Discussion
Leukopenia, pneumonia, neutropenia, diarrhea, leukopenia, febrile neutropenia, anemia, hypertension
LEUKOPENIA, PNEUMONIA, NEUTROPENIA, LEUKOPENIA, FEBRILE NEUTROPENIA, DISEASE, ANEMIA, HYPERTENSION
PUFFIN previously met its primary objectives, demonstrating consistency of efficacy with CLEOPATRA [Subgroup analyses showed consistency with the overall PFS and OS results. Compared with the primary PFS subgroup analysis, the final analysis showed an overall shift toward the pertuzumab group having improved PFS and OS, with little difference between disease type, hormone receptor status, and low or high HER2 status. Patients aged ≥ 65 years showed no difference in PFS between arms. Subgroup analyses showed that patients in the < 65 years age group [PFS HR = 0.58 (95% CI 0.43, 0.80) and OS HR = 0.60 (95% CI 0.39, 0.94)] had better outcomes with pertuzumab. Patients who were ≥ 2 years treatment-free had improved PFS over patients who were < 2 years treatment-free [HR = 0.43 (95% CI 0.25, 0.75) vs. HR = 0.67 (95% CI 0.36, 1.25)]. However, the OS subgroup analysis showed patients who were < 2 years treatment-free had improved OS over patients who were ≥ 2 years treatment-free [HR = 0.30 (95% CI 0.10, 0.92) vs. HR = 0.68 (95% CI 0.32, 1.46)]. Patients with de novo disease had poorer OS with pertuzumab compared with placebo [HR = 1.22 (95% CI 0.58, 2.59)]; this conflicts with CLEOPATRA [HR = 0.65 (95% CI 0.51, 0.82)], which showed that patients with no previous treatment had better prognosis with pertuzumab than with placebo [The overall safety profile was consistent with the primary analysis, with few AEs reported that required additional follow-up in either arm, and no new safety signals. Leukopenia remained the most common AE in the study, followed by neutropenia. Grade ≥ 3 AEs remained balanced between arms, with neutropenia, leukopenia, febrile neutropenia, anemia, and diarrhea being the most reported (with the addition of hypertension and pneumonia since the primary analysis). No new cardiac AEs were reported since the primary analysis. Comparing the safety profile to the Asian population in CLEOPATRA’s exploratory analysis, the rates of AEs of special interest to pertuzumab were lower, specifically diarrhea (45.9% vs. 74.4% vs.) and febrile neutropenia (4.1% vs. 25.6%) [