abstract
OBJECTIVE:
In platinum-resistant ovarian
cancer,
adding pertuzumab to gemcitabine improved progression-free
survival in the subgroup with low tumor HER3 messenger RNA expression.
The 2-part PENELOPE trial (
NCT01684878) is prospectively investigating pertuzumab plus chemotherapy in this population.
PATIENTS AND METHODS:
Part
1 evaluated pertuzumab plus either topotecan or paclitaxel. Patients
with platinum-refractory or platinum-resistant recurrent ovarian,
primary peritoneal, or fallopian tube cancer and low HER3 messenger RNA
expression (concentration ratio ≤2.81 by central quantitative reverse
transcriptase-polymerase chain reaction testing on Cobas z480) received
intravenous pertuzumab (840 mg loading dose then 420 mg every 3 weeks)
with the investigator's choice of topotecan (1.25 mg/m days 1-5 every 3
weeks) or weekly paclitaxel (80 mg/m) until disease progression or
unacceptable toxicity. The primary objective was to assess safety and
tolerability.
RESULTS:
Fifty
patients were treated in part 1 (22 topotecan; 28 paclitaxel).
In both
cohorts, disease progression was the most common primary reason for
discontinuing pertuzumab, and the most common all-grade adverse events
(AEs) were fatigue/asthenia, anemia, and diarrhea. The most common
grade
≥3 AEs were anemia (36%), neutropenia (27%), and fatigue/asthenia (18%)
for topotecan, and peripheral sensory neuropathy (14%) and anemia (11%)
for paclitaxel. Two patients receiving paclitaxel-pertuzumab died from
AEs (abdominal infection; unexplained death). Median progression-free
survival was 4.1 months (95% confidence interval, 1.9-6.1) with
topotecan-pertuzumab and 4.2 months (95% confidence interval, 3.5-6.0)
with paclitaxel-pertuzumab.
CONCLUSIONS:
Based
on part 1 tolerability, the Independent Data Monitoring Committee
had
no objection to PENELOPE proceeding to part 2, a double-blind randomized
comparison of chemotherapy (topotecan, paclitaxel, or gemcitabine) plus
pertuzumab or placebo.
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