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Ipilimumab ‘Feasible’ Option For Locally Advanced Cervical Cancer

Research suggests ipilimumab has potential to play a role in the management of lymph node-positive cervical cancer
02 Dec 2019
Basic Scientific Principles;  Cervical Cancer;  Clinical Research;  Immunotherapy;  Therapy
By Lynda Williams, Senior medwireNews Reporter

Author: By Lynda Williams, Senior medwireNews Reporter

medwireNews: Preliminary study findings indicate that ipilimumab could be given after chemoradiotherapy (CRT) with curative intent to patients with lymph node (LN)-positive cervical cancer. 

“[T]his phase 1 study is the first to show tolerability with a signal of efficacy of an immune checkpoint inhibitor, anti–CTLA-4, as a part of the definitive treatment of locally advanced cervical cancer”, say Jyoti Mayadev, from the University of California, San Diego in La Jolla, USA, and co-investigators. 

“Our data suggest that sequential ipilimumab treatment after standard CRT was feasible with few grade 3 adverse effects, all of which were self-limiting”, they write in JAMA Oncology. 

Overall, 34 women with stage IB2–IVA disease with positive pelvic and/or para-aortic LNs were followed up for a median 14.8 months after completing a 6-week course of cisplatin 40 mg/m2 given concurrently with extended-field radiotherapy to the LNs followed by intracavitary brachytherapy. 

Within 6 weeks of completing CRT, women without evidence of progression began ipilimumab at a starting dose of 3 mg/kg or 10 mg/kg every 3 weeks for four cycles. 

Overall, 32 patients were included in the intention-to-treat analysis. Twenty-one women received at least two cycles of ipilimumab, 86% of whom completed four cycles of the agent. 

None of the three patients given ipilimumab 3 mg/kg or five patients given the 10 mg/kg dose in the dose-finding portion of the study experienced a dose limiting toxicity, and the maximum tolerated dose was set at 10 mg/kg. 

However, two of the 13 patients in the feasibility phase of the study experienced self-limiting grade 3 lipase elevation or dermatitis, respectively, and one patient delayed cycle 4 for self-limiting neutrophilia. There were no grade 4 or 5 adverse events and most acute toxicities were grade 1 or 2 diarrhoea, dermatitis and endocrinopathies, the researchers note.  

The ipilimumab-treated patients all had positive pelvic LNs and 29% had positive para-aortic LNs. 

At 12 months, 81% were free from disease progression and 90% were alive, which the researchers describe as “promising” compared with historical reported rates of 63% and 80%, respectively, in a similar patient population. 

Moreover, patients had an increase in PD-1-expressing T cells after CRT and that this effect was sustained during ipilimumab therapy, which the researchers suggest may indicate “immune activation with radiotherapy”, although they were unable to assess tumour expression of PD-1 or PD-L1. 

Nevertheless, Jyoti Mayadev et al hypothesize that “the PD-1 expression seen after CRT and ipilimumab therapy could contribute to immune exhaustion or treatment resistance, which could be a potential target for novel therapies in node-positive cervical cancer.” 

 

Reference  

Mayadev JS, Enserro D, Lin YG, et al. Sequential ipilimumab after chemoradiotherapy in curative-intent treatment of patients with node-positive cervical cancer. JAMA Oncol; Advance online publication 27 November 2019. doi:10.1001/jamaoncol.2019.3857

Last update: 02 Dec 2019

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

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