Table 1.
Key reported clinical trials with palbociclib and abemaciclib.
| Study name/ID | Combination drug | Phase | Population | Common Grade 3/4 AEs (≥10% of patients) | Clinical activity |
|---|---|---|---|---|---|
| Palbociclib | |||||
| Breast Cancer | |||||
| PALOMA-1/NCT00721409 (74) | Letrozole | II | ER+ ABC with no prior treatment for ABC (N=165) | Neutropenia (54%), leukopenia (19%) | Median PFS 20.2 months vs 5.7 months for letrozole monotherapy (HR=0.488; P=0.0004) |
| PALOMA-2/NCT01740427 (18) | Letrozole | III | ER+ ABC with no prior treatment for ABC (N=666) | Neutropenia (66%), leukopenia (25%) | Median PFS 24.8 months vs 14.5 months for letrozole monotherapy (HR=0.58; P<0.000001) |
| PALOMA-3/NCT01942135 (19) | Fulvestrant | III | HR+ ABC after progression on one line of endocrine therapy for ABC (N=521) | Neutropenia (62%), leukopenia (25%) | Median PFS 9.2 months vs 3.8 months for fulvestrant monotherapy (HR=0.42; P<0.001) |
| NCT01037790 (75) | None | II | Metastatic Rb+ breast cancer (N=37; n=33 HR+) | Neutropenia (54%), leukopenia (51%), lymphopenia (30%), thrombocytopenia (19%) |
Total (N=37): 5% PR, 38% SD <6months, 14% SD ≥6 months, CBR 19% HR+ (n=33): 6% PR, 39% SD <6 months, 16% SD ≥6 months, CBR: 21% |
| Solid tumors | |||||
| NCT00141297 (71) | None | I | Rb+ advanced solid tumors (N=41) | Neutropenia (20%), leukopenia (10%) in Cycle 1 | 27% SD for ≥4 cycles, 16% SD for ≥10 cycles (n=37 evaluable) |
| MCL | |||||
| NCT00420056 (76) | None | Ib | CD19+/CD20+, CD5+, CD23− MCL, with cyclin D1 positivity, t(11;14) translocation, or bcl-1/IgH rearrangement (N=17) | Neutropenia (35%), thrombocytopenia (24%), hypophosphatemia (12%) | 6% CR, 12% PR, 41% SD, median PFS 4 months (90% CI 2.0–14.7 months) (n=16 evaluable) |
| Liposarcoma | |||||
| NCT01209598 (77) | None | II | Advanced CDK4− amplified, Rb+ well-differentiated or dedifferentiated liposarcoma (N=30) | Neutropenia (50%), leukopenia (47%), thrombocytopenia (30%), lymphopenia (27%), anemia (17%) | 3% PR, 12-week PFS 66% (90% CI 51–100%), median PFS 18 weeks (n=29 evaluable) |
| NSCLC | |||||
| NCT01291017 (78) | None | II | Previously treated, advanced Rb+, CDKN2A inactivated NSCLC (N=19) | Neutropenia (16%) | 50% SD, median PFS 12.5 weeks |
| Abemaciclib | |||||
| Solid tumors | |||||
| NCT01394016 (79) | None | I | Advanced solid tumors (whole study N=225; escalation phase n=33) | Leukopenia (10%), neutropenia (10%) (n=173) |
Breast cancer (n=47): 23% PR, 47% SD, 23% ORR, 49% CBR, 70% DCR, median PFS 5.8 months NSCLC (n=68): 3% PR, 46% SD, 3% ORR, 49% DCR, median PFS 2 months Melanoma (n=26): 4% PR, 23% SD, 4% ORR, 27% DCR Glioblastoma (n=17): 0% PR, 18% SD, 0% ORR, 18% DCR CRC (n=15): 0% PR, 13% SD, 0% ORR, 13% DCR |
| NCT02014129 (80) | None | I | Japanese patients with advanced cancer (N=12) | 200 mg BID (n=6): leukopenia (33%), neutropenia (17%) | Maximal percent change in tumor size from baseline: −35 to +25% >30% tumor shrinkage in 2 patients (HR−, HER2+ breast cancer and small intestine neuroendocrine carcinoma) |
| Breast cancer | |||||
| MONARCH-1/NCT02102490 (22) | None | II | HR+, HER2− ABC that has progressed on prior endocrine therapy and chemotherapy (N=132) | Diarrhea (20%) and fatigue (13%), white blood cell decreased (28%), neutrophil count decrease (22%) | Confirmed PR 20%, confirmed ORR 20%, CBR 42%, median PFS 6 months |
| NCT02057133 (81) | Endocrine and HER2-targeted therapies | Ib | HR+ metastatic breast cancer (N=110) |
Combination with letrozole (n=20): diarrhea (45%), fatigue (20%), neutropenia (20%), nausea (15%), vomiting (10%) Combination with anastrozole (n=16): diarrhea (31%), leukocyte count reduced (31%), neutrophil count reduced (25%), lymphocyte count reduced (25%), fatigue (19%) Combination with tamoxifen (n=16): diarrhea (31%), fatigue (31%), lymphocyte count reduced (13%), leukocyte count reduced (13%) Combination with exemestane (n=15): diarrhea (27%), abdominal pain (20%), neutrophil count reduced (20%), lymphocyte count reduced (20%), fatigue (13%) Combination with exemestane + everolimus (150 mg BID dose; n=15): neutrophil count reduced (33%), leukocyte count reduced (33%), lymphocyte count reduced (33%), diarrhea (27%), anemia (20%), fatigue (13%), stomatitis (13%), hypokalemia (13%) Combination with exemestane + everolimus (200 mg BID dose; n=4): neutrophil count reduced (75%), diarrhea (25%), leukocyte count reduced (25%), platelet count reduced (25%) Combination with trastuzumab (150 mg BID dose; n=18): diarrhea (17%), fatigue (11%), hypokalemia (11%), lymphocyte count reduced (11%) Combination with trastuzumab (200 mg BID dose; n=6): diarrhea (83%), anemia (33%), neutrophil count reduced (33%), leukocyte count reduced (33%), lymphocyte count reduced (33%), platelet count reduced (17%), fatigue (17%), abdominal pain (17%) |
Combination with letrozole (n=20): 6-month PFS 76% Combination with anastrozole (n=16): 6-month PFS 87% Combination with tamoxifen (n=16): 6-month PFS 73% Combination with exemestane (n=15): 6-month PFS 75% Combination with exemestane + everolimus (150 mg BID dose; n=15): 6-month PFS 89% Combination with exemestane + everolimus (200 mg BID dose; n=4): 6-month PFS 100% Combination with trastuzumab (150 mg BID dose; n=18): 6-month PFS 29% (HR+ breast cancer; n=11); 38% (HR− breast cancer; n=7) Combination with trastuzumab (200 mg BID dose; n=6): 6-month PFS 50% (HR+ breast cancer; n=5); 0 (HR− breast cancer; n=1) |
| NCT01394016 (79) | None | I | Metastatic breast cancer expansion cohort (N=47) | – |
All (N=47): 23% PR, 47% SD, DCR 70%, median PFS 5.8 months HR+ (n=36): 31% PR, 50% SD, DCR 81%, median PFS 8.8 months |
| NCT01394016 (79) | Fulvestrant | I | HR+ ABC (N=19) | Neutropenia (32%), leukopenia (26%), abdominal pain (11%), anemia (11%) | 21% PR, ORR 21%, DCR 79%, CBR 63% |
| NSCLC | |||||
| NCT01394016 (79) | None | I | NSCLC expansion cohort (N=68) | – |
All NSCLC (N=68): 3% PR, 46% SD, 49% DCR, median PFS 2 months KRAS-mutant NSCLC (n=29): 3% PR, 31% SD ≥24 weeks, 55% DCR, median PFS 2.8 months KRAS-wildtype NSCLC (n=33): 3% PR, 12% SD ≥24 weeks, 39% DCR, median PFS 1.9 months |
BID, twice daily; CBR, clinical benefit rate; CDKN2A, cyclin-dependent kinase inhibitor 2A; CI, confidence interval; CR, complete response; CRC, colorectal cancer; DCR, disease control rate; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; HER2+, HER2-positive; HR, hazard ratio; KRAS, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog; MCL, mantle cell lymphoma; MRT, malignant rhabdoid tumor; NSCLC, non-small cell lung cancer; ORR, overall response rate; Rb+, Rb-positive.