Table 2.
Selected clinical studies with published results.
| Autophagy-Inhibitor | Combination with | Tumor Entity | Outcome | Clinical Phase | Number of Patients | Reference |
|---|---|---|---|---|---|---|
| HCQ | Gemcitabine, nab-Paclitaxel |
Pancreatic cancer (metastatic or advanced) |
Primary endpoint: 12-month overall survival not improved. Improvement in overall response rate. | II | 112 | [97] |
| HCQ | Gemcitabine, nab-Paclitaxel |
Pancreatic cancer (potentially resectable) |
Primary endpoint: histological response at resection improved. HCQ led to increased autophagy-inhibition and immune activity in the tumor. | II | 64 | [98] |
| HCQ | None | Pancreatic cancer (previously treated and metastatic) | Inconsistent autophagy inhibition. No survival benefits. | II | 20 | [99] |
| HCQ | Gemcitabine | Pancreatic cancer (adenocarcinoma, preoperative) | Patients with >51% reduction of autophagy (surrogate: LC3-II in circulating PMNs) had significant (p < 0.05) improvement in disease-free survival (15.03 vs. 6.9 months) and median overall survival (34.83 vs. 10.83 months). | I/II | 35 | [100] |
| HCQ | Imatinib | Chronic myeloid leukemia (major cytogenetic response with residual disease) | 12 months: ’Success’ rate not improved. Major Molecular Remission (MMR): 80% (Imatinib) compared to 92% (Imatinib/HCQ) (n.s.). 24 months: ’Success’ rate increased 20.8% for Imatinib/HCQ vs. Imatinib (n.s.). | II | 62 | [102] |
| CQ | None | Breast cancer (preoperative) | No effect on cancer cell proliferation (n.s.). | II | 70 | [114] |
| HCQ | Everolimus | Clear-cell renal cell carcinoma (previously treated) | Longer stable disease in some patients, inconsistent autophagy inhibition. | I/II | 38 | [104] |
| CQ | Whole-brain irradiation | Brain metastases | Overall response rate (ORR): CQ 54% vs. Control 55% (n.s.). Progression-free survival: CQ 83.9% (95% CI 69.4–98.4) control 55.1% (95% CI 33.6–77.6). CQ significantly improves PFS: RR 0.31 (95% CI [0.1–0.9]). No difference in response rate or overall survival. | II | 73 | [115] |
| HCQ | Carboplatin, Paclitaxel, Bevacizumab (if criteria met) |
NSCLC (metastatic and untreated) |
Progression-free survival longer than expected. | Ib/II | 40 | [103] |
| HCQ | Radiation therapy; concurrent, adjuvant Temozolomide | Glioblastoma multiforme (newly diagnosed) | No significant improvement in overall survival. Significant but inconsistent autophagy inhibition. | I/II | 92 | [116] |
| HCQ | Temsirolimus | Advanced solid tumors and melanoma | No significant improvements | I | 40 | [105] |
| HCQ | Sirolimus | Lymphangioleiomyomatosis | No improvement of lung function | I | 14 | [117] |
| HCQ | Bortezomib | Multiple Myeloma (relapsed, refractory) |
Very good partial responses (14%), minor response (14%), temporary stable disease (45%) | I | 25 | [118] |
| HCQ | MK-2206 (AKT inhibitor) |
Advanced solid tumors | Stable disease 15%. No significant antineoplastic activity. |
I | 35 | [119] |
| HCQ | Temozolomide | Advanced solid tumors and melanoma | Metastatic melanoma: Partial response 14%, stable disease 27%. Subgroup analysis refractory BRAF wild-type melanoma: 2/6 patients almost complete response, prolonged stable disease. Significant inhibition of autophagy. | I | 40 | [120] |
| HCQ | Erlotinib | NSCLC (advanced, prior clinical response to EGFR-TKI) | No relevant toxicities. | I | 27 | [121] |
| HCQ | Sirolimus, Vorinostat | Advanced Cancers | Partial response: Refractory Hodgkin lymphoma; perivascular epithelioid tumor. Stable disease: Hepatocellular carcinoma, fibromyxoid sarcoma. | I | 70 | [122] |