Table 4 Selected clinical trials of combination therapy
From: Angiogenic signaling pathways and anti-angiogenic therapy for cancer
Interventions | Cancers | Phase | Results | NCT numbers |
|---|---|---|---|---|
Successful clinical trials | ||||
ABI-007 plus bevacizumab vs. ABI-007 | Metastatic BC | II | Promising PFS and an acceptable safety profile with no unanticipated toxicities (combination vs. ABI-007: PFS 11.4 vs. 6.11 months, ORR 30% vs. 14%)a | NCT00394082 |
Docetaxel plus ramucirumab vs. plus placebo | Locally advanced or metastatic urothelial carcinoma | III | This combination significantly prolongs PFS with no unexpected toxic effects; PFS 4.07 vs. 2.76 monthsa. | NCT02426125 |
Cisplatin or carboplatin, and etoposide plus sunitinib | Extensive-stage small cell lung cancer | I/II | The addition of sunitinib prolongs PFS and OS; median OS (9.0 vs. 6.9 months) and median PFS (3.7 vs. 2.1 months)a. | NCT00453154 |
Docetaxel plus vandetanib vs. plus placebo | Advanced NSCLC | III | This combination significantly improves PFS, median PFS 4.0 vs. 3.2 monthsa. | NCT00312377 |
Bevacizumab, carboplatin, paclitaxel plus atezolizumab (ABCP) vs. BCP | Stage IV non-squamous NSCLC | III | The addition of atezolizumab to bevacizumab plus chemotherapy is significant: median PFS 8.3 vs. 6.8 months; median OS 19.2 vs. 14.7 monthsa. | NCT02366143 |
Atezolizumab plus bevacizumab vs. sorafenib | Untreated locally advanced or metastatic HCC | III | Atezolizumab-bevacizumab is better than sorafenib: OS at 12 months 67.2% vs. 54.6%; median PFS 6.8 vs. 4.3 monthsa. | NCT03434379 |
Different chemotherapies (nab-paclitaxel; paclitaxel; gemcitabine/carboplatin) plus pembrolizumab | Untreated locally recurrent inoperable or metastatic TNBC | III | The addition of pembrolizumab resulted in significantly longer PFS and OS than chemotherapy-placebo in twice interim analysisb. | NCT02819518 |
Lenvatinib plus pembrolizumab vs. doxorubicin | Advanced endometrial cancer after failure of platinum-based chemotherapy | III | The combination has significantly longer PFS and OS: median PFS 6.6 vs. 3.8 months; median OS 17.4 vs. 12.0 monthsb. | NCT03517449 |
Atezolizumab with or without cobimetinib vs. regorafenib | Metastatic CRC | II | Positive results in median OS: atezolizumab 7.10 months, atezolizumab plus cobimetinib 8.87 months, regorafenib 8.51 monthsa. | NCT02788279 |
Unsuccessful or terminated clinical trials | ||||
Irinotecan and temozolomide plus bevacizumab | Relapsed or refractory neuroblastoma | II | Expected and transient toxicities, but the addition of bevacizumab did not improve response rates compared to irinotecan plus temozolomidea. | NCT01114555 |
FOLFOX6 plus bevacizumab | Biliary system carcinoma | II | 1/8 patient with perforation of colon; impossible to get insurance companies to cover bevacizumabc. | NCT00881504 |
Ixabepilone plus bevacizumab | Metastatic RCC | II | Well tolerated, with modest activity in second - or later-line mRCC, not recommendeda. | NCT00923130 |
Docetaxel plus sorafenib | Advanced non-squamous cell NSCLC | II | Preliminary efficacy data was not encouraging, 4/5 patients with serious adverse eventsc. | NCT00801801 |
Temozolomide plus sorafenib | Recurrent GBM | II | Well tolerated, but limited activity for recurrent GBMa. | NCT00597493 |
Paclitaxel and carboplatin plus axitinib vs. plus bevacizumab | Advanced lung cancer | II | Axitinib plus paclitaxel and carboplatin is worse than bevacizumab plus paclitaxel and carboplatin: PFS 11.0 vs. 15.9 months; OS 18.1 vs. 21.6 monthsa. | NCT00600821 |
Modified FOLFOX6 plus axitinib and/or bevacizumab | Metastatic CRC | II | No improvements in combination with axitinib or axitinib/bevacizumab compared to bevacizumab plus FOLFOX6: PFS 11.0 vs. 12.5 vs.15.9 months; OS 18.1 vs. 19.7 vs. 21.6 monthsa. | NCT00460603 |
Chemotherapy (capecitabine or docetaxel) vs. sunitinib | TNBC | II | No improvements of sunitinib in median OS (9.4 vs. 10.5 months), objective response rates (3% vs. 7%)a. | NCT00246571 |
Docetaxel plus vandetanib vs. plus placebo | Transitional bladder cancer | II | The additional of vandetanib not significantly improve the outcomes: median PFS 2.56 vs. 1.58 months; OS and ORR with no differencea. | NCT00880334 |
Azacitidine plus durvalumab vs. azacitidine | Untreated adults with higher-risk MDS or elder patients with AML | II | More toxicities and without significant improvement in clinical outcomes than azacitidinea. | NCT02775903 |
Gemcitabine and nab-paclitaxel vs. gemcitabine, nab-paclitaxel plus durvalumab and tremelimumab | Metastatic pancreatic adenocarcinoma | II | No significant benefits from the addition of durvalumab and tremelimumabb. | NCT02879318 |
Gemcitabine plus axitinib vs. gemcitabine | Metastatic pancreatic cancer | II | Similar safety; non-statistically significant gain in OS than gemcitabine alone: 6.9 vs. 5.6 monthsa. | NCT00219557 |
