1Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
2Cancer Research Institute, The Catholic University of Korea, Seoul, Korea
3Division of Medical Oncology, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
4Division of Medical Oncology, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
5Division of Medical Oncology, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
6Division of Medical Oncology, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
7Division of Medical Oncology, Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
8Division of Medical Oncology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
9Division of Medical Oncology, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
Copyright © 2021 by the Korean Cancer Association
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Baseline patient characteristics
Characteristic | Total | Letrozole+palbociclib | Fulvestrant+palbociclib | p-value |
---|---|---|---|---|
No. of patients | 169 | 145 | 24 | |
Age (yr) | ||||
Median (range) | 57.0 (37–92) | 58.0 (37–92) | 53.5 (38–72) | 0.025 |
≤ 65 | 129 (76.3) | 106 (73.1) | 23 (95.8) | 0.020 |
> 65 | 40 (23.7) | 39 (26.9) | 1 (4.2) | |
ECOG PS | ||||
0 | 89 (52.7) | 74 (51.0) | 15 (62.5) | 0.668 |
1 | 58 (34.3) | 52 (35.9) | 6 (25.0) | |
2 | 20 (11.8) | 17 (11.7) | 3 (12.5) | |
3 | 2 (1.2) | 2 (1.4) | 0 | |
Histology | ||||
Invasive ductal carcinoma | 135 (79.9) | 116 (80.0) | 19 (79.2) | 0.933 |
Invasive lobular carcinoma | 12 (7.1) | 11 (7.6) | 1 (4.2) | |
Mixed | 2 (1.2) | 2 (1.4) | 0 | |
Mucinous | 5 (3.0) | 4 (2.8) | 1 (4.2) | |
Others | 9 (5.3) | 7 (4.8) | 2 (8.3) | |
Unknown | 6 (3.6) | 5 (3.4) | 1 (4.2) | |
Estrogen receptor | ||||
Positive | 168 (99.4) | 145 (100) | 23 (95.8) | 0.304 |
Negative | 1 (0.6) | 0 | 1 (4.2) | |
Progesterone receptor | ||||
Positive | 138 (81.7) | 116 (80.0) | 22 (91.7) | 0.193 |
Negative | 29 (17.2) | 27 (18.6) | 2 (8.3) | |
Unknown | 2 (1.2) | 2 (1.4) | 0 | |
Luminal | ||||
A | 54 (32.0) | 45 (31.0) | 9 (37.5) | 0.677 |
B | 70 (41.4) | 62 (42.8) | 8 (33.3) | |
Unknown | 45 (26.6) | 38 (26.2) | 7 (29.2) | |
Stage at initial diagnosis | ||||
I | 22 (13.0) | 16 (11.0) | 6 (25.0) | 0.850 |
II | 39 (23.1) | 32 (22.1) | 7 (29.2) | |
III | 37 (21.9) | 33 (22.8) | 4 (16.7) | |
IV | 63 (37.3) | 57 (39.3) | 6 (25.0) | |
Not assessed | 8 (4.7) | 7 (4.8) | 1 (4.2) | |
Prior neoadjuvant and adjuvant chemotherapy | ||||
Systemic chemotherapy | 83 (78.3) | 68 (77.3) | 15 (83.4) | 0.764 |
Neoadjuvant and adjuvant chemotherapy | 13 (12.3) | 10 (11.4) | 3 (16.7) | |
Neoadjuvant chemotherapy | 5 (4.7) | 5 (5.7) | 0 | |
Adjuvant chemotherapy | 65 (61.3) | 53 (60.2) | 12 (66.7) | |
Not done | 22 (20.8) | 19 (21.6) | 3 (16.7) | |
Not assessed | 1 (0.9) | 1 (1.1) | 0 | |
Endocrine resistance | ||||
No | 59 (34.9) | 59 (40.7) | 0 | < 0.001 |
Yes | 54 (32.0) | 30 (20.7) | 24 (100) | |
De novo | 55 (32.5) | 55 (37.9) | 0 | |
NA | 1 (0.6) | 1 (0.7) | 0 | |
Menopause | ||||
Postmenopausal | 164 (97.0) | 143 (98.6) | 21 (87.5) | 0.012 |
Natural menopause | 126 (74.6) | 110 (75.9) | 16 (66.7) | |
Prior BSO | 38 (22.5) | 33 (22.8) | 5 (20.8) | |
Premenopausal | 5 (3.0) | 2 (1.4) | 3 (12.5) | |
No. of metastatic sites | ||||
1 | 57 (33.7) | 49 (33.8) | 8 (33.3) | 0.927 |
2 | 54 (32.0) | 47 (32.4) | 7 (29.2) | |
≥ 3 | 58 (34.3) | 49 (33.8) | 9 (37.5) | |
Presence of visceral metastasis | ||||
Yes | 93 (55.0) | 77 (53.1) | 16 (66.7) | 0.310 |
No | 76 (45.0) | 68 (46.9) | 8 (33.3) | |
Liver metastasis | ||||
Yes | 35 (20.7) | 22 (15.2) | 13 (54.2) | < 0.001 |
No | 134 (79.3) | 123 (84.8) | 11 (45.8) | |
Lung metastasis | ||||
Yes | 66 (39.1) | 58 (40.0) | 8 (33.3) | 0.693 |
No | 103 (60.9) | 87 (60.0) | 16 (66.7) | |
Bone only metastasis | ||||
Yes | 20 (11.8) | 17 (11.7) | 3 (12.5) | > 0.99 |
No | 149 (88.2) | 128 (88.3) | 21 (87.5) | |
RT during palbociclib administration | ||||
Yes | 28 (16.6) | 24 (16.6) | 4 (16.7) | > 0.99 |
No | 141 (83.4) | 121 (83.4) | 20 (83.3) |
Values are presented as number (%) unless otherwise indicated. BSO, bilateral salphingo-oophorectomy; ECOG PS, Eastern Cooperative Oncology Group performance status; NA, not applicable; RT, radiation therapy.
Systemic treatment before palbociclib in recurrent and metastatic breast cancer
Letrozole + palbociclib | Fulvestrant + palbociclib | |
---|---|---|
First line | 136 (93.8) | 0 |
Second line | 3 (2.1) | 7 (29.2) |
Third line | 1 (0.7) | 8 (33.3) |
Fourth line and beyond | 5 (3.4) | 9 (37.5) |
Previous systemic treatment for recurrent and metastatic breast cancer before palbociclib use | ||
Cytotoxic chemotherapy | 8 | 14 |
Anthracycline | 8 (100) | 6 (42.9) |
Docetaxel | 8 (100) | 10 (71.4) |
Paclitaxel | 2 (25.0) | 4 (28.6) |
nab-paclitaxel | 1 (12.5) | 1 (7.1) |
Capecitabine | 4 (50.0) | 7 (50.0) |
Eribulin | 3 (37.5) | 5 (35.7) |
Gemcitabine | 2 (18.2) | 5 (35.7) |
Vinorelbine | 0 | 1 (7.1) |
CMF |
2 (25.0) | 1 (7.1) |
Endocrine treatment | 2 | 24 |
Letrozole | 0 | 17 (70.8) |
Anastrozole | 0 | 5 (35.7) |
Exemestane | 0 | 4 (19.0) |
Exemestane+everolimus | 0 | 5 (35.7) |
Tamoxifen | 2 (100) | 6 (25.0) |
Values are presented as number (%).
a)CMF: cyclophosphamide+ methotrexate+5-fluorouracil.
Previous endocrine treatment and pattern of resistance in patients with recurrent breast cancer
Total | Letrozole+palbociclib | Fulvestrant+palbociclib | p-value | |
---|---|---|---|---|
No. of patients | 106 | 88 | 18 | |
Adjuvant endocrine treatment | ||||
Refused | 8 (7.5) | 8 (9.1) | 0 | 0.167 |
Yes | 91 (85.8) | 73 (83.0) | 18 (100) | |
Not assessed | 7 (6.6) | 7 (8.0) | 0 | |
Regimen | ||||
Tamoxifen | 63 (69.2) | 51 (73.9) | 12 (75.0) | 0.615 |
Letrozole | 5 (5.5) | 3 (4.3) | 2 (12.5) | |
Anastrozole | 12 (13.2) | 10 (14.5) | 2 (12.5) | |
Tamoxifen followed by AI | 6 (6.6) | 4 | 2 | |
Toremifene | 2 (2.2) | 2 (2.9) | 0 | |
Unknown | 3 (3.3) | 3 (4.3) | 0 | |
Completion of adjuvant treatment | ||||
No | 46 (50.5) | 35 (47.9) | 11 (61.1) | 0.461 |
Yes | 45 (49.5) | 38 (52.1) | 7 (38.9) | |
Duration of treatment (yr) | ||||
Median (range) | 4.6 (0.94–9.88) | 4.7 (0.94–9.88) | 4.0 (1.67–7.27) | 0.142 |
Endocrine resistance | ||||
No | 59 (55.7) | 59 (67) | 0 | 0.021 |
Yes | 46 (43.4) | 28 (31.8) | 18 (100) | |
Primary resistance | 7 (15.2) | 4 (14.3) | 3 (16.7) | |
Secondary resistance | 35 (84.8) | 24 (85.7) | 15 (83.3) | |
NA | 1 (0.9) | 1 (1.1) | ||
Menopausal state | ||||
Postmenopausal | 102 (96.2) | 86 (97.7) | 16 (88.9) | 0.161 |
Natural menopause | 83 (78.3) | 69 (78.4) | 14 (77.8) | |
Prior BSO | 19 (17.9) | 17 (19.3) | 2 (11.1) | |
Premenopausal | 4 (3.8) | 2 (2.3) | 2 (11.1) | |
Disease-free survival (mo) | ||||
Median (range) | 26.17 (0–247.77) | 36.03 (0–247.77) | 0.72 (0–56.10) | 0.014 |
Values are presented as number (%) unless otherwise indicated. AI, aromatase inhibitor; BSO, bilateral salphingo-oophorectomy; NA, not applicable.
Best overall response in patients with measurable disease
Letrozole + palbociclib | Fulvestrant + palbociclib | |
---|---|---|
Best response | ||
Partial response | 55 (39.6) | 6 (28.6) |
Stable disease | 69 (49.6) | 11 (52.4) |
Progressive disease | 11 (7.9) | 4 (19.0) |
Not assessed | 4 (2.9) | 0 |
Overall response rate | 55 (39.6) | 6 (28.6) |
Disease control rate | 124 (89.2) | 17 (81.0) |
Survival outcome (mo) | ||
Median PFS (95% CI) | 25.6 (19.1 to NA) | 6.37 (5.33 to NA) |
Values are presented as number (%) unless otherwise indicated. CI, confidence interval; NA, not available; PFS, progression-free survival.
Concurrent radiation and palbociclib administration
Total | Letrozole+palbociclib | Fulvestrant+palbociclib | |
---|---|---|---|
Concurrent radiation | |||
Yes | 28 (16.6) | 24 (16.6) | 4 (16.7) |
No | 141 (83.4) | 121 (83.4) | 20 (83.3) |
Age during radiation treatment (yr) | |||
Median (range) | 58 (38–92) | 58 (38–92) | 47 (38–62) |
ECOG | |||
0 | 16 (57.1) | 14 (58.3) | 2 (50.0) |
1 | 8 (28.6) | 7 (29.2) | 1 (25.0) |
2 | 4 (14.3) | 3 (12.5) | 1 (25.0) |
Radiation site (radiation dose, Gy) | |||
Bone: axial skeleton (24–36 Gy) | 14 (50.0) | 13 (54.2) | 1 (25.0) |
Bone: pelvis (30 Gy) | 6 (21.4) | 4 (16.7) | 2 (50.0) |
Bone: extremity (30 Gy) | 6 (21.4) | 6 (25.0) | 0 |
Thorax: sterum, chest wall, IMN (24–54Gy) | 8 (28.5) | 8 (33.3) | 0 |
Breast (50 Gy) | 5 (17.9) | 5 (20.8) | 0 |
Lung (48 Gy) | 1 (3.6) | 0 | 1 (25.0) |
Brain (30 Gy) | 2 (7.1) | 1 (4.2) | 1 (25.0) |
RT technique | |||
SBRT | 6 (21.4) | 4 (16.7) | 2 (50.0) |
3D-CRT | 21 (75) | 19 (79.2) | 2 (50.0) |
SBRT+3D-CRT | 1 (3.6) | 1 (4.1) | 0 |
G3–4 Neutropenia during RT | |||
Yes | 12 (42.9) | 11 (45.8) | 1 (25.0) |
Grade 3 | 8 (28.6) | 8 (33.3) | 0 |
Grade 4 | 4 (14.3) | 3 (12.5) | 1 (25.0) |
No | 16 (57.1) | 13 (54.2) | 3 (75.0) |
Interruption of palbociclib | |||
No | 24 (85.7) | 21 (87.5) | 3 (75.0) |
Yes | 4 (14.3) | 3 (12.5) | 1 (25.0) |
Delay of palbociclib | |||
No | 13 (46.4) | 10 (41.7) | 3 (75.0) |
Yes | 15 (53.6) | 14 (58.3) | 1 (25.0) |
Duration, median (day) | 7 (5–15) | 7 (5–14) | 15 |
Initial palbociclib dose | |||
125 mg | 19 (67.9) | 18 (75.0) | 1 (25.0) |
100 mg | 8 (28.6) | 5 (20.8) | 3 (75.0) |
75 mg | 1 (3.6) | 1 (4.1) | 0 |
Palbociclib dose after RT | |||
125 mg | 13 (46.4) | 13 (54.2) | 0 |
100 mg | 11 (39.3) | 7 (29.3) | 4 (100) |
75 mg | 4 (14.3) | 4 (16.6) | 0 |
Dose reduction of palbociclib | |||
No | 19 (67.9) | 16 (66.7) | 3 (75.0) |
Yes | 9 (32.1) | 8 (33.3) | 1 (25.0) |
125 mg → 100 mg | 6 (21.4) | 5 (20.8) | 1 (25.0) |
100 mg → 75 mg | 3 (10.7) | 3 (12.5) | 0 |
Values are presented as number (%) unless otherwise indicated. 3D-CRT, 3-dimensional conformal radiation therapy; ECOG, Eastern Cooperative Oncology Group; IMN, internal mammary lymph node; RT, radiation therapy; SBRT, stereotactic body radiation therapy.
Treatment related adverse events
Letrozole+palbociclib (n=145) | Fulvestrant+palbociclib (n=24) | |||||
---|---|---|---|---|---|---|
|
| |||||
Any grade | Grade 3 | Grade 4 | Any grade | Grade 3 | Grade 4 | |
Hematologic | ||||||
| ||||||
Anemia | 39 (26.8) | 9 (6.2) | 1 (0.7) | 10 (41.7) | 1 (4.2) | 0 |
| ||||||
Neutropenia | 135 (93.1) | 101 (69.7) | 24 (16.6) | 23 (95.8) | 9 (37.5) | 11 (45.8) |
| ||||||
Thrombocytopenia | 46 (31.7) | 8 (5.5) | 2 (1.4) | 12 (50.0) | 3 (12.5) | 1 (4.2) |
| ||||||
Non-hematologic | ||||||
| ||||||
Mucositis | 37 (25.5) | 0 | 0 | 2 (8.3) | 0 | 0 |
| ||||||
Diarrhea | 6 (4.1) | 2 (1.4) | 0 | 0 | 0 | 0 |
| ||||||
Constipation | 5 (3.4) | 0 | 0 | 0 | 0 | 0 |
| ||||||
Fatigue | 39 (26.9) | 0 | 0 | 7 (29.2) | 0 | 0 |
Values are presented as number (%).
Values are presented as number (%) unless otherwise indicated. BSO, bilateral salphingo-oophorectomy; ECOG PS, Eastern Cooperative Oncology Group performance status; NA, not applicable; RT, radiation therapy.
Values are presented as number (%). CMF: cyclophosphamide+ methotrexate+5-fluorouracil.
Values are presented as number (%) unless otherwise indicated. AI, aromatase inhibitor; BSO, bilateral salphingo-oophorectomy; NA, not applicable.
Values are presented as number (%) unless otherwise indicated. CI, confidence interval; NA, not available; PFS, progression-free survival.
Values are presented as number (%) unless otherwise indicated. 3D-CRT, 3-dimensional conformal radiation therapy; ECOG, Eastern Cooperative Oncology Group; IMN, internal mammary lymph node; RT, radiation therapy; SBRT, stereotactic body radiation therapy.
Values are presented as number (%).