Victoria Wang

Supplementary Tables including study representativeness table.

Purpose: Mutations in BRAF at codons other than V600 (non-V600) and BRAF fusions confer dependence on the RAF–MEK–ERK pathway. Subprotocol Z1L (EAY131-Z1L) investigated the clinical activity of ulixertinib (ERK1/2 inhibitor) in patients with tumors harboring these alterations. Patients and Methods: In this single-arm study, patients with BRAF non-V600 mutations or BRAF fusions were given ulixertinib orally, at a dose of 600 mg twice daily, continuously for each 28-day cycle until progression or intolerability. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), 6-month PFS, and overall survival (OS). Results: Of the 34 eligible patients, the median age was 66.5; 50% were women; and 88%, 9%, and 3% were White, Black, and Asian, respectively. Seventy-four percent of patients had an Eastern Cooperative Oncology Group performance status of 1. The median number of prior therapies was 4. Tumor types included multiple gastrointestinal malignancies (n = 16), lung cancer (n = 3), and melanoma (n = 3). No patients achieved complete response or partial response, resulting in an ORR of 0%. Stable disease was the best response in 7 of 26 centrally confirmed cases. The median PFS was 1.7 months [90% confidence interval (CI), 1.1–2.2]; the 6-month PFS rate was 5% (90% CI, 0.6%–17.7%); and the median OS was 3.5 months (90% CI, 1.9–5.4). Twenty (57%) patients had grade 3 toxicity, and 1 (3%) patient had grade 4 toxicity as their worst toxicity; there was no grade 5 toxicity. Conclusions: Ulixertinib had no demonstrable evidence of clinical activity in this small, heavily pretreated population of patients with tumors harboring BRAF fusions or non-V600E/non-V600K BRAF mutations.

External validation of MI Clarity M3T for late DR in the TAILORx translational cohort. A, Kaplan–Meier analysis of late DR comparing MI Clarity M3T risk groups in all patients. B, Multivariable Cox analysis assessing the independent prognostic value of the MI Clarity M3T risk label, adjusted for clinical covariates. C, Kaplan–Meier analysis of late DR comparing MI Clarity M3T risk groups in arms B and C (ITT). LDR, late distant recurrence.

Effect of ELT on DR across subgroups in the NSABP B-42 translational cohort.

Clinicopathologic, and treatment characteristics of patients classified as MI Clarity–High versus Low risk in the NSABP B-42 translational cohort.

External validation of MI Clarity M3T for overall distant recurrence (DR) in the TAILORx translational cohort.

Clinicopathologic, and treatment characteristics of patients classified as MI Clarity–High versus Low risk in the TAILORx translational late-DR cohort.

Kaplan–Meier analysis of DR comparing patients treated with ELT vs. placebo in the NSABP B-42 translational cohort. A, All patients. B, Low-risk group. C, High-risk group. High- and low-risk groups are defined by the M3T model.

Kaplan–Meier analysis of DR in the NSABP B-42 translational cohort according to MI Clarity M3T risk groups. A, All patients. B, ELT-treated group. C, Placebo group. High- and low-risk groups are defined by the M3T model.

Time-dependent predictive performance of the M3T model for ELT benefit in clinical subgroups with violated proportional hazards (PH) assumption.