Real-World Efficacy and Safety of Bevacizumab in the First-Line Treatment of Metastatic Cervical Cancer: A Cohort Study in the Total Population of Croatian Patients

Abstract

Background. Although today it is almost preventable, cervical cancer still represents a significant cancer burden, especially in some developing parts of the world. Since the introduction of bevacizumab in the first-line treatment of metastatic disease, improvements of the outcomes were noted. However, results from randomized controlled trials are often hard to recreate in the real-world setting. Objective. To assess the real-world efficacy and safety of bevacizumab as a first-line treatment of advanced cervical cancer. Methods. We conducted a retrospective cohort study on the total population of Croatian patients diagnosed with metastatic cervical cancer from 2016 to 2019 who were treated with bevacizumab in combination with cisplatin and paclitaxel (TCB) in the first line. The comparison group was the consecutive sample of patients treated with chemotherapy alone. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate, incidence of adverse events, and the proportion of treatment discontinuation. Results. We enrolled 67 patients treated with TCB and a control group of 62 patients treated with chemotherapy alone. The TCB cohort had significantly longer unadjusted OS with a median of 27.0 (95% CI 18.5; not calculable) months, compared to 15.5 (10.7; 30.1) months in the chemotherapy-alone cohort. Adjusted OS was not significantly different. PFS was significantly longer for the TCB cohort, with a median of 10.6 (95% CI 8.5; 15.4) months, than for the chemotherapy-alone cohort, with a median of 5.4 (95% CI 3.9; 9.1) months, even after adjustment for baseline covariates (HRadjusted = 0.60; 95% CI 0.39; 0.94; p = 0.027 ; false discovery rate <5%). Conclusions. In a real-world setting, TCB as a first-line treatment of metastatic cervical cancer was associated with longer PFS, better objective disease control rate, and acceptable toxicity profile in comparison to chemotherapy alone. These results may indicate its utility and potential applicability in other parts of the developing world.

Is There a Place for Adjuvant Chemotherapy in the Treatment of Locally Advanced Cervical Cancer?

“… Data are presented in CCRT + ACT arm/in control CCRT only arm if not stated otherwise. Abbreviations: OS, overall survival; HR, hazard ratio; CI, confidence interval; CCRT, concurrent chemoradiation; ACT, adjuvant (consolidation) chemotherapy; RT, radiotherapy; n.a., not available; CIS, cisplatin; GEM, gemcitabine; FU, fluorouracil; PAC, paclitaxel; CAR, carboplatin; A, AUC; MIT, mitomycin C. a Mexico, Argentina, India, Panama, Bosnia and Herzegovina, Peru, Thailand, Pakistan, Australia; b Australia, New Zealand, USA, Saudi Arabia, Canada, China, Singapore; c HR was calculated by Parmar [ 37 ] and Tierney [ 38 ] methods; d Minimization using Pocock and Simon algorithm [ 39 ], balancing disease stage (IIB vs. III-IVA), tumor diameter (<5 cm vs. ≥5 cm), study center (not clear, probably 9 that is one per country), radiation equipment (cobalt-60 vs. linear accelerator), age (<55 vs. ≥55 years); e Stratified for six study centers; f Stratified for tumor stage; g Mixed block with stratification for disease stage (IIV vs. III-IVA) and histopathology (squamous vs. adenocarcinoma or adenosquamous carcinoma); h Stratified for nodal status, participating site, FIGO stage, age, planned extended-field radiotherapy; i Mean instead of median; j Interquartile range instead of range; k Including IIIB and IVA; l Estimated from categories (≤4; 4.1–6; 6.1–8; ≥8.1) weighted by frequencies; m Including squamous cell, poorly differentiated and adeno/squamous carcinoma; n Para-aortic lymph nodes >1 cm were exclusion criteria, but 2.3% in ACT arm and 4.7% in CCRT alone arm had at least one; o Previous chemotherapy was not an exclusion criterion, but all patients had newly diagnosed cervical cancer, so the previous chemotherapy/radiotherapy were allowed only for other cancers; p However, not for cervical cancer; q Rounded down to the last full month. …”

Gastrointestinal/genitourinary perforation and fistula formation with or without bevacizumab in patients with previously irradiated recurrent cervical cancer: a Korean multicenter retrospective study of the Gynecologic Oncology Research Investigators Collaboration (GORILLA) group (GORILLA-1001)

“…However, there is a paucity of data regarding the fistulas or perforations involving the bowel and bladder, especially in patients with previously irradiated recurrent cervical cancer. In addition, although randomized controlled trials show significant results in terms of efficacy and safety, they do not always represent the real-world setting [ 10 ]. The purpose of this study is to evaluate the incidence rate and identify the risk factors for GI and GU fistula/perforation in patients receiving bevacizumab plus conventional chemotherapy (BC) for recurrent cervical cancer after pelvic RT in the Korean population.…”