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Addition of TKIs to chemotherapy extended PFS, increased toxicity in solid cancers
The addition of tyrosine kinase inhibitors to chemotherapy modestly improved PFS among patients with solid cancers, but it also increased the risk for treatment discontinuation and fatal or severe events, according to results of a meta-analysis.
Researchers reviewed PubMed and ASCO databases to identify 43 randomized controlled trials that evaluated VEGFR- or EGFR-targeted TKIs plus chemotherapy vs. chemotherapy alone. The trials included 16,011 patients with any solid cancer.
Overall, patients assigned TKIs plus chemotherapy demonstrated modestly improved PFS (HR=0.82; 95% CI, 0.76-0.89). However, the combination was not associated with extended OS (HR=0.99; 95% CI, 0.95-1.03).
The combination of TKIs plus chemotherapy was linked to an increased risk for fatal adverse events (RR=1.63; 95% CI, 1.32-2.01), as well as grade 3 or grade 4 adverse events (RR=1.25; 95% CI, 1.16-1.36), compared with chemotherapy alone.
Patients assigned TKIs plus chemotherapy also were more likely to discontinue study treatment (RR=1.8; 95% CI, 1.58-2.06) compared with patients assigned chemotherapy alone.
“The approach of combining cytotoxic chemotherapy with oral small-molecule TKIs has been explored in a large number of randomized trials, in a variety of tumors,” the researchers wrote. “It is important for physicians to weigh the risk of toxicity vs. the modest PFS benefit associated with chemotherapy plus TKI in patients with solid cancers.”
Disclosure: See the study for a full list of the researchers’ relevant financial disclosures.