The Journal of Clinical Oncology has featured a study which evaluated whether patients with intolerable toxicity from one aromatase inhibitor (AI) are able to tolerate another. A total of 503 women with early-stage breast cancer initiating AI therapy were enrolled onto a multicentre, prospective, open-label randomised trial of exemestane versus letrozole. Patients who developed AI-associated intolerable symptoms and discontinued treatment were given the option to switch to the other study AI after a 2- to 8-week washout period.

The following results were reported:

• Analysis of the 500 eligible patients revealed that 163 patients (32.6%) discontinued therapy because of adverse effects: 91 patients (36.7%) randomly assigned to exemestane, and 72 patients (28.6%) randomly assigned to letrozole discontinued therapy because of at least one treatment-emergent symptom, a difference that was statistically significant (P=0.02).

• Median time to treatment discontinuation as a result of development of symptoms was 6.1 months (range, 0.1 to 21.2 months). Median time to treatment discontinuation as a result of development of symptoms was 5.8 months (range, 0.2 to 20.3 months) for patients assigned to exemestane and 8.1months (range, 0.1 to 21.2 months) for patients assigned to letrozole. Time to treatment discontinuation as a result of any symptom was significantly shorter in patients randomly assigned to exemestane compared with letrozole (HR, 1.5;95%CI, 1.1 to 2.1; P=0.02)

Because the option to cross over from the first to the second AI as a result of toxicity was added in an amendment, only the 368 patients who enrolled after the amendment was approved at the individual sites were eligible for the cross-over analysis.

• Of the evaluable cross-over cohort, 128 patients (34.8%) discontinued initial AI therapy because of intolerable symptoms after a median of 6.1 months (range, 0.2 to 21.2 months). Of those, 83 patients (63.8%) chose to cross over to the other drug, whereas the remainder chose to discontinue AI therapy and study participation. Forty-nine patients (26.8%) initially treated with exemestane switched to letrozole, whereas 34 patients (18.4%) initially treated with letrozole switched to exemestane.

• Of the 83 patients who crossed over to the second AI, 51 (61.4%) discontinued the second AI medication after a median of 3.5 months (range, 0.2 to 27.8 months), 34 (66.7%) of whom discontinued therapy because of musculoskeletal symptoms.

• More of the patients originally treated with letrozole (23 of 34 patients, 67.6%) discontinued exemestane after cross over, compared with the reverse (28 of 49 patients, 57.1%), although this difference was not statistically significant.

The researchers concluded that “more than one third of patients who switch drugs may tolerate the second AI. Additional biochemical and genetic studies designed to refine existing predictors of these adverse effects for individual patients are warranted. A better understanding of the mechanisms underlying development of AI-associated toxicities is important, because this could yield clues to more accurate predictors of development of toxicity and guide future interventional symptom prevention or management strategies. Overall, this additional information may help improve tolerance of the medications, thereby improving quality of life and persistence with therapy and, by extension, breast cancer outcomes.”