Table 2.
Real-life studies with palbociclib in advanced breast cancer (ABC).
| Author (Ref) | Pts N/mean age | Postmenopausal status | Prior F500/EVE | Treatment line | Combined drug | Metastatic sites | Outcome | Toxicity (any grade) |
Toxicity (G3–G4) |
|---|---|---|---|---|---|---|---|---|---|
| Li et al.33* | 1242/62.7 | 100% | 12.4%/NA | 1st: 37% 2nd: 32% 3rd: 19% 4th: 12% |
NA | Liver 15.8% Lung 15.5% Bone and bone marrow 72.1% |
Dose reduction rate: 6.3–9.6% at 1 mo 23.1–25.3% at 3 mo 29.1–31.5% at 6 mo 31.9–33.7% at 12 mo |
NA | NA |
| Ban et al.27* | 24/52.7 | 71% | 70.8%/4.1% | >4 | AI | Visceral and bone 58.3% Bone-only 29.1% Visceral 12.5% |
SD 58.3% ORR 0% mPFS 4.8 mo mOS 11 mo |
Neutropenia 75% Anemia 50% Thrombocytopenia 41.6% Nausea 12.5% Stomatitis 8.3% Epistaxis 4.1% |
Neutropenia 66.6% Thrombocytopenia G3 12.5% |
| Bui et al.36* | 46/67 | 85% | 17%/12.5% | ≥3 ET line 28% | F500 AI |
Visceral 61% Lung 94% Liver 43% Brain or pleural 9% |
mPFS 10 mo | NA | NA |
| Darden et al.38§ | 604/41 | NA | NA | NA | AI 41.4% F500 58.6% |
Visceral 51.3% No visceral 48.7% |
Treatment satisfaction according to CTSQ | NA | NA |
| Dhakal et al.28* | 23/68 | 95% | NA/100% | NA | NA | Visceral 83% | ORR 0% CRB 17.4% mPFS 2.9 mo mOS 19.8 mo |
NA | NA |
| Du Rusquec et al.24§ | 60/61 | NA | 46.7%/100% | NA | F500 100% | Visceral 83.3% Bone-only 16.7% |
PR 26.7% SD 45% PD 28.3% mPFS 5.8 mo mOS NR |
Neutropenia 93.3% Anemia 65% Thrombocytopenia 55% Febrile neutropenia 3.3% Fatigue 16.7% Nausea 3.3% Stomatitis 3.3% Hypertransaminasemia 1.7% |
Neutropenia 73.4% Anemia G3 5.0% Thromocytopenia 11.6% Febrile neutropenia G4 1.7% Fatigue 3.3% Stomatitis 1.7% |
| Gong et al.34* | 100/61 | 86% | 17%/NA | 1st–2nd:29% 3rd–4th: 52% ≥5th: 19% |
LET 69% F500 17% Other 14% |
NA | Dose modification 38% Dose changes 18.4% |
Neutropenia 59.6% Anemia NA Thrombocytopenia 11.8% Fatigue 4.8% Mucositis 9.5% Acute kidney injury 2.4% |
Neutropenia 54.8% Anemia G3 2.4% Thrombocytopenia G3 2.4% Fatigue G3 2.4% Mucositis G3 2.4% Pneumonitis G3 2.4% Septic shock 2.4% |
| Hoste et al.25* | 82/67.1 | 100% | NA | ≥4 | LET 89% F500 3.7% TAM 2.4% Other AI 2.4% Megestrol 2.4% |
Bone-only 37.8% | CBR 41.5% mPFS 3.17 mo |
Neutropenia NR Anemia 2.8% Thrombocytopenia 8.3% Increased creatinine levels 2.8% |
Neutropenia G3 66.7% Febrile neutropenia 2.8% |
| Kish et al.32* | 763/64 | NA | NA | 1st: 39.5% 2nd: 15.7% 3th: 13.1% ≥4th: 31.7% |
LET 80.2% | NA | NA | Neutropenia 74.6% | Neutropenia 48.1% |
| Masuda et al.22§ | 42/62.5 | 100% | 0% | 1st: 100% | LET 100% | Visceral 47.6% Nonvisceral 52.4% Bone-only 14.3% |
1-year PFS 75% 1-year OS 92.9% mPFS and mOS NR ORR 40.5% Disease control 85.7% |
Neutropenia 100% Leukopenia 71.4% Thrombocytopenia 26.2% Anemia 19% Stomatitis 73.8% Infections 23.8% Constipation 21.4% Rash 19% ALT/AST increase 19%/16.7% |
Neutropenia 90.5% Leukopenia 50% Thrombocytopenia 2.4% Anemia 4.8% ALT/AST increase 9.5%/2.4% |
| Maurer et al.30* | 34/59.2 | 100% | NA/82.3% | ≥4 | F500 23.5% TAM 3.0% AI 73.5% |
Visceral 73.5% Bone-only 14.7% Other 11.8% |
PR 9% SD 36.4% PD 52% CR 3% mPFS 3.1 mo mOS NR |
Fatigue 55.9% | Fatigue G3/4 11.8% Neutropenia 76.5% Febrile neutropenia 2.9% Thrombocytopenia 11.8% Anemia G3 2.9% |
| Pizzuti et al.37* | 423/60 | 79.7% | 16.8%/19.8% | 1st: 37.3% ≥2 (2–12): 62.7% |
NA | Visceral 56.7% Bone-only 18.9% |
ORR 31% CBR 52.7% CR 4.5% PR 26.5% SD 41.4% PD 27.6% mPFS 12 mo mOS 24 mo |
Neutropenia 74.2% Anemia 28.9% Thrombocytopenia 22% Fatigue 43.5% Nausea/vomiting 14.2% Mucositis 7.1% Hypertransaminasemia 9.9% |
Neutropenia 43.2% Anemia G3 2.4% Thrombocytopenia G3 2.8% Fatigue G3 2.1% Mucositis G3 0.2% Hypertransaminasemia 0.2% |
| Stearns et al.23§ | 334/61 | 100% | NA/36.1% | NA | LET 100% | Bone 78.1% Liver 35.9% |
NA | Neutropenia 66.5% Leukopenia 19.8% Anemia 16.8% Thrombocytopenia 18% Fatigue 38% Nausea 22.5% Stomatitis 15.9% Arthralgia 12.3% Infection 25.4% Decreased appetite 11.1% |
Neutropenia 54.5% Leukopenia 8.1% Anemia G3 3.9% Thrombocytopenia 3.6% Fatigue G3 4.2% Nausea G3 1.5% Arthralgia G3 0.6% Infection 3.3% Febrile neutropenia 2.1% Decreased appetite G3 0.6% |
| Watson et al.35* | 64/62.5 | 80% | NA | 1st: 56% | LET 62.5% F500 31% TAM 3% EXE 3% |
Bone 72% Liver 39% Lung 36% Brain 6% |
PR 17% SD 21% PD 33% mPFS 12 weeks |
Neutropenia 95% Fatigue 43% Gastrointestinal 26% Infection 25% Anemia 11% Thromboembolic events 11.5% |
Thromboembolic events G3 1.5% Febrile neutropenia 1.5% Thrombocytopenia G3 11% |
| Palumbo et al.29§ | 150/64 | 80% |
Cohort A: 0/12% Cohort B: 43%/15% |
1st: 26.6% 2nd: 28.6% 3rd: 17.3% ≥4th: 27.3% |
LET: 43.3% (Cohort A) F500: 56.6% (Cohort B) |
Visceral 46% (Cohort A) and 55% (Cohort B) Bone-only 17% (Cohort A) and 20% (Cohort B) |
Cohort A: PR 32%, CBR 52%, mPFS 6.3 mo Cohort B: PR 25%, CBR 60%, mPFS 5.5 mo |
Neutropenia 67% Anemia 52% Thrombocytopenia 34% |
Neutropenia 35% |
| Taylor-Stokes et al.31* | 652/65 | 87.4% | NA | 1st: 57.7% 2nd: 34.8% ≥3rd: 7.5% |
LET 55% F500 45% |
Visceral 46.4% Nonvisceral 53.6% Bone-only 46.4% |
LET group: PFS (12 mo=85%,24 mo=64%) OS (12 mo=95%,24 mo=90%) ORR 79.5% CBR 93.8% F500 group: PFS (12 mo=79.8%) OS (12 mo=87.9%) ORR 74% CBR 85.1% |
NR | NR |
| Battisti et al.26* | 118/59 | 82.2% | NA | ≥4th: 96.6% | AI 48.3% F500 47.5% TAM 4.2% |
Visceral 81.4% Bone-only 6.8% |
CBR 47.5% ORR 15.8% CR 1% PR 14.8% SD 31.7% PD 52.7% mPFS 4.5 mo mOS 15.8 mo |
Neutropenia 89.7% Anemia 66.9% Thrombocytopenia 50% Fatigue 53.4% Hypertransaminasemia 32.2% Diarrhea 7.6% Stomatitis 16.9% Skin rash 3.4% Nausea 19.5% |
Neutropenia 56.8% Anemia 4.2% Thrombocytopenia 9.3% Fatigue 1.7% Hypertransaminasemia 5.1% Diarrhea 0.8% Stomatitis 0.8% Nausea 1.7% Febrile neutropenia 5.1% |
| Clifton et al.39* | 605/57 | 100% | NA | 1st: 46.8% 2nd: 20.7% ≥3rd: 32.6% |
LET 58.2% F500 40% Other 1.8% |
NA | PFS 344 days OS 882 days Dose reduction <65 yrs 35%; ≥65 yrs 42.5% Dose delay <65 yrs 37.5%; ≥ 65 yrs 51.3% |
NA | Neutropenic fever 2.1% Infection requiring antibiotic 19.3% Hospitalization 10.4% |
| Xi j et al.40* | 200/59.4 | 100% | NA | 1st: 21% 2nd: 25% ≥3rd: 54% |
LET 73.5% F500 25% ANA 1% TAM 0.5% |
NA | PFS 1st line 20.7 m; 2nd line 12.8 mo; 3rd line 4.0 mo Dose reduction 29% |
Neutropenia 47% Mucositis 4% Fatigue 3.5% Abscess 2% Nausea/vomiting 2% Diarrhea 1.5% Rash 1.5% Hypertransaminasemia 1.5% Neuropathy 1.5% |
Neutropenia 41.5% Dose reductions 29% |
| Waller J et al.41* | 162/60 | 91% | NA | 1st: 65% 2nd: 31% ≥3rd: 4% |
LET 65% F500 35% |
Bone 79% Liver 19% Lung 22% Lymph nodes 21% Other 17% |
CR 6% PR 60% SD≥24 weeks 21% SD<24 weeks 3% PD 3% 6 mo PFS 95% 6 mo OS 98% Dose reduction 77% Dose delay 15% |
NA | NA |
| Varella L et al.42 | 411/53.5 | NA | NA | 1st: 35.8% 2nd: 26% 3rd: 12.9% ≥4th: 25.3% |
LET 54.9% F500 38.4% Other 6.6% |
Bone 52.8% Visceral 36.7% Lung 22% Lymph nodes 14.1% Other 4.6% |
PFS 8.9 mo in LET group PFS 10.3 mo in F500 group OS not reached in LET group OS 24.5 mo in F500 group |
Anemia Thrombocytopenia Pancytopenia Diarrhea Anorexia Dyspnea Mucositis Hypertransaminasemia Skin rash Nausea |
Neutropenia 57.7% |
*
indicates retrospective trials;
§
indicates prospective trials;
AEs, adverse events; AI, aromatase inhibitor; ANA, anastrozole; CBR, clinical benefit rate; CR, complete response; CTSQ, Cancer Therapy Satisfaction Questionnaire; ET, endocrine treatment; EVE, everolimus; F500, Fulvestrant 500 mg; LET, letrozole; mo, months; mOS, median overall survival; mPFS, median progression-free survival; NA, not available; NR, not reached; ORR, overall response rate; PD, progressive disease; PR, partial response; SD, stable disease; TAM, tamoxifen; yrs, years.