You are here
Adverse events with pertuzumab and trastuzumab: Evolution during treatment with and without docetaxel in CLEOPATRA.
J Clin Oncol 30, 2012 (suppl; abstr 597^)
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: In CLEOPATRA, the HER2-dimerization inhibitor pertuzumab (P) was combined with trastuzumab (T) and docetaxel (D) in HER2-positive 1st-line MBC. P+T+D significantly improved efficacy compared with placebo (Pla)+T+D while having little effect on safety. Pts were recommended to receive ≥6 cycles of D but could discontinue D prior to Cycle 6 due to poor tolerability or progressive disease (PD) or continue D beyond Cycle 6 at investigators’ discretion. Once D was discontinued, pts received Pla+T or P+T until PD. To understand the full safety profile of the regimen, adverse events (AEs) occurring before and after D discontinuation were analyzed. Methods: Treatment was given q3w (Pla/P: 840 mg loading, then 420 mg; T: 8 mg/kg loading, then 6 mg/kg; D: 75 mg/m2, escalating to 100 mg/m2 if tolerated; de-escalation by 25% allowed). AEs were graded according to NCI-CTCAE v3.0, monitored continuously during the treatment period, and their relationship to study drugs was assessed by investigators. Results: From 808 pts enrolled, 804 were analyzed in the safety population (pts who received ≥1 dose of study treatment). AEs that led to discontinuation of all study treatment were experienced by 5.3% (Pla+T+D) and 6.1% (P+T+D) of pts, whereas discontinuation of D alone due to AEs occurred in 23.2% (Pla+T+D) and 23.6% (P+T+D) of pts. Conclusions: Treatment in both arms was well tolerated. After discontinuation of D, there was a clear reduction in grade ≥3 AEs; however, the incidence of grade ≥3 diarrhea remained slightly elevated with P+T+D. The AE profile of P+T is consistent with that seen in previous Phase II studies (Gianni Lancet Oncol 2012; Baselga JCO 2010). These data suggest that the combination of P+T may also be well tolerated in other breast cancer settings, such as in adjuvant therapy, which is currently under phase III study (APHINITY; NCT01358877).
|AE, n (%)||Incidence during
all study treatment
|Pla+T+D (n=397)||P+T+D (n=407)||Pla+T (n=255)||P+T (n=298)|
|Neutropenia||182 (45.8)||199 (48.9)||4 (1.6)||0 (0.0)|
|Febrile neutropenia||30 (7.6)||56 (13.8)||0 (0.0)||0 (0.0)|
|Leukopenia||58 (14.6)||50 (12.3)||1 (0.4)||0 (0.0)|
|Diarrhea||20 (5.0)||32 (7.9)||0 (0.0)||3 (1.0)|
Abstracts by José Baselga:
A phase 1 dose-escalation study of anti-HER3 monoclonal antibody LJM716 in combination with trastuzumab in patients with HER2-overexpressing metastatic breast or gastric cancer.
A phase 1 study of LJM716 in patients with esophageal squamous cell carcinoma, head and neck cancer, or HER2-overexpressing metastatic breast or gastric cancer.
A virtual consult service to optimize clinical trial participation in patients with metastatic breast cancer.
Presentations by José Baselga:
A first-in-human Phase I study of BKM120, an oral pan-class I PI3K inhibitor, in patients with advanced solid tumorsSession: Paths for Clinical Development of PI3K Inhibition (Clinical Science Symposium)
Meeting: 2009 ASCO Annual Meeting
Session: ASCO/ESMO Symposium: Global Clinical Trials - Challenges and Solutions (Special Session)