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The Addition of EGFR Inhibitors in Neoadjuvant Therapy for KRAS-Wild Type Locally Advanced Rectal Cancer Patients: A Systematic Review and Meta-Analysis.

ABSTRACT: Background:Patients with locally advanced rectal cancer (LARC) are at higher risk of local and distant recurrence and are thus more vulnerable to metastatic diseases. Neoadjuvant chemoradiotherapy (nCRT) and subsequent curative resection with total mesorectal excision (TME) followed by adjuvant chemotherapy have been recommended by the National Comprehensive Cancer Network (NCCN) guidelines as standard of care for LARC patients. However, the efficacy of the addition of epidermal growth factor receptor (EGFR) inhibitors in kirsten rat sarcoma viral oncogene (KRAS)-wild type LARC patients remains uncertain. Materials:PubMed, Embase, and Web of Science were searched to retrieve records on the application of EGFR inhibitors in a neoadjuvant setting for LARC patients. pCR was used as surrogate endpoint to perform data synthesis in a single-arm setting. Results:Ten cohorts covering 540 subjects were eligible in this systematic review. The pooled pCR rate for EGFR inhibitors was 15% (95% confidence interval (95% CI), 11-20%; I2 = 55.2%); the pooled estimates of Grade 3/4 diarrhea, Grade 3/4 hand-foot syndrome, Grade 3/4 acneiform rash were 17% (95% CI, 4-34%; I2 = 93.3%), 2% (95% CI, 0-5%; I2 = 13.7%), and 15% (95% CI, 9-22%; I2 = 65.4%), respectively. Conclusion:The addition of EGFR inhibitors in the nCRT for KRAS-wild type LARC patients provides comparable efficacy and acceptable safety. However, the results should be interpreted cautiously due to the small amount of relevant data and need further confirmation by more future studies.

SUBMITTER: Zhong X

PROVIDER: S-EPMC7242658 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Addition of EGFR Inhibitors in Neoadjuvant Therapy for KRAS-Wild Type Locally Advanced Rectal Cancer Patients: A Systematic Review and Meta-Analysis.

Zhong Xi X Zhou Yue Y Cui Wanbin W Su Xin X Guo Zhexu Z Hidasa Iko I Li Qincai Q Wang Zhenning Z Song Yongxi Y

Frontiers in pharmacology 20200515

<h4>Background</h4>Patients with locally advanced rectal cancer (LARC) are at higher risk of local and distant recurrence and are thus more vulnerable to metastatic diseases. Neoadjuvant chemoradiotherapy (nCRT) and subsequent curative resection with total mesorectal excision (TME) followed by adjuvant chemotherapy have been recommended by the National Comprehensive Cancer Network (NCCN) guidelines as standard of care for LARC patients. However, the efficacy of the addition of epidermal growth f ...[more]

PMID: 32499700

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Project description:ImportanceTreatment of locally advanced rectal (LARC) cancer involves chemoradiation, surgery, and chemotherapy. The concept of total neoadjuvant therapy (TNT), in which chemoradiation and chemotherapy are administered prior to surgery, has been developed to optimize delivery of effective systemic therapy aimed at micrometastases.ObjectiveTo compare the traditional approach of preoperative chemoradiation (chemoRT) followed by postoperative adjuvant chemotherapy with the more recent TNT approach for LARC.Design, setting, and participantsA retrospective cohort analysis using Memorial Sloan Kettering Cancer Center (MSK) records from 2009 to 2015 was carried out. A total of 811 patients who presented with LARC (T3/4 or node-positive) were identified.ExposuresOf the 811 patients, 320 received chemoRT with planned adjuvant chemotherapy and 308 received TNT (induction fluorouracil- and oxaliplatin-based chemotherapy followed by chemoRT).Main outcomes and measuresTreatment and outcome data for the 2 cohorts were compared. Dosing and completion of prescribed chemotherapy were assessed on the subset of patients who received all therapy at MSK.ResultsOf the 628 patients overall, 373 (59%) were men and 255 (41%) were women, with a mean (SD) age of 56.7 (12.9) years. Of the 308 patients in the TNT cohort, 181 (49%) were men and 127 (49%) were women. Of the 320 patients in the chemoRT with planned adjuvant chemotherapy cohort, 192 (60%) were men and 128 (40%) were women. Patients in the TNT cohort received greater percentages of the planned oxaliplatin and fluorouracil prescribed dose than those in the chemoRT with planned adjuvant chemotherapy cohort. The complete response (CR) rate, including both pathologic CR (pCR) in those who underwent surgery and sustained clinical CR (cCR) for at least 12 months posttreatment in those who did not undergo surgery, was 36% in the TNT cohort compared with 21% in the chemoRT with planned adjuvant chemotherapy cohort.Conclusions and relevanceOur findings provide additional support for the National Comprehensive Cancer Network (NCCN) guidelines that categorize TNT as a viable treatment strategy for rectal cancer. Our data suggest that TNT facilitates delivery of planned systemic therapy. Long-term follow-up will determine if this finding translates into improved survival. In addition, given its high CR rate, TNT may facilitate nonoperative treatment strategies aimed at organ preservation.

Project description:BackgroundTotal neoadjuvant therapy (TNT) is a novel approach for locally advanced rectal cancer (LARC), which attempts to deliver both systemic chemotherapy and neoadjuvant chemoradiotherapy prior to surgery. However, its efficacy and safety remain controversial in randomized controlled trials (RCTs). We conducted this meta-analysis to assess such concerns.Materials and methodsHead-to-head phase II/III RCTs were searched in Embase, PubMed, Web of Science, and the Cochrane Library, as well as other sources. The primary endpoint was pathologic complete response (pCR). Secondary endpoints were disease-free survival (DFS), overall survival (OS), local recurrence-free survival, distant metastasis-free survival, and the R0 resection rate.ResultsEight phase II/III RCTs involving 2,196 patients with LARC were assessed. The primary analysis demonstrated a statistically significant improvement in the pCR rate for TNT treatment (odds ratio, 1.77; 95% confidence interval [CI], 1.28-2.45; p = .0005). TNT treatment also showed improvements in DFS and OS outcomes compared with standard chemoradiotherapy (hazard ratio [HR], 0.83; 95% CI, 0.72-0.96; p = .03 and HR, 0.88; 95% CI, 0.74-1.05; p = .15). In addition, TNT treatment showed significant efficacy in reducing the risk of distant metastasis (HR, 0.81; 95% CI, 0.68-0.95; p = .012).ConclusionThe overall pCR rate may be improved with TNT compared with standard treatment. The TNT strategy may also improve DFS and OS and reduce the risk of distant metastasis.Implications for practiceLocally advanced rectal cancer (LARC) is a relatively common disease, with a poor prognosis because of its high metastatic potential. The role of total neoadjuvant therapy (TNT) has always been controversial. This meta-analysis found that TNT in LARC is associated with a significant improvement in overall pathologic complete response rate, disease-free survival, overall survival, and distant metastasis-free survival compared with standard treatment. TNT is a promising strategy for LARC, especially for patients who have little desire for surgery.

Dataset Information

The Addition of EGFR Inhibitors in Neoadjuvant Therapy for KRAS-Wild Type Locally Advanced Rectal Cancer Patients: A Systematic Review and Meta-Analysis.

Publications

The Addition of EGFR Inhibitors in Neoadjuvant Therapy for KRAS-Wild Type Locally Advanced Rectal Cancer Patients: A Systematic Review and Meta-Analysis.

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