Page 31 - ARNM-3-1

Advances in Radiotherapy
& Nuclear Medicine Chinese Expert Consensus for LACC

respectively (HR 0.61; 95% CI, 0.40 – 0.91, P = 0.04), and patients experienced grade ≥3 ICI-related adverse effects.
5-year PFS rates were 73% and 64% for the IC/CCRT and Dual immunotherapy holds significant promise in clinical
control groups, respectively (HR 0.65; 95% CI, 0.46 – 0.91, research; however, careful evaluation is imperative because
P = 0.013). Grade ≥3 adverse events occurred in 59% and of the increasing adverse events linked with combination
48% of patients in the respective groups. The findings therapies, until strong evidence of therapeutic benefit is
underscored the significant enhancement in PFS and OS established.
among patients with LACC using IC preceding CCRT, • Level of evidence: Low (nivolumab)
demonstrating its feasibility and clinical benefit of this • Expert consensus Level: Weak (nivolumab)
treatment approach. • Level of evidence: Low (ipilimumab)
• Level of evidence: High • Expert consensus: Weak (ipilimumab)
• Expert consensus: Strong. A prospective Phase II study of camrelizumab in the

3.4. ICIs before CCRT in LACC neoadjuvant setting for LACC conducted across multiple
centers employed an open-label, single-arm design. The
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Atezolizumab, a PD-L1 monoclonal antibody, was study enrolled 83 patients, involving 78 subjects who
approved for treating metastatic triple-negative breast underwent evaluation. The induction regimen comprised
cancer, advanced bladder cancer, SCLC, and metastatic one cycle of cisplatin (75 – 80 mg/m , intravenously)
2
NSCLC. 26-28 Findings from a phase I trial combining alongside albumin-bound paclitaxel (260 mg/m ,
2
atezolizumab with CCRT in patients with LACC and intravenously), followed by two cycles of camrelizumab
lymph node metastases (n = 40) were presented in the infusion (200 mg, intravenously, every 3 weeks),
2022 SGO meeting. The study comprised two cohorts: separated by 3-week intervals. Patients exhibiting stable
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(a) administering one cycle of atezolizumab before CCRT, or progressive disease proceeded to CCRT, whereas
followed by two cycles during CCRT, resulted in an ORR those achieving PR or CR underwent radical surgery. In
of 69% and a 2-year DFS rate of 79%. (b) Conversely, June 2023, the study achieved a primary endpoint ORR
when three atezolizumab cycles were administered during of 100%, in which 14 patients achieved CR (17.95%),
CCRT, the ORR decreased to 40% with 2-year DFS rate of 64 with PR (82.05%), and 30 exhibited pathological
59%. Notably, 8% of the participants experienced DLTs, complete response (pCR, 39.47%). In addition,
including thrombocytopenia, immune-related colitis, and 17 (22.37%) patients necessitated postoperative adjuvant
non-immune-associated colitis. Notably, seven patients therapy. During IC, 35 (44.87%) patients experienced
experienced grade ≥3 adverse events. Given the trial’s Phase grade ≥3 adverse events. After the initial publication,
I nature and limited sample size, the clinical outcomes data up to December 2023 revealed an ORR of 98%
were deemed low. Future studies are warranted to further among 83 patients, in which 16 (19%) achieved CR
explore the potential of neoadjuvant immunotherapy. and 67 (79%) demonstrated PR. Lymphopenia (25%),
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• Level of evidence: Low (atezolizumab) neutropenia (12%), and leukopenia (8%) were the most
• Expert consensus level: Weak (atezolizumab). prevalent grade 3 – 4 therapy-related adverse events

The synergistic potential of combining CTLA-4 inhibitors observed during neoadjuvant chemoimmunotherapy.
with PD-1 inhibitors was well-documented. PD-1 and Notably, no severe or treatment-related fatalities were
CTLA-4 collaborate to impede T-cell activation and reduce reported. The study demonstrated that the incorporation
CD28 co-stimulation. Using a combination of PD-1 and of camrelizumab with neoadjuvant chemotherapy for
CTLA-4 inhibitors, the suppressive immunological status of LACC treatment resulted in significant ORR and pCR
effector T cells can be alleviated, diminishing the influences rates, along with manageable toxicity levels, potentially
of regulatory T cells on T effector cells and facilitating the reducing the necessity for postoperative adjuvant therapy.
activation of effector T cells. In a Phase II study involving Nevertheless, the limited sample size underscores the
40 patients with LACC of FIGO 2018 stages IB3-IVA, need for further extensive clinical investigations.
an anti-PD-1 monoclonal antibody was paired with an • Level of evidence: Low (camrelizumab)
anti-CTLA-4 monoclonal antibody. The induction • Expert consensus degree: Weak (camrelizumab).
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regimen included a 2-week treatment plan of nivolumab
(3 mg/kg on days 1 and 15) alongside ipilimumab (1 mg/ 3.5. Maintenance therapy with ICIs after CCRT in
kg on day 1), a CTLA-4 monoclonal antibody, and CCRT. patients with LACC
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Throughout the subsequent 6-month maintenance phase, The NRG-GOG9929 trial represented the pioneering
a cumulative nivolumab dose of 480 mg was administered investigations into the post-CCRT maintenance
>28 days. The CRR was 0% after induction with ICIs, 62.5% treatment of ipilimumab in patients with LACC with
following CCRT, and 82.5% after the study. Notably, three lymph node metastases. The trial aimed to achieve the

Volume 3 Issue 1 (2025) 23 doi: 10.36922/arnm.4032