Background
Methods
Study design
Patients
Study treatment
Endpoints and assessments
Statistical analysis
Results
Subgroup analyses: baseline characteristics
Age group | <65 years (n = 89) | ≥65 years (n = 76) | ||||
P+ L (n = 47) | L (n = 42) | P + L (n = 37) | L (n = 39) | |||
Median age (range), years | 55.0 (41–64) | 56.5 (38–64) | 72.0 (65–89) | 70.0 (65–84) | ||
ECOG performance status | ||||||
0 | 26 (55.3 %) | 23 (54.8 %) | 20 (54.1 %) | 22 (56.4 %) | ||
1 | 21 (44.7 %) | 19 (45.2 %) | 17 (45.9 %) | 17 (43.6 %) | ||
Disease stage | ||||||
IIIB | 1 (2.1 %) | 1 (2.4 %) | 1 (2.7 %) | 0 | ||
IV | 46 (97.9 %) | 41 (97.6 %) | 36 (97.3 %) | 39 (100.0 %) | ||
Disease sitea
| ||||||
Bone-only | 9 (19.2 %) | 3 (7.1 %) | 8 (21.6 %) | 9 (23.1 %) | ||
Visceral | 19 (40.4 %) | 22 (52.4 %) | 18 (48.7 %) | 21 (53.9 %) | ||
Other | 19 (40.4 %) | 17 (40.5 %) | 11 (29.7 %) | 9 (23.1 %) | ||
Prior systemic treatment | ||||||
None | 24 (51.1 %) | 23 (54.8 %) | 20 (54.1 %) | 14 (35.9 %) | ||
Yes | 23 (48.9 %) | 19 (45.2 %) | 17 (45.9 %) | 25 (64.1 %) | ||
Histological type | Ductal carcinoma (n = 117) | Lobular carcinoma (n = 37) | ||||
P+ L (n = 63) | L (n = 54) | P + L (n = 18) | L (n = 19) | |||
Median age (range), years | 63 (41–89) | 65 (42–84) | 60 (50–74) | 62 (38–78) | ||
ECOG performance status | ||||||
0 | 36 (57.1 %) | 29 (53.7 %) | 9 (50.0 %) | 14 (73.7 %) | ||
1 | 27 (42.9 %) | 25 (46.3 %) | 9 (50.0 %) | 5 (26.3 %) | ||
Disease stage | ||||||
IIIB | 2 (3.2 %) | 1 (1.9 %) | 0 | 0 | ||
IV | 61 (96.8 %) | 53 (98.1 %) | 18 (100.0 %) | 19 (100.0 %) | ||
Disease sitea
| ||||||
Bone-only | 11 (17.5 %) | 8 (14.8 %) | 4(22.2 %) | 3 (15.8 %) | ||
Visceral | 28 (44.4 %) | 30 (55.6 %) | 8 (44.4 %) | 7 (36.8 %) | ||
Other | 24 (38.1 %) | 16 (29.6 %) | 6 (33.3 %) | 9 (47.4 %) | ||
Prior systemic treatment | ||||||
None | 36 (57.1 %) | 26 (48.1 %) | 6 (33.3 %) | 7 (36.8 %) | ||
Yes | 27 (42.9 %) | 28 (51.9 %) | 12 (66.7 %) | 12 (63.2 %) | ||
Prior systemic treatment | None (n = 81) | Yes (n = 84) | ||||
P+ L (n = 44) | L (n = 37) | P + L (n = 40) | L (n = 44) | |||
Median age (range), years | 63.0 (41–83) | 62.0 (43–76) | 60.0 (46–89) | 65.5 (38–84) | ||
ECOG performance status | ||||||
0 | 26 (59.1 %) | 18 (48.6 %) | 20 (50.0 %) | 27 (61.4 %) | ||
1 | 18 (40.9 %) | 19 (51.4 %) | 20 (50.0 %) | 17 (38.6 %) | ||
Disease stage | ||||||
IIIB | 1 (2.3 %) | 0 | 1 (2.5 %) | 1 (2.3 %) | ||
IV | 43 (97.7 %) | 37 (100.0 %) | 39 (97.5 %) | 43 (97.7 %) | ||
Disease sitea
| ||||||
Bone-only | 6 (13.6 %) | 5 (13.5 %) | 11 (27.5 %) | 7 (15.9 %) | ||
Visceral | 24 (54.6 %) | 19 (51.4 %) | 13 (32.5 %) | 24 (54.6 %) | ||
Other | 14 (31.8 %) | 13 (35.1 %) | 16 (40.0 %) | 13 (29.6 %) | ||
Disease sitea
| Bone-only (n = 29) | Visceral (n = 80) | Other (n = 56) | |||
P + L (n = 17) | L (n = 12) | P + L (n = 37) | L (n = 43) | P + L (n = 30) | L (n = 26) | |
Median age (range), years | 63.0 (46–89) | 69.0 (42–73) | 63.0 (41–83) | 64.0 (38–84) | 62.0 (52–78) | 62.0 (43–75) |
ECOG performance status | ||||||
0 | 11 (64.7 %) | 10 (83.3 %) | 19 (51.4 %) | 19 (44.2 %) | 16 (53.3 %) | 16 (61.5 %) |
1 | 6 (35.3 %) | 2 (16.7 %) | 18 (48.6 %) | 24 (55.8 %) | 14 (46.7 %) | 10 (38.5 %) |
Disease stage | ||||||
IIIB | 0 | 0 | 0 | 0 | 2 (6.7 %) | 1 (3.8 %) |
IV | 17 (100.0 %) | 12 (100.0 %) | 37 (100.0 %) | 43 (100.0 %) | 28 (93.3) | 25 (96.2) |
Prior systemic treatment | ||||||
None | 6 (35.3 %) | 5 (41.7 %) | 24 (64.9 %) | 19 (44.2 %) | 14 (46.7 %) | 13 (50.0 %) |
Yes | 11 (64.7 %) | 7 (58.3 %) | 13 (35.1 %) | 24 (55.8 %) | 16 (53.3 %) | 13 (50.0 %) |
Subgroup analyses: efficacy
Age group | <65 years (n = 89) | ≥65 years (n = 76) | ||||
P+ L (n = 47) | L (n = 42) | P + L (n = 37) | L (n = 39) | |||
Median PFS (95 % CI), months | 18.8 (12.8–26.1) | 7.7 (2.8–10.9) | 26.2 (12.6–NE) | 12.9 (5.7–22.2) | ||
HR (95 % CI) | 0.315 (0.184–0.539) | 0.505 (0.269–0.948) | ||||
CBR* rate (95 % CI), % | 80.9 (66.7–90.9) | 54.8 (38.7–70.2) | 81.1 (64.8–92.0) | 61.5 (44.6–76.6) | ||
Histological type | Ductal carcinoma (n = 117) | Lobular carcinoma (n = 37) | ||||
P+ L (n = 63) | L (n = 54) | P + L (n = 18) | L (n = 19) | |||
Median PFS (95 % CI), months | 24.4 (13.1–35.3) | 11.1 (7.3–13.3) | 9.4 (7.8–18.8) | 4.8 (1.9–16.4) | ||
HR (95 % CI) | 0.393 (0.239–0.647) | 0.626 (0.282–1.391) | ||||
CBR* rate (95 % CI), % | 82.5 (70.9–90.9) | 63.0 (48.7–75.7) | 72.2 (46.5–90.3) | 42.1 (20.3–66.5) | ||
Prior systemic treatment | None (n = 81) | Yes (n = 84) | ||||
P + L (n = 44) | L (n = 37) | P + L (n = 40) | L (n = 44) | |||
Median PFS (95 % CI), months | 24.4 (13.1–35.3) | 8.2 (5.7–12.5) | 16.1 (11–NE) | 10.9 (3.5–16.6) | ||
HR (95 % CI) | 0.341 (0.194–0.599) | 0.539 (0.302–0.962) | ||||
CBR* rate (95 % CI), % | 84.1 (69.9–93.4) | 70.3 (53.0–84.1) | 77.5 (61.5–89.2) | 47.7 (32.5–63.3) | ||
Prior anti-hormone treatment (n = 55) | ||||||
P + L (n = 27) | L (n = 28) | |||||
Median PFS (95 % CI), months | NA | 18.8 (9.7–NE) | 12.9 (2.1–21.8) | |||
HR (95 % CI) | NA | 0.460 (0.222–0.956) | ||||
CBR* rate (95 % CI), % | NA | 77.8 (57.7–91.4) | 53.6 (33.9–72.5) | |||
Disease sitea
| Bone-only (n = 29) | Visceral (n = 80) | Other (n = 56) | |||
P + L (n = 17) | L (n = 12) | P + L (n = 37) | L (n = 43) | P + L (n = 30) | L (n = 26) | |
Median PFS (95 % CI), months | NE (9.4–NE) | 13.3 (1.8–NE) | 12.8 (9.7–17.2) | 7.4 (3.7–11.1) | 24.4 (18.1–35.3) | 11.2 (3.5–16.4) |
HR (95 % CI) | 0.294 (0.092–0.945) | 0.547 (0.317–0.944) | 0.402 (0.200–0.808) | |||
CBR* rate (95 % CI), % | 88.2 (63.6–98.5) | 58.3 (27.7–84.8) | 75.5 (58.5–88.2) | 60.5 (44.4–75.0) | 83.3 (65.3–94.4) | 53.8 (33.4–73.4) |
Subgroup analyses: safety
Age group | <65 years (n = 86) | ≥65 years (n = 74) | ||||
P+ L (n = 46) | L (n = 40) | P + L (n = 37) | L (n = 37) | |||
AEs (all causality), n (%) | 46 (100.0 %) | 33 (82.5 %) | 37 (100.0 %) | 32 (86.5 %) | ||
Grade 3–4 AEs (all causality), n (%) | 37 (80.4 %) | 4 (10.0 %) | 27 (73.0 %) | 12 (32.4 %) | ||
5 most common AEs that had a higher (>10 %) incidence in the P + L arm than in the L arm | Neutropenia, leukopenia, fatigue, anemia, alopecia | Neutropenia, leukopenia, fatigue, anemia, nausea | ||||
SAEs (all causality), n (%) | 7 (15.2 %) | 1 (2.5 %) | 11 (29.7 %) | 4 (10.8 %) | ||
Permanent discontinuation due to AEs (all causality), n (%) | 6 (13.0 %) | 1 (2.5 %) | 6 (16.2 %) | 1 (2.7 %) | ||
Dose reductions due to AEs (all causality), n (%) | 18 (39.1 %) | NA | 14 (37.8 %) | NA | ||
Histological type | Ductal carcinoma (n = 113) | Lobular carcinoma (n = 36) | ||||
P+ L (n = 62) | L (n = 51) | P + L (n = 18) | L (n = 18) | |||
AEs (all causality), n (%) | 62 (100.0 %) | 44 (86.3 %) | 18 (100.0 %) | 13 (72.2 %) | ||
Grade 3–4 AEs (all causality), n (%) | 47 (75.8 %) | 13 (25.5 %) | 14 (77.8 %) | 2 (11.1 %) | ||
5 most common AEs that had a higher (>10 %) incidence in the P + L arm than in the L arm | Neutropenia, fatigue, leukopenia, anemia, nausea | Neutropenia, anemia, leukopenia, asthenia, alopecia | ||||
SAEs (all causality), n (%) | 12 (19.4 %) | 5 (9.8 %) | 4 (22.2 %) | 0 | ||
Permanent discontinuation due to AEs (all causality), n (%) | 8 (12.9 %) | 1 (2.0 %) | 4 (22.2 %) | 1 (5.6 %) | ||
Dose reductions due to AEs (all causality), n (%) | 27 (43.5 %) | NA | 5 (27.8 %) | NA | ||
Prior systemic treatment | None (n = 80) | Yes (n = 80) | ||||
P+ L (n = 43) | L (n = 37) | P + L (n = 40) | L (n = 40) | |||
AEs (all causality), n (%) | 43 (100.0 %) | 32 (86.5 %) | 40 (100.0 %) | 33 (82.5 %) | ||
Grade 3–4 AEs (all causality), n (%) | 30 (69.8 %) | 5 (13.5 %) | 34 (85.0 %) | 11 (27.5 %) | ||
5 most common AEs that had a higher (>10 %) incidence in the P + L arm than in the L arm | Neutropenia, fatigue, leukopenia, anemia, alopecia | Neutropenia, leukopenia, anemia, nausea, thrombocytopenia | ||||
SAEs (all causality), n (%) | 7 (16.3 %) | 2 (5.4 %) | 11 (27.5 %) | 3 (7.5 %) | ||
Permanent discontinuation due to AEs (all causality), n (%) | 7 (16.3 %) | 1 (2.7 %) | 5 (12.5 %) | 1 (2.5 %) | ||
Dose reductions due to AEs (all causality), n (%) | 17 (39.5 %) | NA | 15 (37.5 %) | NA | ||
Disease sitea
| Bone-only (n = 28) | Visceral (n = 80) | Other (n = 52) | |||
P + L (n = 17) | L (n = 11) | P + L (n = 37) | L (n = 43) | P + L (n = 29) | L (n = 23) | |
AEs (all causality), n (%) | 17 (100.0 %) | 10 (90.9 %) | 37 100.0 %) | 36 (83.7 %) | 29 (100.0 %) | 19 (82.6 %) |
Grade 3–4 AEs (all causality), n (%) | 15 (88.2 %) | 2 (18.2 %) | 27 (73.0 %) | 12 (27.9 %) | 22 (75.8 %) | 2 (8.7 %) |
5 most common AEs that had a higher (>10 %) incidence in the P + L arm than in the L arm | Neutropenia, fatigue, leukopenia, nausea, anemia | Neutropenia, leukopenia, fatigue, anemia, decreased appetite | Neutropenia, leukopenia, anemia fatigue, hot flush | |||
SAEs (all causality), n (%) | 4 (23.5 %) | 1 (9.1 %) | 10 (27.0 %) | 3 (7.0 %) | 4 (13.8 %) | 1 (4.3 %) |
Permanent discontinuation due to AEs (all causality), n (%) | 2 (11.8 %) | 0 | 7 (18.9 %) | 1 (2.3 %) | 3 (10.3 %) | 1 (4.3 %) |
Dose reductions due to AEs (all causality), n (%) | 5 (29.4 %) | NA | 14 (37.8 %) | NA | 13 (44.8 %) | NA |
Clinical patterns of neutropenia associated with palbociclib
Palbociclib + letrozole (n = 83) | Letrozole (n = 77) | |
---|---|---|
Patients with neutropenia*, n (%)a
| ||
All Grades | 63 (75.9 %) | 4 (5.2 %) |
Grade 3 | 41 (49.4 %) | 1 (1.3 %) |
Grade 4 | 5 (6.0 %) | 0 |
Laboratory abnormality: neutrophils, n (%)‡
| ||
All Grades | 77 (93.9 %) | 13 (16.9 %) |
Grade 3 | 47 (57.3 %) | 2 (2.6 %) |
Grade 4 | 4 (4.9 %) | 0 |
Neutropenia episodes per patient, n (%)a
| ||
1 | 10 (12.1 %) | 2 (2.6 %) |
2 | 9 (10.8 %) | 1 (1.3 %) |
3–5 | 15 (18.1 %) | 0 |
≥ 6 | 29 (34.9 %) | 1 (1.3 %) |
Median time (range) from first dose to first episode of neutropenia onset, days | ||
Any grade | 20.0 (13–757) | 49.5 (15–113) |
Grade ≥3 | 28.0 (14–757) | 225.0 (225–225) |
Grade 4 | 16.0 (14–246) | – |
Total number of episodes of neutropenia in the study | ||
All Grades | 472 | 16 |
Grade ≥3 | 265 | 4 |
Grade 4 | 11 | 0 |
Median duration (range) of neutropenia by episode, days | ||
Grade ≥3 | 8 (2–58) | 30 (27–31) |
Grade 4 | 7 (3–16) | – |
Dose reductions, dose interruptions, or cycle delays due to any grade neutropenia, n (%)a
| 43 (51.8 %) | – |
Permanent discontinuation from the study due to Grade 3–4 neutropenia, n (%)a
| 5 (6.0 %) | 0 |
All Grades neutropenia with overlapping all Grades infections, n (%)b
| ||
Yes | 23 (36.5 %) | 0 |
No | 40 (63.5 %) | 4 (100.0 %) |
All Grades neutropenia with overlapping Grade 3–4 infections, n (%)b
| ||
Yes | 1 (1.6 %) | 0 |
No | 62 (98.4 %) | 4 (100.0 %) |
Grade 3–4 neutropenia with overlapping all Grades infections, n (%)c
| ||
Yes | 13 (28.2 %) | 0 |
No | 33 (71.7 %) | 1 (100.0 %) |
Grade 3–4 neutropenia with overlapping Grade 3–4 infections, n (%)c
| ||
Yes | 0 | 0 |
No | 46 (100.0 %) | 1 (100.0 %) |