medwireNews: The addition of indoximod to taxane chemotherapy does not improve the outcomes of patients with HER2-negative metastatic breast cancer, research suggests.
The indoleamine 2,3-dioxygenase 1 (IDO1) pathway inhibitor indoximod demonstrated a “promising” efficacy and safety profile in early trials among patients with metastatic solid tumors, say Hatem Soliman (H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA) and fellow researchers in JAMA Oncology.
They note, however, that the current phase 2 double-blind trial “was prematurely discontinued in June 2017 owing to lack of efficacy.”
Indeed, after a median 17.4 months of follow-up, the primary endpoint of progression-free survival (PFS) did not differ significantly between the 85 patients who were randomly assigned to receive indoximod 1200 mg twice daily with docetaxel or paclitaxel and the 79 patients who instead received placebo plus a taxane, at a median of 6.8 and 9.5 months, respectively.
There were also no significant between-group differences in median overall survival (19.5 vs 20.6 months) or objective response rate (40 vs 37%).
“Overall, the combination was manageable,” note the researchers, with treatment-emergent adverse events (TEAEs) of grade 3 or worse observed in a comparable 60.0% of indoximod-treated patients and 60.8% of those given placebo.
The most common grade 3 or higher AEs in the indoximod versus placebo groups were neutropenia (9.4 vs 17.7%), anemia (8.2 vs 3.8%), fatigue (7.1 vs 5.1%), and abdominal pain (4.7 vs 1.3%).
TEAEs led to treatment discontinuation in 12.9% and 12.7% of patients in the indoximod and placebo arms, respectively, while the corresponding rates of TEAE-related deaths were 4.7% and 2.5%.
The results of an exploratory biomarker analysis suggested “a trend towards inferior outcomes in IDO1-low patients,” say the researchers, but they caution that “this may be due to an imbalance in patients with adverse prognosis within the analyzed patients as opposed to the IDO1 status itself.”
Soliman et al therefore conclude that “[a]dditional biomarker research is needed to indicate which patients would benefit more from IDO1 inhibitors or IDO1/[tryptophan 2,3-dioxygenase] combinations.”
They add: “Expression of IDO1 should be investigated further as a biomarker in future prospective studies of IDO1 inhibitors.”
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