ESTRO 2023 - Abstract Book

S1279

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ESTRO 2023

PO-1575 A phase II trial of PRaG regimens rechallenge for PD-1 inhibitor resistance in advanced tumors

M. Xu 1 , C. Zhang 2 , P. Xing 3 , Y. Kong 4 , J. Zhang 5 , L. Zhang 6

1 Institute of Radiotherapy & Oncology, Soochow University; Suzhou Key Laboratory for Radiation Oncology, Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China; 2 Institute of Radiotherapy & Oncology, Soochow University; Suzhou Key Laboratory for Radiation Oncology, Department of Radiotherapy& Oncology,The Second Affiliated Hospital of Soochow University, Suzhou, China, Suzhou, China; 3 Institute of Radiotherapy & Oncology, Soochow University; Suzhou Key Laboratory for Radiation Oncology, Suzhou, China, Department of Radiotherapy& Oncology,The Second Affiliated Hospital of Soochow University, Suzhou, China, Suzhou, China; 4 Institute of Radiotherapy & Oncology, Soochow University; Suzhou Key Laboratory for Radiation Oncology, Suzhou, China, Department of Radiotherapy& Oncology,The Second Affiliated Hospital of Soochow University, Suzhou, China, Suzhou, China; 5 Institute of Radiotherapy & Oncology, Soochow University; Suzhou Key Laboratory for Radiation Oncology, Suzhou, China, Department of Radiotherapy& Oncology,The Second Affiliated Hospital of Soochow University, Suzhou, China, Suzhou, China; 6 Institute of Radiotherapy & Oncology, Soochow University; Suzhou Key Laboratory for Radiation Oncology, Suzhou, China, Department of Radiotherapy& Oncology,The Second Affiliated Hospital of Soochow University, Suzhou, China, Suzhou, China Purpose or Objective Despite more patients of advanced solid tumors obtain tumor regression and long-term survival in the extensive use of PD 1/PD-L1 inhibitor, unfortunately some may develop resistance after an initial response. Finding an effective treatment to rescue with resistance of PD1/PD-L1 inhibitor has been an urgent problem. The PRaG trial as a salvage therapy in advanced solid tumors has obtained satisfactory results. With great surprise we found that patients with PD1/PD-L1 inhibitors resistance are more likely to benefit from the PRaG regimens (PD-1 inhibitor combined with hypofractionated radiotherapy and GM-CSF with or without IL-2). This is the PRaG regimen rechallenge that could represent an attractive option in advanced solid tumors. We retrospectively analyzed the clinical efficacy and safety of PRaG regimen rechallenge to treat immunotherapyrefractory advanced solid tumors. Materials and Methods A total of 13 patients who showed initial resistance to PD-1/PD-L1 inhibitor were retrospectively collected from PRaG serial trails. In a PRaG cycle, SBRT or HFRT(3 × 8Gy or 3 × 5Gy) was delivered for one metastatic site, GM-CSF 200 µ g was subcutaneously injected daily for 2 weeks after radiotherapy(the PRaG 2.0 regimen, GM-CSF 200 µ g SC d1-7, sequentially IL-2 2million IU d8-14.), and PD-1 inhibitor was dosing within one week after completion of radiotherapy. Pooled analysis of response rate (ORR), median progression-free survival (mPFS), and treatment-related adverse events were calculated. The PRaG trial was registered in chictr.org.cn (No. ChiCTR1900020175) and the PRaG 2.0 trial was registered at www.clinicaltrials.gov(No.NCT04892498). Results By September 2022, 13 patients with PD-1 inhibitor resistance were examined. All patients completed at least one efficacy evaluation, involving in lung cancer, renal cancer, liver cancer, colon cancer and sarcoma. The ORR was 15.4%, and the disease control rate (DCR) was 69.2%. The mPFS was 5.2months （ 95%CI ， 1.2 to 9.3 months. One lung cancer achieved complete remission, with PFS over 24 months. Treatment-related adverse events of any grade occurred in 11 of 13(84.6%) patients. While there was no grade 3 or higher adverse events. Conclusion Our preliminary results suggested that PRaG regimens rechallenge was an active and feasible strategy in PD-1/PD-L1 inhibitors resistance. The therapy was well tolerated with acceptable toxicity. A prospective study is in the plan to clarify the role of rechallenge after PD-1/PD-L1 inhibitor resistance. 1 Azienda USL-IRCCS di Reggio Emilia, Radiation Oncology Unit, Reggio Emilia, Italy; 2 University of Modena and Reggio Emilia, Radiation Oncology Unit, Modena, Italy; 3 Azienda USL-IRCCS di Reggio Emilia, Medical Physic Unit, Reggio Emilia, Italy Purpose or Objective Lattice Radiation Therapy (LRT) is a new technique based on an inhomogeneous target irradiation where high doses (vertices) and low doses (periphery) alternate as peaks and valleys, with a periphery-vertices dose escalation of at least 250% of the periphery prescribed dose. LRT allows administering ablative doses to large lesions improving tumor probability response, without an increased toxicity. Thus, LRT may represent a key strategy in the management of large neoplastic lesions (diameter > 5 cm) when surgery is excluded, systemic therapies have poor efficacy, standard radiotherapy achieves limited response, and Stereotactic Body Radiation Therapy is hardly feasible. The aim of our study is to provide further data on LRT safety and efficacy by retrospectively analysing a cohort of patients. Materials and Methods From October 2021, 8 palliative patients with 6 primary bulky unresectable cancers – namely, 2 NSCLC, 1 ovarian carcinoma, 1 melanoma, 1 sarcoma, 1 renal carcinoma - and 2 metastases from an ovarian carcinoma and a melanoma were treated with exclusive LTR. The prescription dose was 20-30 Gy to the entire lesion volume with a simultaneous dose escalation up to 55-66.7 Gy on the vertices, delivered in five daily fractions over one week. We used an in-house software script, developed in MATLAB, to generate the maximum number of vertices inside the target respecting the following dimensions. PO-1576 A retrospective analysis on patients treated with Lattice Radiation Therapy: toxicity and response F. Iori 1,2 , S. Cozzi 1 , P. Ciammella 1 , A. Botti 3 , V. Trojani 3 , L. Giaccherini 1 , M. Iori 3 , C. Iotti 1