Number needed to treat/harm (NNT/NNH): A benefit/risk analysis of fruquintinib vs other treatments for metastatic colorectal cancer (mCRC).

Abstract

126 Background: NNT/NNH analyses can estimate the magnitude of benefit vs harm of therapeutic agents and can inform clinical decision making. We quantified the benefit/risk profile of fruquintinib (F; a highly selective, oral inhibitor of all 3 VEGFRs) vs other later-line mCRC monotherapies. Methods: Six phase 3 randomized (2:1), placebo (P)-controlled trials (F: FRESCO, FRESCO-2; regorafenib [rego]: CONCUR, CORRECT; TAS-102: TERRA, RECOURSE) were identified. NNT (average number of pts needing treatment to prevent 1 additional death/progression event) for overall survival (OS) and progression-free survival (PFS) was calculated as the inverse of difference in survival function between treatment and P. NNH (average number of pts needing treatment for 1 additional pt to have an adverse event; AE) for treatment-emergent AEs (TEAEs) was calculated as the inverse of absolute risk increase relative to P. Low NNTs and high NNHs suggest a more favorable treatment profile. Results: F had the lowest NNT (most favorable) for 6-month OS (FRESCO-2) and PFS (FRESCO) vs rego and TAS-102 (Table). F had the highest NNH (most favorable) for grade ≥3 TEAEs, palmar-plantar erythrodysesthesia (PPE; FRESCO-2), and fatigue (FRESCO). TAS-102 (TERRA) had the highest NNH for diarrhea, followed by F (FRESCO-2). Consistent with mechanism of action of anti-VEGFRs, F and rego had lower NNHs for hypertension (HTN) vs TAS-102 (TERRA). F (FRESCO) had the lowest NNH for discontinuation due to TEAEs. Conclusions: In this cross-trial comparison, F had the lowest NNT for OS (FRESCO-2) and PFS (FRESCO/FRESCO-2), indicating survival benefit. F had the highest NNHs for grade ≥3 TEAEs, PPE (FRESCO-2), and fatigue (FRESCO), indicating a low risk profile. The analysis highlights fruquintinib as a favorable treatment for pts with mCRC. Clinical trial information: NCT02314819 , NCT04322539 , NCT01584830 , NCT01103323 , NCT01955837 , NCT01607957 . NNT/NNH (95% CI) for mCRC treatments.* F Rego TAS-102 FRESCO NCT02314819 N=416 FRESCO-2 NCT04322539 N=691 CONCUR NCT01584830 N=204 CORRECT NCT01103323 N=760 TERRA NCT01955837 N=406 RECOURSE NCT01607957 N=800 6-month OS 6.5(5.5–8.1) 5.3(4.8–5.9) 5.9(NA) 9.8(NA) 14.1(NA) 7.2(NA) 6-month PFS 4.2(3.7–4.8) 4.4(3.9–5.1) 5.0(NA) 9.1(NA) 7.1(NA) 7.2(NA) Grade ≥3 TEAEs 2.4 (2.0–3.1) 8.1 (5.0–22.5) 2.6 (2.0–3.7) 2.5 (2.2–3.0) 2.8 (2.3–3.6) 5.9 (4.1–10.2) TEAE leading to discontinuation 10.8 (6.7–28.5) NA † (18.0–NA) 12.5 (6.2–NA) 17.5(11.3–39.2) 250.0 (15.3–NA) 50.0 (22.9–NA) PPE 2.2 (1.9–2.5) 6.0 (4.8–8.0) 1.4 (1.3–1.7) 2.6 (2.2–3.0) NA (NA) NA (46.0–NA) HTN 2.4 (2.0–3.0) 3.6 (3.0–4.5) 5.3 (3.6–9.5) 4.5 (3.7–5.8) 14.3 (10.0–25.2) NA (NA) Diarrhea 5.1 (3.8–7.4) 7.3 (5.2–12.3) 6.2 (4.3–11.4) 3.8 (3.2–4.8) 7.9 (5.7–13.0) 5.0 (3.9–6.9) Fatigue 32.5 (10.3–NA) 25.8 (10.1–NA) 10 (5.3–80.3) 5.3 (3.8–8.4) 7.4 (5.0–13.9) 8.3 (5.4–18.1) *All trials except TERRA included best supportive care in both arms. † Lower rate of pts discontinued F vs P due to TEAEs, thus NNH was not applicable (NA).