FISH-Guided Therapy Balances Clinical Benefits and Cost

Charles Bankhead

February 2011, Vol 2, No 1 -

San Antonio, TX—Treatment of recurrent metastatic breast cancer based on reassessment of HER2 status offers the optimal combination of clinical effectiveness and cost, based on 6 different clinical strategies.

The largest gain in quality-adjusted life-years (QALYs) with an acceptable incremental cost occurred with a strategy of retesting tumors by fluorescence in situ hybridization (FISH) and giving trastuzumab only to patients with positive tests.

A treatment strategy based on positive results with both immunohistochemistry (IHC) staining and FISH also resulted in a balance between effectiveness and cost.

“It is interesting to notice that the strategy of no retesting on recurrence— probably the most common one used in clinical practice—is dominated and thus suboptimal,” Mattias Bernow, MD, of Karolinska Institute in Stock holm, reported at the San Antonio Breast Cancer Symposium.

FISH Tops Smorgasbord of Strategies
In as many as 30% of cases of recurrent metastatic breast cancer, the HER2 status of the tumor has changed. How ever, most physicians base their decisions about anti-HER2 therapy with trastuzumab on the HER2 status of the primary tumor, Dr Bernow and colleagues noted in a poster presentation.

The clinical value and cost of reevaluating HER2 status on recurrence remain unclear. To evaluate those issues, Dr Bernow and colleagues used a Markov state transition model to simulate 6 different strategies for retesting HER2 status and use of trastuzumab:
No retesting and use of chemotherapy alone for all patients
No retesting and use of trastuzumab in patients with HER2-positive primary tumors
Retesting with IHC, giving tras tuzumab to patients who test IHC 3+
Retesting with IHC and giving trastuzumab to IHC 2+ and 3+ patients
Retesting with IHC, follow-up FISH testing for IHC 2+ or 3+ tumors, and trastuzumab for FISH+ tumors
Retesting with FISH and trastuzu – mab for all FISH+ patients.

The strategies were evaluated in patient cohorts: one based on treatment guidelines and published data and the other derived from actual patient records in a Swedish breast cancer database.

Of the various strategies, a strategy of retesting with FISH and giving trastuzumab to FISH+ patients resulted in a gain of 1.543 QALYs, at costs of $59,500 and $55,400, respectively, and incremental cost-effectiveness ratios (ICERs) of $75,500 and $73,300, respectively, for the guideline and actualpatient cohorts.

A strategy of retesting with IHC, FISH for IHC 2+ or 3+, and trastuzumab plus chemotherapy for FISH+ patients yielded a gain of 1.525 QALYs.

The improvement was associated with a cost of $58,100 and ICER of $63,200 in the guideline cohort and a cost of $54,100 and ICER of $61,100 in the actual-patient cohort.

“A previous Swedish study estimated willingness to pay of $88,900 per QALY gained,” Dr Bernow and colleagues noted. “Thus, retesting of HER2 status of recurring breast cancer patients is clinically relevant and costeffective.”