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Table 2 Summary of published clinical trials combining immune checkpoint inhibitors with chemotherapy/radiotherapy in cancer treatment

From: Ferroptosis, necroptosis, and pyroptosis in anticancer immunity

Treatment modality Trial number Cancer type Potential nonapoptotic cell death pathway Main conclusion
Pembrolizumab (anti-PD-L1) + pemetrexed and a platinum-based drug (chemotherapy) NCT02578680 Non-small cell lung cancer Ferroptosis/pyroptosis/necroptosis In patients with previously untreated metastatic non-squamous NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum-based drug resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.
Atezolizumab (anti-PD-L1) + bevacizumab plus carboplatin plus paclitaxel (chemotherapy) NCT02366143 Non-small cell lung cancer Ferroptosis/pyroptosis/necroptosis Improved survival was noted among patients treated with immunotherapy + chemotherapy compared with those only given chemotherapy.
Atezolizumab (anti-PD-L1) + platinum-based chemotherapy NCT02367781 Non-squamous non-small cell lung cancer Ferroptosis/pyroptosis/necroptosis Improved survival was noted among patients treated with immunotherapy + chemotherapy compared with those only given chemotherapy.
Atezolizumab (anti-PD-L1) + platinum (chemotherapy) NCT02807636 Locally advanced or metastatic urothelial carcinoma Ferroptosis/pyroptosis/necroptosis The use of atezolizumab plus platinum-based chemotherapy as a potential first-line treatment option for metastatic urothelial carcinoma.
Pembrolizumab (anti-PD-L1) + stereotactic body radiotherapy NCT02492568 Advanced non-small cell lung cancer Ferroptosis/necroptosis The overall response rate is larger in the group with radiotherapy + immunotherapy; however, the positive results were largely influenced by the PD-L1-negative subgroup.
Pembrolizumab (anti-PD-L1) + docetaxel (chemotherapy) NCT02574598 Non-small cell lung cancer Necroptosis The combination of pembrolizumab plus docetaxel was well tolerated and substantially improved the ORR and PFS in patients with advanced NSCLC who had previous progression after platinum-based chemotherapy.
Ipilimumab (anti-CTLA4) + stereotactic ablative radiation therapy NCT02239900 Metastatic lesions in the liver or lung Ferroptosis/necroptosis This phase II trial of ipilimumab with stereotactic radiotherapy describes satisfactory outcomes and low toxicities, lending support to the further investigation of combined-modality therapy for metastatic cancers.