Fruquintinib

The phase III, international, double-blind, placebo-controlled FRESCO-2 trial (NCT04322539) included 691 patients with metastatic colorectal adenocarcinoma who had received all standard approved cytotoxic and targeted therapies. Patients had disease progression during, or were intolerant of, trifluridine-tipiracil, regorafenib, or both. Patients had received a median of four lines of prior systemic therapy. Patients were randomly assigned in a 2:1 fashion to receive one of the following regimens:All patients received best supportive care. A total of 461 patients received fruquintinib, and 230 received placebo. The primary end point was OS.[52] The results were as follows:

The phase III, international, double-blind, placebo-controlled FRESCO-2 trial (NCT04322539) included 691 patients with metastatic colorectal adenocarcinoma who had received all standard approved cytotoxic and targeted therapies. Patients had disease progression during, or were intolerant of, trifluridine-tipiracil, regorafenib, or both. Patients had received a median of four lines of prior systemic therapy. Patients were randomly assigned in a 2:1 fashion to receive one of the following regimens:All patients received best supportive care. A total of 461 patients received fruquintinib, and 230 received placebo. The primary end point was OS.[52] The results were as follows:

Fruquintinib (5 mg orally once daily on days 1–21 of a 28-day cycle).

The phase III, international, double-blind, placebo-controlled FRESCO-2 trial (NCT04322539) included 691 patients with metastatic colorectal adenocarcinoma who had received all standard approved cytotoxic and targeted therapies. Patients had disease progression during, or were intolerant of, trifluridine-tipiracil, regorafenib, or both. Patients had received a median of four lines of prior systemic therapy. Patients were randomly assigned in a 2:1 fashion to receive one of the following regimens:All patients received best supportive care. A total of 461 patients received fruquintinib, and 230 received placebo. The primary end point was OS.[52] The results were as follows:

Placebo (orally once daily on days 1–21 of a 28-day cycle).

The phase III, international, double-blind, placebo-controlled FRESCO-2 trial (NCT04322539) included 691 patients with metastatic colorectal adenocarcinoma who had received all standard approved cytotoxic and targeted therapies. Patients had disease progression during, or were intolerant of, trifluridine-tipiracil, regorafenib, or both. Patients had received a median of four lines of prior systemic therapy. Patients were randomly assigned in a 2:1 fashion to receive one of the following regimens:All patients received best supportive care. A total of 461 patients received fruquintinib, and 230 received placebo. The primary end point was OS.[52] The results were as follows:

The median OS was significantly longer in the fruquintinib group (7.4 months; 95% CI, 6.7–8.2) than in the placebo group (4.8 months; 95% CI, 4.0–5.8) (HR, 0.66; 95% CI, 0.55–0.80; P < .0001).[52][Level of evidence A1]

The phase III, international, double-blind, placebo-controlled FRESCO-2 trial (NCT04322539) included 691 patients with metastatic colorectal adenocarcinoma who had received all standard approved cytotoxic and targeted therapies. Patients had disease progression during, or were intolerant of, trifluridine-tipiracil, regorafenib, or both. Patients had received a median of four lines of prior systemic therapy. Patients were randomly assigned in a 2:1 fashion to receive one of the following regimens:All patients received best supportive care. A total of 461 patients received fruquintinib, and 230 received placebo. The primary end point was OS.[52] The results were as follows:

The median PFS was 3.7 months (95% CI. 3.5–3.8) in the fruquintinib group and 1.8 months (95% CI, 1.8–1.9) in the placebo group (HR, 0.26; 95% CI, 0.21–0.34; P < .001).

The phase III, international, double-blind, placebo-controlled FRESCO-2 trial (NCT04322539) included 691 patients with metastatic colorectal adenocarcinoma who had received all standard approved cytotoxic and targeted therapies. Patients had disease progression during, or were intolerant of, trifluridine-tipiracil, regorafenib, or both. Patients had received a median of four lines of prior systemic therapy. Patients were randomly assigned in a 2:1 fashion to receive one of the following regimens:All patients received best supportive care. A total of 461 patients received fruquintinib, and 230 received placebo. The primary end point was OS.[52] The results were as follows:

Subgroup analyses demonstrated the benefit of fruquintinib as opposed to placebo in most subgroups. Notably, this benefit was seen in patients with both RAS variants and RAS wild-type disease, patients with liver metastases, and patients pretreated with trifluridine-tipiracil with or without regorafenib.

The phase III, international, double-blind, placebo-controlled FRESCO-2 trial (NCT04322539) included 691 patients with metastatic colorectal adenocarcinoma who had received all standard approved cytotoxic and targeted therapies. Patients had disease progression during, or were intolerant of, trifluridine-tipiracil, regorafenib, or both. Patients had received a median of four lines of prior systemic therapy. Patients were randomly assigned in a 2:1 fashion to receive one of the following regimens:All patients received best supportive care. A total of 461 patients received fruquintinib, and 230 received placebo. The primary end point was OS.[52] The results were as follows:

The disease control rate was significantly longer in the fruquintinib group (56%) than in the placebo group (16%), with an adjusted difference of 39% (95% CI, 32.8%–46.0%; P < .0001).

The phase III, international, double-blind, placebo-controlled FRESCO-2 trial (NCT04322539) included 691 patients with metastatic colorectal adenocarcinoma who had received all standard approved cytotoxic and targeted therapies. Patients had disease progression during, or were intolerant of, trifluridine-tipiracil, regorafenib, or both. Patients had received a median of four lines of prior systemic therapy. Patients were randomly assigned in a 2:1 fashion to receive one of the following regimens:All patients received best supportive care. A total of 461 patients received fruquintinib, and 230 received placebo. The primary end point was OS.[52] The results were as follows:

Grade 3 or higher adverse events occurred in 65% of patients in the fruquintinib group. The most common adverse events were hypertension (14%), asthenia (8%), abnormal hepatic function (8%), dermatologic toxicity (7%), and hand-foot syndrome (6%). Grade 3 or higher adverse events occurred in 50% of patients in the placebo group. The most common were abnormal hepatic function (9%), infection (6%), and asthenia (4%).