Page 29 - ARNM-3-1

Advances in Radiotherapy
& Nuclear Medicine Chinese Expert Consensus for LACC

whereas the control group included 144 participants. The 3.2. Integration of ICIs with CCRT in LACC treatment
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ORRs in the two groups were 86.3% and 76.3%, respectively, The integration of ICIs with CCRT in LACC treatment
exhibiting a significant difference (P = 0.028). Notably, no represents significant progress over the last decade. ICIs
significant variance (P > 0.05) was noted in the incidence have revolutionized the management of malignant tumors
of grade ≥3 adverse events between the two groups. and reshaped the tumor therapy landscape. The potential of
In this prospective multicenter single-arm Phase ICIs in cervical cancer treatment has remarkably attracted
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II trial, 122 older patients with cervical cancer who the attention of clinicians. By inhibiting T-cell activation
were ineligible for chemotherapy received nituzumab and cytokine production, ICIs reactivate T-cell-mediated
combined with radiotherapy. The partial response rate cytotoxicity and enhance antitumor immune responses by
(PRR), ORR, DCR, and CRR were 45.0% (55/122), impeding immunological checkpoints and ligand binding.
87.7% (107/122), 92.6% (113/122), and 42.6% (52/122), To ensure precise medication dosing, programmed death
ligand-1 (PD-L1) and tumor mutation burden testing are
respectively, with Grade 1 – 2 adverse events being the recommended before initiating ICIs along with CCRT
most common. A meta-analysis involving 393 patients (Table 3).
indicated that the nimotuzumab plus CCRT group
displayed significantly improved CRR (RR = 1.34, 95% Nivolumab, a human monoclonal antibody targeting the
CI 1.08 – 1.65, P = 0.007), ORR (RR = 1.30, 95% CI PD-1 receptor, is the pioneering ICI to receive approval. It
1.16 – 1.44, P < 0.05), and 3-year OS rate (RR = 1.27, has demonstrated efficacy in conditions, such as advanced
95% CI 1.06 – 1.51, P = 0.008) compared with the gastric cancer, recurrent or metastatic squamous head and
radiotherapy group. Notably, the incidence of adverse neck cancer, and locally advanced or metastatic NSCLC.
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events, such as leukopenia, gastrointestinal reactions, During the 2022 ASCO congress, a Phase I clinical trial
investigating nivolumab in combination with CCRT
radiation cystitis, and radiation proctitis, did not exhibit to treat LACC (n = 16) unveiled its findings. The trial
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significant differences between the two groups (P > 0.05). reported an impressive ORR of 93.8% (15/16), CRR of
The evidence supports the safety and clinical benefits of 50% (8/16), and PRR of 43.75% (7/16). The 2-year PFS
nimotuzumab in combination with CCRT, exhibiting rate was 75% (95% CI 56.5 – 99.5%). Among 15 patients
positive short-term efficacy outcomes, such as ORR and evaluable for DLT, three experienced DLT, consisting of
favorable long-term survival (e.g., 3-year OS rate). The two cases of Grade 3 hypotension and one case of Grade 3
recommended nimotuzumab dosage is 200 – 400 mg acute renal injury. No fatalities occurred during the DLT
once weekly for 6 weeks. evaluation. Given that the outcomes of a Phase I trial
• Level of evidence: Medium (nimotuzumab) with a small sample size have yet to be substantiated by
• Grade of recommendation: Strong (nimotuzumab). comprehensive data from a large randomized controlled

Table 3. Clinical studies of immunotherapy drugs in combination with CCRT for LACC

Drug name Researcher Study type No. of RT Follow‑up Efficacy Adverse reactions/events
cases (Mo.)
Atezolizumab Mayadev Phase I study 40 EFRT 20 A Arm ORR 69%, 2-year 3 DLT cases, 7 cases of grade
et al. 29 DFS 79%; B Arm ORR 40%, ≥3 adverse reactions
2-year DFS 59%
Nivolumab Rodrigues Phase I study 16 Not 23.8 ORR 93.8%, CRR 50%, 3 DLT cases
et al. 16 reported PRR 43.75%, 2-year PFS 75%
Camrelizumab Xiao et al. 17 Phase II study 25 IMRT Not CRR 28%, ORR 96.0%, 16% incidence of grade ≥3 adverse
reported DCR 100% reactions
Durvalumab Monk et al. 22 Phase III study 714 EBRT 18.5 1-year PFS 76.0% versus 73.3% Overall rate of grade ≥3 adverse
reactions 28% versus 23%
Pembrolizumab Duska et al. 23 Phase II Study 88 IMRT, 9.2 NA 88% incidence of ≥2-grade TRAEs
EBRT
Pembrolizumab Lorusso Phase III study 1060 EBRT 17.9 2-year PFS 67.8% versus 57.3%, 67.0% versus 60.0% incidence of
et al. 24 2-year OS 87.2% versus 80.8% grade ≥3TRAEs
Abbreviations: CRR: Complete response rate; DCR: Disease control rate; DFS: Disease-free survival; DLT: Dose-limiting toxicity; EBRT: External
beam radiotherapy; EFRT: Extended-field radiotherapy; IMERT: Intensity-modulated external radiotherapy; IMRT: Intensity-modulated radiotherapy;
LACC: Locally advanced cervical cancer; LRF: Locoregional failure; mOS: Median overall survival; ORR: Objective response rate; OS: Overall survival;
PFS: Progression-free survival; SAE: Severe adverse events; TRAE: Treatment-related adverse events.

Volume 3 Issue 1 (2025) 21 doi: 10.36922/arnm.4032