AI-induced symptoms don’t predict survival

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Toxicity doesn’t reflect efficacy

The notion that toxicity related to treatment can be a surrogate for treatment efficacy has long been embedded in the psyche of patients. Oncologists also can mistakenly believe that with cancer, which warrants the most aggressive possible therapy, the strength of a treatment is reflected in the adverse effects it produces.

Dr. William J. Gradishar

But toxicity must not be considered an automatic surrogate measure of clinical benefit. Much of cancer treatments’ toxicity results from collateral damage: nontargeted effects to normal tissue that may or may not share features of the target cancer cell.

Dr. William J. Gradishar is at Northwestern University, Chicago. His financial disclosures are available at Dr. Gradishar made these remarks in an editorial accompanying Dr. Stearns’s report (J. Clin. Oncol. 2014 Dec. 15 [doi:10.1200/JCO.2014.59.0919]).



Vasomotor and musculoskeletal symptoms associated with aromatase inhibitor adjuvant therapy do not signal a more intense treatment response and thus do not predict better survival in women with breast cancer, according to a report published online Dec. 15 in Journal of Clinical Oncology.

Even though several retrospective exploratory analyses have suggested that treatment-emergent symptoms may be associated with improved survival in this patient population, this secondary analysis of data in a large international prospective randomized clinical trial argues otherwise. “It is premature to counsel patients on whether to continue or change their adjuvant AI therapy based on symptoms,” said Dr. Vered Stearns of the Kimmel Cancer Center, Johns Hopkins University, Baltimore, and her associates.

To investigate whether adverse effects might be useful in informing treatment decisions, the investigators analyzed data from the NCIC Clinical Trials Group MA.27 trial – an open-label phase III study conducted in 2003-2008 and involving 7,567 postmenopausal women who had hormone receptor–positive breast cancer. After completing their initial treatment and a washout period to allow for any adverse effects related to it, these participants were randomly assigned to receive adjuvant therapy with either anastrozole (3,787 women) or exemestane (3,789 women) and followed for a median of 4 years. To collect treatment-related symptoms in a standardized manner, they completed Common Terminology Criteria for Adverse Events questionnaires at baseline and at regular intervals afterward.

A relatively high number of these participants (34%) reported already having such symptoms at baseline, which may reflect rebound symptoms from hormone therapy withdrawal during the washout period. For women who had no symptoms at baseline, 25% reported them at 6 months and 52% reported them by 12 months.

At 3-month follow-up, 96 of the 403 women with severe symptoms discontinued treatment; the rate of treatment discontinuation was 12% at 6 months and 10% at 12 months. The most common reason cited for discontinuation was joint pain.

The emergence of new or worsening vasomotor and musculoskeletal symptoms showed no association with recurrence-free survival. There was no correlation between recurrence-free survival and symptoms at baseline or symptoms induced by AI therapy at 3 months, 6 months, or 12 months in the overall study population or in any subgroup of patients, Dr. Stearns and her associates said (J. Clin. Oncol. 2014 Dec. 15 [doi:10.1200;JCO.2014.57.6926]).

These findings indicate that treatment-emergent symptoms should be managed as effectively as possible but not held up as evidence that adjuvant therapy is working. “Women should be supported through treatment and encouraged to remain on their AI regardless of their symptoms,” the investigators added.

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