 6% in the combination arm and 1% in the single-agent arm, with low rates of diarrhea and dyspnea in both arms. One toxic death occurred in each arm.
Joyce O’Shaughnessy, MD, of Baylor-Sammons Cancer Center, Dallas, who presented the interim data last year, commented on the updated findings and the toxicity profile: "These results are extremely encouraging, and it is particularly nice to see this in the face of very little additive toxicity with gemcitabine. This doublet is very well tolerated, which really helps clinicians use it in patients who need combination chemotherapy."