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    • A previous review article suggested different

    2024-05-15

    A previous review article suggested different washout intervals based on specific clinical contexts [4]. While no consensus was reached for the optimal interval between last dose of BV and surgery for CRLM, the authors of the review suggested waiting 6 to 8 weeks after BV before surgery, particularly before major surgical procedures, including hepatic and colorectal resections and the equivalent. In the postoperative and adjuvant CRC setting, most patients could likely start treatment with BV after 28 days, but in patients with comorbid conditions or wound healing issues, an interval of 6 to 8 weeks may be more appropriate. We agree with these suggestions and typically discontinue BV for 6 to 8 weeks before surgery for mCRC and wait 28 days after surgery prior to initiating adjuvant BV, assuming there are no wound healing issues. Effects of neoadjuvant BV on outcomes related to breast surgery are undetermined, and the authors recommended that BV should be discontinued at least 28 days before surgery. Because wound dehiscence is a particular concern for patients with CNS tumors (previous radiotherapy and frequent, prolonged corticosteroid use also increases this Benzethonium Chloride risk), the authors suggested waiting on VEGF-targeted therapy for 2 to 4 weeks after stereotactic biopsy and 4 to 6 weeks after craniotomy. In RCC, trials typically waited 4 weeks between VEGF-targeted therapy and surgery, with no reports of delayed wound healing. While there are no published recommendations on the appropriate time interval between VEGF-targeted therapy and pulmonary resection, the authors of the prior review suggested waiting 4 weeks before low-risk pulmonary resections (eg, wedge resections or simple lobectomies) and 6 to 8 weeks for more complex procedures (eg, chest-wall or bronchoplastic-sleeve resections). These washout intervals seem reasonable based on our experience. Recommendations for optimal surgical timing after and/or before bevacizumab are summarized in Table 2.
    Additional safety data for antiangiogenic agents across oncology indications Beyond surgical complications, antiangiogenic agents are associated with many other AEs, some of which are serious and can be life threatening and thus are worthy of mention. In a recent review article of BV across tumor types, the most common AEs included hypertension, fatigue or asthenia, diarrhea, abdominal pain, and bleeding (most commonly epistaxis) [58]. Less common events attributed to BV were proteinuria, wound healing complications, severe hemorrhage, gastrointestinal perforation, and arterial thromboembolic events. A review of the incidence of bowel perforations with BV across a variety of metastatic cancers reported rates of 1–2% in CRC, 0–11% in ovarian cancer, ∼1% in breast cancer, 0–1% in NSCLC, and 0–8% in CNS tumors [59]. A meta-analysis of 33 RCTs (26,833 patients) evaluating BV across advanced cancers demonstrated a significantly increased risk overall of gastrointestinal perforations with BV-containing regimens (relative risk, 3.35; 95% CI, 2.35–4.79; P < 0.001) [60]. Increased risks of perforations with BV-containing therapy were also significant for the subgroups of CRC (relative risk, 2.84; 95% CI, 1.43–5.61; P = 0.003), gynecologic cancers (relative risk, 3.37; 95% CI, 1.71–6.62; P < 0.001), and prostate cancer (relative risk, 6.01; 95% CI, 1.78–20.28; P = 0.004) [60]. While less clinical data are available for ramucirumab, a recently approved anti-VEGFR2 monoclonal antibody, a recent meta-analysis of phase II/III trials reported fatigue, neutropenia, bleeding, nausea, and stomatitis as the most common AEs [61]. The most frequent grade ≥3 AEs with ramucirumab were neutropenia, fatigue, leukopenia, hypertension, and liver injury [61]. An analysis of patients from 6 placebo-controlled phase III trials of ramucirumab across multiple tumor types (4996 patients) suggested acid there was no increased risk of arterial thromboembolic events, venous thromboembolic events, high-grade bleeding and high-grade gastrointestinal bleeding [62]. However, ramucirumab was associated with higher rates of hypertension, proteinuria, low-grade bleeding, gastrointestinal perforation and wound-healing complications versus the control arm [62].