Introduction
Chemotherapy
Metronomic chemotherapy
Lurbinectedin
Immunotherapy
Ipilimumab
Phase | Study | Treatment arms | Patients (n) | ORR (%) | PFS (months) | OS (months) |
---|---|---|---|---|---|---|
First line | ||||||
II | NCT01331525 | Ipilimumab + carboplatin + cisplatin; maintained with ipilimumab | 42 | 72.4 | 6.9 | 17.0 |
II | CA184-041 | Ipilimumab/placebo + carboplatin + paclitaxel vs. placebo/ipilimumab + carboplatin + paclitaxel vs. placebo + carboplatin + paclitaxel; maintained with ipilimumab vs. placebo | 128 | 32 vs. 57 vs. 49 | 5.7 vs. 6.4 vs. 5.3* (HR = 0.75, 0.64) (P = 0.11, 0.03) | 9.1 vs. 12.9 vs. 9.9 (HR = 0.95, 0.75) (P = 0.41, 0.13) |
III | CA184-156 | Ipilimumab + etoposide + cisplatin/carboplatin vs. placebo + etoposide + cisplatin/carboplatin; maintained with ipilimumab vs. placebo | 954 | 62 vs. 62 | 4.6 vs. 4.4 (HR = 0.85) (P = 0.016) | 11 vs. 10.9 (HR = 0.94) (P = 0.38) |
III | Impower-133 | Atezolizumab + carboplatin + etoposide vs. placebo + carboplatin + etoposide; maintained with atezolizumab vs. placebo | 403 | 60.2 vs. 64.4 | 5.2 vs. 4.3 (HR = 0.77) (P = 0.02) | 12.3 vs. 10.3 (HR = 0.70) (P = 0.007) |
Maintenance | ||||||
II | NCT02359019 | Pembrolizumab | 45 | 11.1 | 1.4 | 9.6 |
Relapsed | ||||||
I/II | CheckMate-032 | Nivolumab 3 mg/kg vs. nivolumab 1 mg/kg + ipilimumab 3 mg/kg vs. nivolumab 3 mg/kg + ipilimumab 1 mg/kg | 213 | 10 vs. 23 vs. 19 | 1.4 vs. 2.6 vs. 1.4 | 4.4 vs. 7.7 vs. 6.0 |
IB | KEYNOTE-028 | Pembrolizumab | 24 | 33.3 | 1.9 | 9.7 |
II | KEYNOTE-158 | Pembrolizumab | 107 | 18.7 | 2.0 | 9.1 |
I/II | NCT02261220 | Durvalumab + tremelimumab | 30 | 13.3 | 1.8 | 7.9 |
Atezolizumab
Pembrolizumab
Nivolumab
Durvalumab
Targeted therapy
Veliparib
Phase | Study | Treatment arms | Patients (n) | ORR (%) | PFS (months) | OS (months) |
---|---|---|---|---|---|---|
First line | ||||||
II | ECOG-ACRIN 2511 | Veliparib + etoposide + cisplatin vs. placebo + etoposide + cisplatin | 128 | 71.9 vs. 65.6 (P = 0.57) | 6.1 vs. 5.5 (HR = 0.75; P = 0.06) | 10.3 vs. 8.9 (HR = 0.83; P = 0.17) |
Relapsed | ||||||
II | NCT01638546 | Veliparib + temozolomide vs.placebo + temozolomide | 104 | 39 vs. 14 (P = 0.016) | 3.8 vs. 2.0 (P = 0.39) | 8.2 vs. 7.0 (P = 0.50) |
II | NCT02454972 | Lurbinectedin (PM01183) | 68 | 39.3 | 4.1 | 11.8 |
II | TRINITY | Rovalpituzumab tesirine | 177 | 16 | 4.1a | 5.6 |
II | ALTER 1202 | Anlotinib vs. placebo | 120 | 71.6 vs. 13.2b | 4.1 vs. 0.7 (HR = 0.19; P < 0.0001) | 7.3 vs. 4.9 (HR = 0.53; P = 0.0210, not yet mature) |
Rova-T
Anlotinib
Ongoing studies
Phase | Study | Treatment arms | ClinicalTrials.gov identifier | Estimated primary completion date |
---|---|---|---|---|
First line | ||||
II | REACTION | Cisplatin/carboplatin + etoposide + pembrolizumab vs. cisplatin/carboplatin + etoposide | NCT02580994 | August 2020 |
III | CASPIAN | Durvalumab+ tremelimumab+ cisplatin/carboplatin + etoposide vs. durvalumab+ cisplatin/carboplatin + etoposide vs. cisplatin/carboplatin + etoposide | NCT03043872 | September 2019 |
Maintenance | ||||
III | CheckMate-451 | Nivolumab vs. nivolumab + ipilimumab vs. placebo | NCT02538666 | October 2018 |
Relapsed | ||||
I/II | CheckMate-331 | Nivolumab vs. topotecan vs. amrubicin | NCT02481830 | August 2018 |
II | Winship3112-15 | Tremelimumab + durvalumab vs. tremelimumab + durvalumab + radiation | NCT02701400 | January 2020 |
II | AFT-17 | Pembrolizumab vs. topotecan | NCT02963090 | May 2019 |
I/II | CA001-030 | BMS-986012 vs. BMS-986012 ± nivolumab | NCT02247349 | October 2019 |
I/II | MEDIOLA | Durvalumab + olaparib vs. durvalumab + olaparib + bevacizumab | NCT02734004 | March 2023 |
Study | Main grade 3 or higher toxicities (over 10%) |
---|---|
NCT01331525 | Neurological AEs (10.3%), diarrhea (48.7%), neutrophil count decrease (23.1%), anemia (15.4%), infection (28.2%), and sepsis (10.3%). |
CA184-041 | ALT (18%) and AST (13%) in concurrent arm vs. fatigue (12%), arthralgia (10%), diarrhea (10%), neutropenia (10%), and anemia (10%) in phased arm. |
CA184-156 | Neutropenia (24%) and anemia (11%) in chemotherapy plus ipilimumab arm vs. neutropenia (14%) in chemotherapy plus placebo arm. |
Impower-133 | Neutropenia (22.7%), anemia (14.1%), decreased neutrophil count (14.1%), and thrombocytopenia (10.1%) in chemotherapy plus atezolizumab arm vs. neutropenia (24.5%), anemia (12.2%), and decreased neutrophil count (16.8%) in chemotherapy plus placebo arm. |
NCT02359019 | Most common adverse events were fatigue, nausea, cough, and dyspnea. One patient developed atrioventricular conduction block and one patient type 1 diabetes. No grade 3 to 5 treatment-related AEs was over 10% of the participants. |
CheckMate-032 | Two patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg and one patient who received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg died from treatment-related adverse events. No grade 3 to 5 treatment-related AEs was over 10% of the participants. |
KEYNOTE-028 | Treatment-related AEs were seen in 16 (66.7%) of 24 patients. Two patients experienced grade 3 to 5 treatment-related AEs. No grade 3 to 5 treatment-related AEs was over 10% of the participants. |
KEYNOTE-158 | Treatment-related AEs occurred in 63 patients (59%) and led to 4 discontinuations and 1 death (pneumonia). No grade 3 to 5 treatment-related AEs was over 10% of the participants. |
NCT02261220 | Twenty patients (67%) reported ≥ 1 treatment-related AE (TRAE); the most common were fatigue (n = 7 [23%]) and pruritus (n = 7 [23%]). Seven patients (23%) had grade 3/4 TRAEs. No patients discontinued due to TRAEs, and there were no treatment-related deaths. |
ECOG-ACRIN 2511 | Neutropenia (49%), anemia (19%), leukopenia (19%), and hyponatremia (12%) in chemotherapy plus veliparib arm vs. neutropenia (32%), anemia (12%), and leukopenia (14%) in chemotherapy plus placebo arm. |
NCT01638546 | Leukopenia (24%), lymphopenia (20%), neutropenia (31%), and thrombocytopenia (50%) in veliparib plus temozolomide arm vs. lymphopenia (26%) in temozolomide plus placebo arm. |
NCT02454972 | Neutropenia grade (44%) |
TRINITY | Thrombocytopenia (11%) |
ALTER 1202 | Grade ≥ 3 TRAEs occurred in 29 (35.8%) of patients in anlotinib arm and 6 (15.4%) in placebo arm. |