Applying the local anesthetic lidocaine preceding surgery yielded significant survival benefits for patients with early-stage breast cancer.
Peritumoral application of the local anesthetic lidocaine preceding surgery resulted in significant survival benefits compared with surgery alone for patients with early-stage breast cancer, according to findings from a phase 3 trial (NCT01916317) published in the Journal of Clinical Oncology.1
Results from the trial showed that, at a median follow-up of 68 months (range, 0.5-72), there were 109 disease-free survival (DFS) events in the lidocaine arm (n = 786) and 146 events in the surgery-only arm (n = 797). Seventy-nine patients in the lidocaine arm died compared with 110 patients in the surgery-only arm. The 5-year DFS rates among surviving patients were 86.6% and 82.6%, respectively (HR, 0.74; 95% CI, 0.58-0.95; P = .017). Additionally, the 5-year overall survival (OS) rates were 90.1% vs 86.4%, respectively (HR, 0.71; 95% CI, 0.53-0.94; P = .019).1
“Peritumoral injection of 0.5% lidocaine before surgery offered a clinically meaningful improvement in DFS and OS with relative risk reductions of 26% and 29%, respectively, compared with no lidocaine administration,” Elizabeth A. Mittendorf, MD, PhD; and Tessa Higgins, BA, of the Dana-Farber Cancer Institute, wrote in an editorial that accompanied the study.2 “These data add to the body of evidence supporting the perioperative use of local anesthetics for multiple reasons...not just this potential oncologic benefit but for providing pain relief, as well as decreasing intraoperative and postoperative opioid use, thereby reducing postoperative nausea and vomiting and facilitating enhanced recovery after surgery.”
The open-label study randomly assigned patients from 11 centers in India 1:1 to receive 0.5% lidocaine not exceeding 4.5 mg/kg of body weight around the 6 tumor surfaces of the patient’s primary tumor after general anesthesia or no lidocaine.1 Patients in both arms subsequently underwent either breast conserving surgery or modified radical mastectomy 7 to 10 minutes after they received local anesthesia. Patients in the surgery-only arm were given the same general anesthetic treatment as the lidocaine arm without local anesthetic being infiltrated around the primary tumor.1
Eligible patients were women with N0 or N1 lymph node status, no evidence of distant metastasis, and an ECOG performance status of 0. Those who had undergone prior excision or incisional biopsy of the primary tumor, neoadjuvant chemotherapy, or hormone therapy were not included in the study. Once enrolled, patients were stratified by cancer center, tumor size (≤ 2 cm vs > 2-5 cm vs > 5 cm), and menopausal status (premenopausal plus perimenopausal vs postmenopausal).
After surgery, standard adjuvant treatment was planned for all patients. Six cycles of an anthracycline-based chemotherapy regimen and 4 cycles of an anthracycline regimen followed by 12 weeks of a taxane regimen were given to patients with node-negative and node-positive disease, respectively. Those with HER2-positive disease were scheduled to receive 12 weeks or 1 year of adjuvant trastuzumab (Herceptin), if the agent was accessible. Standard postoperative radiotherapy was given to all of the patients who underwent breast conserving surgery, as well as those who received modified radical mastectomy who had node-positive disease and/or a tumor size of at least 5 cm. Patients with hormone receptor–positive disease were scheduled to receive 5 years of tamoxifen, or an aromatase inhibitor, depending on if they were premenopausal or postmenopausal, respectively.
The primary end point was DFS. OS was the secondary end point.
Baseline patient characteristics were well-balanced between the lidocaine and surgery-only arms. The median age was 51 years (range, 22-79) vs 51 years (range, 24-84), respectively. Most patients in both arms were postmenopausal (60.7% vs 59.7%), had a clinical tumor size between 2.1 cm and 5 cm (75.3% vs 75%), had grade III disease (74.2% vs 73.1%), and were HER2-negative (77.9% vs 76.8%). A majority of patients in both arms underwent breast conservation, 60.3% vs 63.0%, respectively. Among patients with HER2-positive tumors, 35.1% and 34.2% received adjuvant trastuzumab, respectively.
Additional findings from the study showed that, in terms of DFS, the effect of adding lidocaine did not significantly differ between patients who underwent mastectomy (HR, 0.73; 95% CI, 0.50-1.04) compared with breast conserving surgery (HR, 0.703; 95% CI, 0.496-0.996). The DFS benefit with the addition of lidocaine was also similar in HER2-positive patients who received HER2-targeted therapy (HR, 0.69; 95% CI, 0.25-1.94) vs those who did not (HR, 0.57; 95% CI, 0.30-1.06). The subgroup analysis revealed that the DFS benefit with the addition of lidocaine was reported in all subgroups (HR, 0.69; 95% CI, 0.53-0.88; P = .004).1
Regarding OS, a Cox proportional hazards model that considered age (≤ 50 vs > 50 years), tumor size (≤ 2 cm vs > 2 cm), hormone receptor status (positive vs negative), lymph nodes (negative vs positive), and grade showed that the addition of lidocaine resulted in a significant benefit (adjusted HR, 0.64; 95% CI, 0.47-0.86; P = .003). The OS benefit with lidocaine was also maintained across all subgroups.
In terms of safety, the injection of lidocaine led to no related adverse effects.
“It seems reasonable to introduce this intervention as an easy, cost-effective intervention that may reduce the rates of recurrence and death in women with early-stage breast cancer,” Mittendorf and Higgins concluded.2 “Additional investigation will be required to elucidate the mechanism of this benefit.”