In a discussion following the presentation, Lars M. Wagner, MD, of Cincinnati Children’s Hospital, pointed out that the study was not powered for the PFS and OS assessments. These were secondary objectives that should be considered exploratory. Therefore, he said, the outcome data is not conclusive. The role of temozolomide in RMS is also unclear, given recent negative results in patients with newly diagnosed metastatic RMS (Malempati et al, Cancer 2019). And he said it’s uncertain how these results apply to patients who received irinotecan upfront for RMS.
SOURCE: Defachelles AS, et al. J Clin Oncol 37, 2019 (suppl; abstr 10000)
The study was sponsored by Centre Oscar Lambret and SFCE (Société Française de Lutte contre les Cancers et Lucémies de l’Enfant et de l’Adolescent) served as collaborator.
Drs. Defachelles and Wagner had no relationships to disclose. A few coauthors had advisory/consulting or speaker roles for various commercial interests, including two for Merck (temozolomide).
Pazopanib Increases Pathologic Necrosis Rates in STS
Pazopanib added to a regimen of preoperative chemoradiation in non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) significantly increased the rate of near-complete pathologic response in both children and adults with intermediate or high-risk disease. Pazopanib, a multitargeted receptor tyrosine kinase inhibitor, works in multiple signaling pathways involved in tumorigenesis— VEGFR-1, -2, -3, PDGFRα/β, and c-kit. A phase 3 study demonstrated significant improvement in progression-free survival (PFS) in advanced STS patients and was the basis for its approval in the US and elsewhere for treatment of this patient population. Preclinical data suggest synergy between pazopanib and cytotoxic chemotherapy, forming the rationale for the current trial with neoadjuvant pazopanib added to chemoradiation.
According to the investigators, the trial (ARST1321) is the first ever collaborative study codeveloped, written, and conducted by pediatric (Children’s Oncology Group) and adult (NRG Oncology) cancer cooperative groups (NCT02180867). Aaron R. Weiss, MD, of the Maine Medical Center in Portland and study cochair, presented the data for the chemotherapy arms at ASCO. The primary objectives of the study were to determine the feasibility of preoperative chemoradiation with or without pazopanib and to compare the rates of complete pathologic response in patients receiving radiation or chemoradiation with or without pazopanib. Pathologic necrosis rates of 90% or better have been found to be predictive of outcome in STS.