Abstract
Background
Dual-HER2 targeted therapy has led to a promising antitumor effect in HER2 positive
cancers including gastrointestinal cancer. The present data focus on patients with
HER2 positive colorectal cancer who received pyrotinib and trastuzumab after failure
to standard second-line treatment.
Methods
Patients diagnosed of HER2 positive refractory or metastatic colorectal cancer were
enrolled to receive trastuzumab in combination with pyrotinib as third-line and beyond
therapy. Trastuzumab was given as a loading dose at 8 mg/kg followed by 6mg/kg once
every 3 weeks, and oral pyrotinib as 400 mg per day until progression. ORR was set
as the primary endpoint. PFS and OS were set as a secondary endpoints. This trial
is registered with Clinical Trial.gov, NCT04960943, and is ongoing.
Results
Between February 2020 to December 2021, 16 patients including 14 with RAS wild-type
status were enrolled in this cohort. ORR was 50.0% in the overall population, and
57.1% in RAS wild-type patients. At a median follow-up of 11.2 months, median PFS
and OS were 7.53 and 16.8 months, respectively. The RAS/BRAF wild-type patients had
prolonged survival (PFS: 7.53 vs. 1.63 months, P = .02; OS: NR vs.4.13 months, P = .001) compared with RAS/BRAF mutant patients. The most common treatment-emergent
adverse event (TEAE) reported is diarrhea. Five (31.3%) patients reported grade 3
TEAEs, and no death was reported.
Conclusions
Trastuzumab in combination with pyrotinib demonstrated encouraging antitumor activity
that translated to prolonged survival benefit in HER2 positive refractory or mCRC
patients who are RAS wild-type with acceptable tolerance.
Keywords
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Article info
Publication history
Published online: July 15, 2022
Accepted:
July 11,
2022
Received in revised form:
June 29,
2022
Received:
May 16,
2022
Identification
Copyright
© 2022 Published by Elsevier Inc.
