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. |