Molecular insights
Although correlative analyses of tumor tissue and peripheral blood are embedded in the DART trial, those analyses have not yet been performed. Eight of the 16 angiosarcoma patients had diagnostic molecular studies performed at their parent institutions, utilizing a variety of commercial platforms.
Dr. Alan P. Lyss
All eight patients for whom molecular data were available had at least two deleterious genomic alterations detected, but each had a distinct molecular profile.
Seven patients had TMB analyzed, including two partial responders to ICB. One of the seven patients had a high TMB, and this patient was one of the two responders. The other responder had an intermediate TMB.
Three patients had programmed death–ligand 1 staining on their tumors. Two of the three had high expression of PD-L1, including the responder with an intermediate TMB.
The real impact of DART
The DART trial is a “basket trial,” employing a similar treatment regimen for multiple tumor types. It provides a uniform framework for studying tumors that have been neglected in clinical trials heretofore.
Although the cohort of angiosarcoma patients is small, central pathology review was not required, and the treatment regimen was not compared directly with other potential therapies, the reported results of the ipilimumab-nivolumab regimen justify further study.
The biospecimens collected in DART will provide a rich source of data to identify common themes among responders and nonresponders, among patients who experience durable remissions and those who do not.
Angiosarcoma is not the only rare cancer for which combinatorial ICB has been valuable under the auspices of the DART trial. In Clinical Cancer Research, investigators reported an ORR of 44% among patients with high-grade neuroendocrine cancers, independent of primary site of origin. Progression-free survival at 6 months was 31%.
The DART trial is available at more than 800 sites, providing access to potentially promising treatment in a rigorous, scientifically valuable study for geographically underserved populations, including patients who live in rural areas.
The key message for practicing oncologists and clinical investigators is that clinical trials in rare tumors are feasible and can yield hope for patients who might lack it otherwise.
DART is funded by the National Cancer Institute and Bristol-Myers Squibb. Dr. Wagner disclosed relationships with Deciphera, Adaptimmune, GlaxoSmithKline, Athenex, and Incyte.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
SOURCE: Wagner M et al. SITC 2020, Abstract 795.