Time to first tumor progression as outcome predictor of a second trasuzumab-based therapy beyond progression in HER-2 positive metastatic breast cancer.
In a previous analysis performed on a cohort of 37 HER-2 positive metastatic breast cancer (MBC) patients treated with trastuzumab beyond progression, we found that a second trastuzumab-based therapy is associated with a considerable response rate and preserved time to progression as compared with a first trastuzumab-based therapy. In the present study, we extended the analysis to a total of 69 patients treated in four different italian Institutions, also trying to identify clinical predictors of sensitivity to a second trastuzumab-based therapy beyond progression. Efficacy results on the overall population confirmed that a second trastuzumab-based therapy beyond progression is an active regimen (27.5% of responses and 6.5 months of time to progression, respectively). Median time to progression to the first trastuzumab therapy (TTP1) identified two groups of patients with different sensitivity to trastuzumab beyond progression (group A, TTP1 >or= 8 months and group B, TTP1 < 8 months) in terms of time to second progression and post-progression survival (group A versus group B showed respectively a time to second progression of 7.6 versus 4.7 months, p = 0.05, and a post-progression survival of 31.7 months versus 21.8 months, p = 0.04). In the multivariate analysis, only TTP1 was a predictor of time to second progression and post-progression survival. Despite the recent approval of lapatinib plus capecitabine for trastuzumab-progressing patients, it is still reasonable to offer trastuzumab beyond progression to HER-2 positive MBC patients, because these data confirm the potential utility of such a conduct. In the clinic, time to first tumor progression may represent a useful tool to identify patients who are more likely to benefit from trastuzumab beyond progression.
Metro
Giulio
G
Division of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy.
Giannarelli
Diana
D
Gemma
Donatello
D
Lanzetta
Gaetano
G
Ciccarese
Mariangela
M
Papaldo
Paola
P
Gamucci
Teresa
T
Lorusso
Vito
V
Mottolese
Marcella
M
Magnolfi
Emanuela
E
Cognetti
Francesco
F
Fabi
Alessandra
A
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000556:secondary; D015331:Cohort Studies; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011336:Probability; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012074:Remission Induction; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013997:Time Factors; D000068878:Trastuzumab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab