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

Abstract

Findings on the efficacy of adjuvant chemotherapy (ACT) of locally advanced cervical cancer (LACC) after the concurrent chemoradiation (CCRT) therapy were inconsistent, and the OUTBACK trial was expected to shed some light regarding the topic. Its results on ACT in LACC were negative, with the conclusion of not to use it. The objective of this review was to present the inconsistencies of previous studies, along with the OUTBACK trial in more detail, and to rethink whether its results provide an unambiguous and definite answer to the optimal position of ACT in the treatment of LACC. To critically appraise the OUTBACK trial and understand the consequences of its results, we used only randomized controlled studies (RCTs) on ACT in LACC that have been included in high-quality systematic reviews and meta-analyses. We calculated the pooled prediction intervals using a random effects meta-analysis of all published randomized studies including the OUTBACK trial. After combining the OUTBACK trial with the results of four previous randomized trials, the pooled hazard ratio for overall survival benefit of CCRT + ACT was 0.95 (95% CI 0.75; 1.20). The pooled hazard ratio of the four previous trials was 1.00 (95% CI 0.69; 1.44). The OUTBACK trial improved the precision of the pooled estimate, but the clinical heterogeneity and the consequent prediction intervals are still very wide, and with 95% reliability, we can expect that if the new study, using a similar approach to the ACT, on a randomly selected patient population from the presented five trials is conducted, its hazard ratio for overall survival after ACT would be between 0.47 and 1.93. In conclusion, there is an absolute need for further research in order to optimally define the position of ACT in the treatment of LACC.

Efficacy of lymph node dissection on stage IIICr of cervical cancer before CCRT: study protocol for a phase III, randomized controlled clinical trial (CQGOG0103)

“…The ACT should be performed for the patients with residual disease confirmed by cervical biopsy and/or image-positive lymph nodes (short diameter ≥15 mm) in our trial. Despite the OUTBACK trial shown negative result on ACT, the efficacy of ACT of LACC after CCRT were inconsistent [ 28 29 ]. The experts of our trial consider the residual disease after CCRT as the possible helpful factor in identifying subtype that could derive benefit from ACT.…”

Definitive Chemoradiation for Locally Advanced Cervical Cancer: A Review of the Literature

“…Въпреки ползата за преживяемостта, отчетена в някои от тези проучвания, АХТ все още не се смята за стандарт на лечение (13). Резултатите от текущото проучване OUTBACK (5) (седмична доза Цисплатин по време на ЛХЛ, последвани от четири цикъла Паклитаксел плюс Карбоплатин като адювантна терапия) могат да предоставят допълнителни доказателства за ролята на ХТ в адювантен аспект (5). Последните публикувани резултати от проучването показват, че АХТ след едновременно ЛХЛ не подобрява преживяемост в сравнение с едновременното ЛХЛ, и в групата на АХТ са наблюдавани значително повече нежелани събития (28).…”

Immune checkpoint blockade for locally advanced or recurrent/metastatic cervical cancer: An update on clinical data

“…A phase III clinical study (OUTBACK Trial) showed that four cycles of adjuvant chemotherapy with Paclitaxel plus Carboplatin following standard CCRT did not prolong patient survival ( 13 ). Most current studies do not recommend adjuvant chemotherapy for LACC patients ( 14 ). Targeted anti-angiogenesis inhibitor therapy with Endostar in combination with CCRT increased the distance metastasis-free survival (DMFS) but did not improve progression-free survival (PFS) ( 15 ).…”