Adjuvant chemotherapy for patients with locally advanced cervical carcinoma receiving definitive chemoradiation; utilization and outcomes before the OUTBACK trial (361)

Abstract

Objectives: To investigate the utilization and outcomes of adjuvant multi-agent chemotherapy for patients with locally advanced cervical carcinoma receiving definitive chemoradiation. Methods: The National Cancer Database was accessed, and patients with no history of another tumor diagnosed between 2004 and 2015 with FIGO 2009 stage IB2-IVA squamous, adenosquamous, or adenocarcinoma of the cervix who received definitive chemoradiation (defined as external beam radiation therapy to the pelvis/cervix of at least 45 Gy with or without the use of vaginal brachytherapy), as well as chemotherapy within one week from radiotherapy initiation, did not undergo hysterectomy and had at least one month of follow-up were identified. Patients who received radio-sensitizing single-agent chemotherapy and those who received adjuvant multi-agent chemotherapy were selected for further analysis. Overall survival was evaluated following generation of Kaplan-Meier curves and compared with the log-rank test while a Cox model was constructed to control for a priori selected confounders. Results: A total of 9895 patients were identified; 8892 (89.9%) received single-agent chemotherapy while 1003 (10.1%) received multi-agent adjuvant chemotherapy. There were no differences between the two groups in terms of patient age, race, insurance status, presence of comorbid conditions, type of treatment facility, and tumor histology. Patients who received adjuvant multi-agent chemotherapy were less likely to receive vaginal brachytherapy (60.9% vs 68.4%, p<0.001). The rate of adjuvant multi-agent chemotherapy was higher among patients with stage IVA (18.1%) and stage III (11.9%) disease compared to those with stage II (8.4%) and stage IB2 (7.2%) disease (p<0.001). Use of adjuvant multi-agent chemotherapy decreased from 12.7% among patients diagnosed between 2004-2007 to 10.5% and 8.6% among those diagnosed between 2008-2011 and 2012-2015, respectively. Patients who received adjuvant multi-agent chemotherapy had worse OS compared to those who did not (median OS: 72.05 vs 103.33 months, p<0.001). However, after controlling for patient age, race, presence of comorbid conditions, insurance status, receipt of vaginal brachytherapy, and disease stage, administration of adjuvant multi-agent chemotherapy was not associated with a survival benefit (HR: 1.09, 95% CI: 0.98-1.20). Following stratification by disease stage, no survival benefit of adjuvant multiagent chemotherapy was found for patients with stage IB (p=0.002; 5-yr OS: 59.2% vs 74.9% favoring single-agent chemotherapy), stage II (p=0.41; 5-yr OS 63.8% vs 67.6%), stage III (p=0.52; 5-yr OS: 48% vs 47.8%) or IVA disease (p=0.27; 5-yr OS: 29.5% vs 34.3%). Conclusions: Contrary to major guidelines, approximately one in ten patients with locally advanced cervical carcinoma undergoing definitive chemoradiation received adjuvant multi-agent chemotherapy with no survival benefit. Objectives: To investigate the utilization and outcomes of adjuvant multi-agent chemotherapy for patients with locally advanced cervical carcinoma receiving definitive chemoradiation. Methods: The National Cancer Database was accessed, and patients with no history of another tumor diagnosed between 2004 and 2015 with FIGO 2009 stage IB2-IVA squamous, adenosquamous, or adenocarcinoma of the cervix who received definitive chemoradiation (defined as external beam radiation therapy to the pelvis/cervix of at least 45 Gy with or without the use of vaginal brachytherapy), as well as chemotherapy within one week from radiotherapy initiation, did not undergo hysterectomy and had at least one month of follow-up were identified. Patients who received radio-sensitizing single-agent chemotherapy and those who received adjuvant multi-agent chemotherapy were selected for further analysis. Overall survival was evaluated following generation of Kaplan-Meier curves and compared with the log-rank test while a Cox model was constructed to control for a priori selected confounders. Results: A total of 9895 patients were identified; 8892 (89.9%) received single-agent chemotherapy while 1003 (10.1%) received multi-agent adjuvant chemotherapy. There were no differences between the two groups in terms of patient age, race, insurance status, presence of comorbid conditions, type of treatment facility, and tumor histology. Patients who received adjuvant multi-agent chemotherapy were less likely to receive vaginal brachytherapy (60.9% vs 68.4%, p<0.001). The rate of adjuvant multi-agent chemotherapy was higher among patients with stage IVA (18.1%) and stage III (11.9%) disease compared to those with stage II (8.4%) and stage IB2 (7.2%) disease (p<0.001). Use of adjuvant multi-agent chemotherapy decreased from 12.7% among patients diagnosed between 2004-2007 to 10.5% and 8.6% among those diagnosed between 2008-2011 and 2012-2015, respectively. Patients who received adjuvant multi-agent chemotherapy had worse OS compared to those who did not (median OS: 72.05 vs 103.33 months, p<0.001). However, after controlling for patient age, race, presence of comorbid conditions, insurance status, receipt of vaginal brachytherapy, and disease stage, administration of adjuvant multi-agent chemotherapy was not associated with a survival benefit (HR: 1.09, 95% CI: 0.98-1.20). Following stratification by disease stage, no survival benefit of adjuvant multiagent chemotherapy was found for patients with stage IB (p=0.002; 5-yr OS: 59.2% vs 74.9% favoring single-agent chemotherapy), stage II (p=0.41; 5-yr OS 63.8% vs 67.6%), stage III (p=0.52; 5-yr OS: 48% vs 47.8%) or IVA disease (p=0.27; 5-yr OS: 29.5% vs 34.3%). Conclusions: Contrary to major guidelines, approximately one in ten patients with locally advanced cervical carcinoma undergoing definitive chemoradiation received adjuvant multi-agent chemotherapy with no survival benefit.