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. Author manuscript; available in PMC: 2017 Jun 20.
Published in final edited form as: Discov Med. 2016 Jan;21(113):65–74.

Table 2.

Clinical trials of single-agent CDK 4/6 inhibitors

Study drug NCT number/reference Phase Patient population Safety Clinical activity
Palbociclib NCT00141297/ (Flaherty et al., 2012) I Advanced solid tumors n = 41

  • DLTs observed in 5 (12%) patients

  • Hematologic AEs after Cycle 1: G3 neutropenia (12%), anemia (7%), and leukopenia (2%)

  • Most common (>10%) non-hematologic AEs after Cycle 1: fatigue (24%), diarrhea (15%) and nausea, dyspnea, arthralgia (12% each)

  • SD >2 cycles: 35% of patients

  • SD ≥4 cycles: 27% of patients

  • SD ≥10 cycles: 16.2% of patients, including 1 patient with breast cancer
NCT01037790/ (DeMichele et al., 2015) II Refractory solid tumors n = 37 (MBC cohort)

  • G3/4 toxicities: transient neutropenia (51%), thrombocytopenia (22%) and anemia (5%)

  • One episode of neutropenic sepsis occurred in Cycle 1 in patient with 6 prior chemotherapy regimens

  • Cytopenias managed by dose reduction

  • All non-hematological toxicities were G1/2

 Overall (n = 37)

  • PR: 5% (2/37)

  • SD <6 months: 38% (14/37)

  • SD ≥6 months: 14% (5/37)

  • PD: 43% (16/37)

  • PFS: 3.7 months

HR+ patients (n = 33)

  • PR: 6% (2/33)

  • SD <6 months: 39% (13/33)

  • SD ≥6 months: 16% (5/33)

  • PD: 39% (13/33)

  • PFS: 3.8 months
Ribociclib NCT01237236/ (Infante et al., 2014) I Advanced solid tumors or lymphomas n = 128

  • Most common (>10%) treatment-related G3/4 AEs: neutropenia (29%), leukopenia (21%), and lymphopenia (18%)

 Three PRs:

  • One patient with a head and neck acinar carcinoma and CDKN2A loss

  • One patient with PIK3CA-mutant, CCND1-amplified estrogen receptor-positive breast cancer

  • One patient with BRAF/NRAS wild-type, CCND1-amplified melanoma
Abemaciclib NCT01394016/ (Shapiro et al., 2013; Patnaik et al., 2014) I Advanced cancer (NSCLC, glioblastoma, breast cancer, melanoma, and colorectal cancer) n = 55

  • The most common (>10%) study drug-related AEs were diarrhea (52%, including 5% G3), nausea (30%, 4% G3), fatigue (21%, 7% G3), vomiting (18%, 2% G3), and neutropenia (16%, 7% G3)

  • One patient with ovarian cancer had a durable CA-125 response with >50% decrease for 16 cycles

  • One patient with KRAS mutant NSCLC had a 27% decrease by RECIST

  • One patient with CDKN2A−/− NRAS mutant melanoma had a confirmed PR

MBC (n = 47)

  • Confirmed PR: 9

  • SD: 24

  • PD: 11

  • DCR: 70%

  • PFS: 5.8 months

HR+ MBC (n = 36)

  • Confirmed PR: 9

  • ORR: 25%

  • SD: 20

  • DCR: 81%

  • PFS: 9.1 months

AE adverse event, DCR disease control rate, DLT dose-limiting toxicity, G Grade, HR+ hormone receptor-positive, MBC metastatic breast cancer, NSCLC non-small cell lung cancer, ORR overall response rate, PD progressive disease, PFS progression-free survival, PR partial response, RECIST Response Evaluation Criteria In Solid Tumors, SD stable disease