Page 30 - ARNM-3-1

Advances in Radiotherapy
& Nuclear Medicine Chinese Expert Consensus for LACC

clinical study, nivolumab is not recommended for treating microsatellite instability or deficient mismatch repair genes.
patients with LACC. In 2020, a Phase II randomized trial was performed to
• Level of evidence: Low (nivolumab) evaluate the safety of pembrolizumab combined with CCRT
• Grade of recommendation: Weak (nivolumab). for treating LACC. Group A received pembrolizumab post-
Cedelizumab, a humanized anti-PD-1 monoclonal CCRT, whereas Group B received pembrolizumab plus
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antibody initially developed by a Chinese company, can CCRT. Among 88 patients, 52 completed the treatment
regimen as per the findings. Adverse events of grade ≥2
be employed in the treatment of Hodgkin’s lymphoma, linked to therapy were noted in 88% of cases. No significant
hepatocellular carcinoma (HCC), esophageal cancer, and difference was found in the occurrence of grade ≥1 severe
advanced lung cancer. A Phase II study investigating the
combination of cedelizumab with CCRT in patients with diarrhea between the two groups (63% in group A vs.
LACC was presented at the 2022 ESMO congress. The 68% in group B). Notably, two patients experienced three
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study outcomes were CRR, ORR, and DCR of 28% (7/25), instances of dose-limiting adverse events.
96.0% (24/25), and 100% (25/25), respectively. Among The results of the midterm analysis from a Phase
the immune-related adverse events, reactive capillary III randomized controlled clinical trial investigating
hyperplasia was the most prevalent (92.0%), followed by pembrolizumab combined with CCRT for LACC treatment
enterocolitis (80.0%) and anemia (56.0%), with severity were unveiled at the 2023 ESMO congress. The study
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Grades 1 – 2. Severe adverse events affected 16.0% of encompassed 1060 patients with high-risk LACC, who
participants (4 out of 25). Further studies are needed to were diagnosed using the 2014 FIGO as having clinical
collect long-term survival data. stages IB2–IIB with lymph node metastases or stages III–
• Level of evidence: Low (cedelizumab) IV irrespective of lymph node involvement, where PD-1
• Grade of recommendation: Weak (cedelizumab). testing was not obligatory. The average follow-up time was
17.9 months. The trial group exhibited a 2-year PFS rate of
Durvalumab, a humanized monoclonal antibody,
targets PD-L1 to inhibit its engagement with PD-1 and 67.8%, whereas the control group showed 57.3% (hazard
ratio [HR] = 0.70 [95% CI, 0.55–0.89; P = 0.0020]). The
CD8, thereby impeding tumor immune evasion and 2-year OS rate was 80.8% (95% CI, 74.8 – 85.5%) and
provoking immune responses. It is also employed as a 87.2% (95% CI, 82.4 – 90.8%) in the trial and control
frontline therapy for SCLC, advanced biliary tract cancer, groups, respectively. Grade ≥3 adverse events occurred
unresectable locally advanced or metastatic bladder cancer, in 67.0% of the trial group compared with 60.0% in the
and advanced HCC. 18-21 A recent Phase III trial assessed control group. The Phase III trial indicated the therapeutic
the efficacy of durvalumab in treating LACC. The primary potential of pembrolizumab for patients with high-risk
endpoint of the CALLA trial, a multicenter double- LACC, illuminating novel insights for immunotherapy in
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blind study, was PFS in 714 patients with high-risk LACC conjunction with CCRT. However, comprehensive long-
who were randomized to receive durvalumab or placebo term follow-up data are eagerly anticipated. Encouraging
alongside CCRT. The 2023 follow-up data from the CALLA patient participation in clinical trials is crucial, and
trial revealed that neither group achieved a median PFS. vigilance toward the adverse effects of immunotherapy
The 12-month PFS rate for the durvalumab group was in combination with CCRT is vital. The recommended
76.0% (95% CI, 71.3 – 80.0), whereas the placebo group administration involves 200 mg of pembrolizumab
reached 73.3% (95% CI, 68.4 – 77.5). Notably, in both alongside CCRT every 3 weeks for five cycles, followed by
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groups anemia (20% [76/385] with durvalumab and 15% 400 mg every 6 weeks for a total of 15 cycles.
[56/384] with placebo) and leukopenia (10% [39/385] with • Level of evidence: high (pembrolizumab)
durvalumab vs. 13% [49/384] with placebo) were the most • Grade of recommendation: Strong (pembrolizumab)
prevalent Grade 3 – 4 adverse events. Furthermore, serious
adverse events were reported in 23% (89/385) of placebo 3.3. Induction chemotherapy (IC) before CCRT in
recipients and 28% (106/384) of durvalumab recipients. LACC
The integration of immunotherapy with CCRT in treating A randomized, controlled Phase III trial involving
LACC has not been endorsed based on the disappointing 500 patients with LACC was presented at the 2023 ESMO
results of the Phase III study. Congress to assess the safety and efficacy of IC preceding
• Level of evidence: Low (durvalumab) CCRT. The average follow-up time was extended to
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• Grade of recommendation: Strong (durvalumab).
64 months. The study incorporated a CCRT control arm
Pembrolizumab is approved for managing melanoma, and an IC/CCRT arm (comprising 6 weeks of carboplatin
NSCLC, esophageal cancer, head and neck squamous plus paclitaxel at 80 mg/m ). At 5 years, OS rates were
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carcinoma, and metastatic colorectal cancer with high 80% and 72% for the control and IC/CCRT groups,

Volume 3 Issue 1 (2025) 22 doi: 10.36922/arnm.4032