TABLE II.
Summary of Results for Older versus Younger Patients
| Parameter | Older patients (≥65 y) (n = 64) | Younger patients (<65 y) (n = 224) |
|---|---|---|
| Median (range) age, y | 70 (65–91) | 48 (18–64) |
| ECOG performance status,a n (%) | ||
| 0 | 39 (61) | 181 (81) |
| 1 | 25 (39) | 41 (18) |
| 2 | 0 | 1 (<1) |
| Median (range) time since CML diagnosis, y | 5.5 (0.1–13.7) | 3.2 (0.1–15.1) |
| Key baseline medical conditions, n (%) | ||
| Gastrointestinal disorders | 38 (59) | 77 (34) |
| Vascular disorders | 31 (48) | 52 (23) |
| Metabolism disorders | 27 (42) | 70 (31) |
| Diabetes mellitus | 2 (3) | 7 (3) |
| Musculoskeletal disorders | 27 (42) | 60 (27) |
| Blood/lymphatic disorders | 26 (41) | 67 (30) |
| Cardiac disordersb | 25 (39) | 23 (10) |
| Nervous system disorders | 23 (36) | 31 (14) |
| Respiratory disorders | 19 (30) | 31 (14) |
| Endocrine disorders | 11 (17) | 16 (7) |
| Hepatobiliary disorders | 4 (6) | 19 (9) |
| Median (range) no. of baseline medications | 4 (1–14) | 2 (1–16) |
| Median (range) duration of bosutinib, mo | 13.8 (0.3–48.9) | 22.1 (0.2–60.8) |
| Median (range) follow-up, mo | 33.8 (1.0–53.0) | 31.7 (0.6–66.0) |
| Cytogenetic response,c n (%) [95% CI] | ||
| Evaluable patients | 62 | 204 |
| MCyR | 33 (53) [40–66] | 124 (61) [54–68] |
| CCyR | 29 (47) [34–60] | 99 (49) [42–56] |
| Probability of retaining MCyR at 2 yearsd | 72% [52–85] | 78% [69–84] |
| Hematologic response,e n (%) [95% CI] | ||
| Evaluable patients | 64 | 223 |
| CHR | 52 (81) [70–90] | 192 (86) [81–90] |
| Probability of retaining CHR at 2 yearsd | 65% [48–77] | 74% [67–80] |
| Non-hematologic TEAEs with ≥8% difference between age groups | ||
| Vomiting | 29 (45) | 77 (34) |
| Fatigue | 23 (36) | 44 (20) |
| Decreased appetite | 17 (27) | 23 (10) |
| Weight decreased | 14 (22) | 9 (4) |
| Asthenia | 13 (20) | 23 (10) |
| Nasopharyngitis | 12 (19) | 24 (11) |
| Dyspnea | 12 (19) | 13 (6) |
| Peripheral edema | 10 (16) | 13 (6) |
| Increased ALT | 9 (14) | 53 (24) |
| Pleural effusion | 9 (14) | 6 (3) |
| Increased AST | 8 (13) | 46 (21) |
| Increased lipase | 8 (13) | 11 (5) |
| Chills | 8 (13) | 8 (4) |
| Increased blood creatinine | 8 (13) | 5 (2) |
| Abdominal pain | 7 (11) | 60 (27) |
| Influenza | 1 (2) | 22 (10) |
| Dose interruption due to a TEAE, n (%) | 49 (77) | 153 (68) |
| Dose reduction due to a TEAE, n (%) | 36 (56) | 101 (45) |
| Discontinuation due to an AE, n (%) | 19 (30) | 47 (21) |
| Death within 30 days of last dose due to an AE, n (%) | 1 (2) | 2 (1) |
| Transformation to AP/BP CML, n | 2 | 9 |
| PFS at 2 yearsd [95% CI] | 76% [60–87] | 82% [75–87] |
| OS at 2 yearsd [95% CI] | 87% [75–93] | 92% [87–95] |
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AP, accelerated phase; AST, aspartate aminotransferase; BP, blast phase; CCyR, complete cytogenetic response; CHR, complete hematologic response; CML, chronic myeloid leukemia; ECOG, Eastern Cooperative Oncology Group; FISH, fluorescence in situ hybridization; MCyR, major cytogenetic response; OS, overall survival; PCyR, partial cytogenetic response; PFS, progression-free survival; Ph+, Philadelphia chromosome-positive; TEAE, treatment-emergent adverse event.
ECOG Performance Status was missing for 1 younger, imatinib-intolerant patient.
The most common cardiac events at baseline (≥3 patients) were coronary artery disease (older, n = 6; younger, n = 1), myocardial infarction (n = 5; n = 1, respectively), acute myocardial infarction (n = 2; n = 3), arrhythmia (n = 3; n = 2), cardiomyopathy (n = 3; n = 2), and palpitations (n = 2; n = 2).
Evaluable patients must have had an adequate baseline cytogenetic assessment. Cytogenetic response [27] was determined using standard cytogenetics (G-band karyotype) with ≥20 metaphases counted for postbaseline assessments; if <20 metaphases were available post-baseline, FISH analysis of bone marrow aspirate with ≥200 cells for the presence of Bcr-Abl fusion gene was used. MCyR included PCyR (1–35% Ph+ metaphases) and CCyR (0% Ph+ metaphases; <1% if using FISH). Cytogenetic response could be achieved during the study or maintained from baseline for ≥4 weeks.
Probabilities at 2 years were based on Kaplan–Meier estimates.
Evaluable patients must have had an adequate baseline hematologic assessment. The definition of CHR was standard [22]; hematologic response was required to be confirmed and to last for ≥4 weeks, with peripheral blood and/or bone marrow documentation, and could be achieved during the study or maintained from baseline for ≥5 weeks.