HER2+ BC: A Year in Review and Updates from SABCS - Episode 7

Disease-Free Interval and Overall Survival in HER2+ BC

Analysis from the ALTTO (BIG 2-06) trial and the relationship between a short or long disease-free interval and overall survival.

Hatem Soliman, MD: Another area of investigation for early stage disease to discuss a little further is talking about the prognostic distant disease-free survival [DFS] interval from the completion of adjuvant trastuzumab for early stage disease. This was an update from the ALTTO study.

Andrew Seidman, MD: ALTTO was an adjuvant trial to see if lapatinib could improve outcomes in patients getting adjuvant chemotherapy. Patients were randomized to a year of trastuzumab, a year of lapatinib, a year of the combination of trastuzumab or lapatinib, or the sequential use of trastuzumab followed by lapatinib. We know this trial did not lead to any adjuvant indication for lapatinib, and what was analyzed was the relationship between a short or a long disease-free interval [DFI] and overall survival.

The result was intuitive. There were 404 distant disease-free survival events, and they were just about evenly split with the dichotomous variable of 12 months for disease-free interval. Those patients relapsing less than 12 months tended to be older, have an increase in tumor size, and to be ER [estrogen receptor] negative. But their overall survival was 18.4 months, and the patients relapsing more than 12 months from completion of their adjuvant therapy had an overall survival of 29.3 months. It was 11 months longer for patients who relapsed more than a year from completion therapy. If your DFS is shorter, it says something about the intrinsic biology of your disease and the course of your time with metastatic breast cancer parallels.

There was a higher incidence of brain metastasis in those patients relapsing less than 12 months. There was a 26% rate of brain metastasis in that group vs 15% in patients relapsing more than a year. But because you don’t know who’s going to relapse at all, never mind less than a year or greater than a year, it was interesting work: We are not sure how it’s going to impact practice, but it argues that patients with short relapse need more aggressive approaches, short relapse-free intervals.

Hatem Soliman, MD: We teach our fellows and our students in clinic to pay attention to those DFIs for gauging the nature of the disease relapse. It does play a role in terms of subsequent treatment selection, what we determine they’re probably refractory to vs what we’ll give them a shot on. It will be interesting as the agents work their way earlier in the treatment algorithm, now with some of these novel agents that could overcome these resistant phenotypes, after therapy.

Andrew Seidman, MD: The result should motivate the migration of tyrosine kinase inhibitors earlier in the treatment algorithm, primarily because of the potential CNS [central nervous system] effect and non-CNS effects.

Transcript edited for clarity.