SAN ANTONIO – Adjuvant chemotherapy in women with completely resected locoregional recurrence of breast cancer improved disease-free and overall survival in the randomized CALOR trial.
Indeed, adjuvant chemotherapy reduced the risk of recurrent disease by 41% during 5 years of follow-up in CALOR (Chemotherapy as Adjuvant for Locally Recurrent Breast Cancer) while cutting the risk of all-cause mortality by 59%, Dr. Stefan Aebi reported at the annual San Antonio Breast Cancer Symposium.
Thus, CALOR helps resolve a longstanding controversy regarding the appropriate treatment of patients with isolated local or regional recurrence of breast cancer. But the trial provides only a partial resolution. That’s because while adjuvant chemotherapy had a huge benefit in patients with estrogen receptor–negative locoregional recurrences, in estrogen receptor–positive recurrences it had no significant effect.
"Decisions regarding ER-positive recurrent tumors remain a struggle. But events are very few so far. We consider this analysis premature. We will need longer follow-up for patients with ER-positive recurrences to see if there is a benefit for chemotherapy," said Dr. Aebi, head of the division of medical oncology at Lucerne Canton Hospital in Switzerland.
CALOR included 162 patients with isolated local and/or regional recurrence of breast cancer. After complete excisional surgery, they were randomized to chemotherapy or no chemotherapy. The choice of chemotherapy regimen was left to the patient’s oncologists, with a recommendation from CALOR investigators to use at least two drugs for 3-6 months. Radiation therapy was recommended for all patients, but only about 40% received it.
The 5-year disease-free survival rate – the primary endpoint – was 69% in the chemotherapy group compared with 57% with no adjuvant chemotherapy. This translates to a 41% relative risk reduction (P = .045). The 5-year overall survival rate was 88% in the chemotherapy group vs. 76% in controls, for a 59% reduction in risk (P = .02).
These benefits were driven by the outstanding effectiveness of chemotherapy in patients with ER-negative recurrences. Their 5-year disease-free survival rate was 67% with adjuvant chemotherapy compared with 35% without it, for a 68% reduction in risk (P = .007). Overall survival in the ER-negative recurrence subgroup was 79% with chemotherapy and 69% without. In contrast, the 5-year disease-free survival rate in the ER-positive group was 70% with chemotherapy and 69% without.
In a multivariate analysis controlling for ER status, location of the isolated recurrence, and prior chemotherapy, adjunctive chemotherapy was associated with a 50% reduction in recurrent disease during 5 years of follow-up (P = .01). The only other independent predictor of disease-free survival was time since primary surgery: The risk of recurrent disease during 5 years of follow-up dropped by 9% for each year since primary surgery.
This was a difficult study to conduct. The original plans called for recruitment of nearly 1,000 patients, but enrollment was so slow that Dr. Aebi and coinvestigators had to scale back their ambitions, eventually closing the trial with 162 participants.
"There were many colleagues with preconceived ideas. We had colleagues who just knew that chemotherapy was not needed and others who just knew that it was needed. And if you know, why should you randomize your patients?" he explained.
Dr. Carlos L. Arteaga called CALOR "a very important contribution to what has been an ongoing controversy in this field."
"Some surgeons feel very strongly that resection is enough in treating local recurrences, while many of our medical oncologists feel chemotherapy is also required. I have a lot more impetus to give adjuvant chemotherapy based on the CALOR findings," said Dr. Arteaga, director of the breast cancer program at Vanderbilt-Ingram Cancer Center, Nashville, Tenn.
The CALOR trial was sponsored by several major cancer research organizations. Dr. Aebi reported having no financial conflicts.