Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer

Lin, Zhenyu; Cai, Ming; Zhang, Peng; Li, Gang; Liu, Tao; Li, Xin; Cai, Kailin; Nie, Xiu; Wang, Jing; Liu, Junli; Liu, Hongli; Zhang, Weikang; Gao, Jingbo; Wu, Chen; Wang, Linfang; Fan, Jun; Zhang, Lan; Wang, Zheng; Hou, Zhiguo; Ma, Chi; Yang, Kunyu; Wu, Gang; Tao, Kaixiong; Zhang, Tao

doi:10.1136/jitc-2021-003554

Cited by 77 publications

(85 citation statements)

References 37 publications

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“…In fact, iRT has been a great success to treat patients with cancers including NSCLC, melanoma, and some solid tumors. 365 – 371 Compared with monotherapy, iRT shows significant perspectives to the local control of lesion sites and abscopal effect. Here we systematically summarize the clinical trials of iRT in recent years and explore the potential value in clinical application.…”

Section: Clinical Practicementioning

confidence: 99%

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Zhang

Liu

Chen

et al. 2022

Sig Transduct Target Ther

183

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Radiotherapy (RT) is delivered for purposes of local control, but can also exert systemic effect on remote and non-irradiated tumor deposits, which is called abscopal effect. The view of RT as a simple local treatment has dramatically changed in recent years, and it is now widely accepted that RT can provoke a systemic immune response which gives a strong rationale for the combination of RT and immunotherapy (iRT). Nevertheless, several points remain to be addressed such as the interaction of RT and immune system, the identification of the best schedules for combination with immunotherapy (IO), the expansion of abscopal effect and the mechanism to amplify iRT. To answer these crucial questions, we roundly summarize underlying rationale showing the whole immune landscape in RT and clinical trials to attempt to identify the best schedules of iRT. In consideration of the rarity of abscopal effect, we propose that the occurrence of abscopal effect induced by radiation can be promoted to 100% in view of molecular and genetic level. Furthermore, the “radscopal effect” which refers to using low-dose radiation to reprogram the tumor microenvironment may amplify the occurrence of abscopal effect and overcome the resistance of iRT. Taken together, RT could be regarded as a trigger of systemic antitumor immune response, and with the help of IO can be used as a radical and systemic treatment and be added into current standard regimen of patients with metastatic cancer.

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Section: Clinical Practicementioning

confidence: 99%

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Zhang

Liu

Chen

et al. 2022

Sig Transduct Target Ther

183

141

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“…This significant change in treatment mode may be influenced by a phase II clinical study of SCRT sequential 2-cycle CapOX plus immunotherapy conducted by our center. The pCR rate was 48% in this prospective study [ 8 ]. This kind of neoadjuvant therapy mode based on SCRT shows an amazing curative effect.…”

Section: Discussionmentioning

confidence: 92%

“…Neoadjuvant chemoradiotherapy, as a key preoperative treatment for TME of mid and low LARC, not only helps to reduce the local recurrence rate, achieve tumor downstaging, and improve the R0 resection rate of surgery, but also enables some patients to achieve pathological complete response (pCR). In recent years, domestic and foreign researchers have conducted a large number of clinical studies on preoperative nCRT modalities, and the study data showed that about 8–48% of patients with mid and low LARC could achieve pCR after nCRT [ 4 – 8 ]. It can be seen that there are large individual differences in response to the efficacy of different neoadjuvant treatment modalities.…”

Section: Introductionmentioning

confidence: 99%

Current status of neoadjuvant therapy for locally advanced rectal cancer in Wuhan Union Hospital Cancer Center

et al. 2022

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Background To analyze and explore the evolution and short-term efficacy of neoadjuvant therapy for patients with mid and low LARC in Wuhan Union Hospital Cancer Center. Methods Patients diagnosed with rectal cancer from January 2015 to December 2021 were collected. The treatment patterns, short-term efficacy and treatment-related adverse events (AEs) of mid and low LARC patients who received neoadjuvant therapy were analyzed. The Chi-square test was used to compare the differences between groups. Results A total of 980 patients with mid and low LARC were enrolled, over time, the proportion of patients receiving neoadjuvant therapy gradually increased, and the treatment mode of direct surgery after diagnosis was gradually watered down. More than 80% of the patients implemented radiotherapy-based neoadjuvant therapy, and the proportion of patients receiving SCRT sequential systemic therapy gradually exceeded that of LCRT combined chemotherapy after 2020. Of all patients who completed radiotherapy and underwent surgery, 170 patients received long-course chemoradiotherapy (LCRT) combined with chemotherapy (Group C) and 98 patients received short-course radiotherapy (SCRT) combined with systemic therapy (chemotherapy with or without immunotherapy) (Group D). The pathological complete response (pCR) rate in Group D was significantly higher than that in Group C (38.8% vs. 19.4%, P = 0.001). The pCR rate in the SCRT plus immunotherapy group was better than that in the group without immunotherapy (49.2% vs. 21.6%, P = 0.007). 82.3% of the patients receiving immunotherapy were treated with SCRT sequential 2-cycle CapOX plus Camrelizumab treatment, and the pCR was as high as 52.9%. Immunotherapy did not increase the incidence of Grade 3–4 AEs. Conclusions Neoadjuvant therapy based on radiotherapy is becoming used in patients with mid and low LARC. SCRT sequential systemic therapy is increasingly widely used in LARC patients in our center. Compared with the traditional LCRT or SCRT sequential chemotherapy, SCRT sequential chemotherapy plus immunotherapy has a remarkable pCR rate and manageable toxicity. Looking forward this new treatment mode will bring lasting survival benefits to patients.

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“…No grade 3–4 immune-related adverse effects were observed. Another Chinese study that used SCRT followed by 2 cycles of XELOX and camrelizumab published their findings recently [ 26 ]. Among the 27 patients (26 MSS and 1 MSI-H), the pCR rate was as high as 48% (46% in the MSS group and 100% in the MSI-H group).…”

Section: Discussionmentioning

confidence: 99%

Short-course radiotherapy combined with CAPOX and Toripalimab for the total neoadjuvant therapy of locally advanced rectal cancer: a randomized, prospective, multicentre, double-arm, phase II trial (TORCH)

et al. 2022

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Background For patients with locally advanced (T3-4/N +) rectal cancer (LARC), the standard treatment is neoadjuvant chemoradiotherapy combined with total mesorectal resection, which greatly decreases local recurrence but does not improve overall survival. For patients who achieve a complete clinical response (cCR) after nCRT, a “Watch & Wait” (W&W) approach can be received to improve quality of life. Currently, total neoadjuvant therapy (TNT) has been demonstrated to increase the complete response rate and achieve early control of distant metastasis. Recent studies have shown promising synergistic effects of the combination of immunotherapy (PD-1/PD-L1 antibodies) and radiotherapy. Thus, for LARC patients, the combination of immunotherapy and TNT is likely to further improve the rate of complete response and prognosis. The disparities between induction therapy and consolidation therapy need to be investigated. Methods TORCH is a randomized, prospective, multicentre, double-arm, phase II trial of short-course radiotherapy (SCRT) combined with chemotherapy and immunotherapy in LARC. 130 LARC patients will be treated with the TNT approach and assigned to the consolidation arm and induction arm. The consolidation arm will receive SCRT, followed by 6 cycles of capecitabine plus oxaliplatin (CAPOX) and Toripalimab. The induction arm will first receive 2 cycles of CAPOX and Toripalimab, then receive SCRT, followed by 4 cycles of CAPOX and Toripalimab. Both groups will receive curative surgery or the W&W strategy. The primary endpoint is the complete response rate (rate of pCR plus cCR). The secondary endpoints include the grade 3–4 acute adverse effects rate, 3-year disease-free survival (DFS) rate, 3-year local recurrence-free survival (LRFS) rate, 3-year OS rate, rate of surgical complications and quality of life (QoL) scores. The “pick the winner” method is used to investigate the better treatment regimen. The trial was opened on 13th April 2021, and the first patient was recruited on 6th May 2021. Discussion TORCH will investigate whether SCRT combined with chemotherapy and Toripalimab can achieve better complete response rates, good tolerance and prognosis in LARC patients. This is the first clinical trial to compare the efficacy of induced immunotherapy and consolidative immunotherapy based on the TNT strategy. Trial registration Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT04518280, August 15, 2020.

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Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer

Cited by 77 publications

References 37 publications

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Current status of neoadjuvant therapy for locally advanced rectal cancer in Wuhan Union Hospital Cancer Center

Short-course radiotherapy combined with CAPOX and Toripalimab for the total neoadjuvant therapy of locally advanced rectal cancer: a randomized, prospective, multicentre, double-arm, phase II trial (TORCH)

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