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Association details:
Evidence:
Evidence Level:
Sensitive: A2 - Guideline
New
Source:
Excerpt:
Three different regimens are recommended by the panel as options for subsequent treatment of mCRC with HER2 amplifications: fam-trastuzumab deruxtecan-nxki (T-DXd) monotherpay or trastuzumab in combination with either pertuzumab or lapatinib.
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

DETERMINE Trial Treatment Arm 04: Trastuzumab in Combination With Pertuzumab in Adult, Teenage/Young Adult and Paediatric Patients With Cancers With HER2 Amplification or Activating Mutations

Excerpt:
...Confirmed diagnosis of a malignancy harbouring HER2 amplification, or an appropriate activating mutation as defined by the MTB, using an analytically validated method....
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Pertuzumab Plus Trastuzumab for Treatment-Refractory HER2-Amplified Metastatic Colorectal Cancer: Comparison of the MyPathway Trial With a Real-World External Control Arm

Published date:
06/01/2022
Excerpt:
A noninterventional study was conducted using patient-level data from MyPathway participants receiving PER-HER and real-world patients with HER2-amplified...The estimated HR for OS from the multivariate Cox proportional hazards model in the postweighting population was 0.729 (95% CI, 0.184 to 3.900). The results of sensitivity analyses were consistent with the primary analysis in terms of the point estimate of HR.
DOI:
10.1200/CCI.22.00022
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Comparative analysis of overall survival in patients with HER2-amplified treatment-refractory metastatic colorectal cancer treated with pertuzumab plus trastuzumab in Mypathway and patients treated in the real-world.

Published date:
01/18/2022
Excerpt:
In MyPathway, patients with treatment-refractory HER2-amplified metastatic colorectal cancer (mCRC) were enrolled and received pertuzumab plus trastuzumab….In the post-weighting population, the hazard ratio (HR) for OS estimated by multivariate Cox regression model was 0.729 (95% CI: 0.184-3.900) and median survival in the PER/HER arm and the EC arm were 11.47 months (95% CI: 7.72-22.11) and 9.72 months (95% CI: 7.43-22.21), respectively....Despite a small sample size, the totality of findings suggests that the combination of pertuzumab and trastuzumab could have a potential benefit in OS for this population.
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial

Published date:
11/11/2021
Excerpt:
HER2 amplification was confirmed in tissue and/or ctDNA in 30 patients with mCRC. The study met the primary endpoint with a confirmed objective response rate of 30% in 27 tissue-positive patients and 28% in 25 ctDNA-positive patients, as compared to an objective response rate of 0% in a matched real-world reference population treated with standard-of-care salvage therapy....Pertuzumab plus trastuzumab showed similar efficacy in patients with mCRC with HER2 amplification in tissue or ctDNA, showing that ctDNA genotyping can identify patients who benefit from dual-HER2 blockade as well as monitor treatment response.
DOI:
https://doi.org/10.1038/s41591-021-01553-w
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Pertuzumab plus trastuzumab and real-world standard of care (SOC) for patients (pts) with treatment refractory metastatic colorectal cancer (mCRC) with HER2 (ERBB2) amplification (amp) confirmed by tumor tissue or ctDNA analysis (TRIUMPH, EPOC1602).

Published date:
05/19/2021
Excerpt:
Among 75 pts screened, concordance of HER2 amp between tissue and ctDNA was 83%....The primary endpoint was met in each cohort of TRIUMPH, with confirmed ORR of 30% (95% CI 14-50%) in 27 tissue+ pts and 28% (12-49%) in 25 ctDNA+ pts....We demonstrate promising efficacy and safety of P+T for...mCRC pts with HER2 amp in either tumor tissue or ctDNA.
DOI:
10.1200/JCO.2021.39.15_suppl.3555
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

553P - Activity of trastuzumab and pertuzumab (HP) in patients with non-breast/gastroesophgeal HER2-amplified tumours: Results of the NCI-MATCH trial (EAY131) subprotocol J

Published date:
09/14/2020
Excerpt:
NON-SUPPORTIVE EVIDENCE: The confirmed ORR was 8.3% (2/24 partial responses [colorectal and cholangiocarcinoma], 90% CI 1.5-24%). There was one additional unconfirmed partial response (PR, urothelial cancer). Median PFS was 3.3 months (90% CI 2.0 - 4.6), 6-month PFS 23.3% (90% CI 13.6 – 40.1) and median OS 8.1 months (90% CI 5.5 - 12.4). Treatment-emergent adverse events were consistent with prior HP studies. There was no association between HER2 CN and response....HP had activity in a minority of tumours in this population, but did not meet the predefined efficacy benchmark for non-breast/gastroesophageal cancers with HER2 amplifications by NGS.
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
New
Title:

Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study

Excerpt:
Thirty of 114 patients (26%; 95% CI, 19% to 35%) with HER2 amplification/overexpression had objective responses to treatment with trastuzumab plus pertuzumab (two CR, 28 PR). Objective responses were seen in nine primary tumor types: colorectal, bladder, biliary, salivary gland, NSCLC, pancreas, ovary, prostate, and skin (apocrine; Table 3).
DOI:
10.1200/JCO.2017.75.3780
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
New
Title:

Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study

Excerpt:
Patients in this subset analysis were aged 18 years or older and had treatment-refractory, histologically confirmed HER2-amplified metastatic colorectal cancer...Patients received pertuzumab (840 mg loading dose, then 420 mg every 3 weeks, intravenously) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks, intravenously)...Among these 57 evaluable patients, as of Aug 1, 2017, one (2%) patient had a complete response and 17 (30%) had partial responses; thus overall 18 of 57 patients achieved an objective response (32%, 95% CI 20-45).
DOI:
10.1016/S1470-2045(18)30904-5
Trial ID:
Evidence Level:
Sensitive: D – Preclinical
Title:

Sensitivity of HER2-amplified colorectal organotypic cancer spheroids at ex vivo resistance to panitumumab and trastuzumab

Published date:
01/11/2021
Excerpt:
Normalized NADH/FAD ratio revealed significant metabolic response to panitumumab (-20%, G?=0.66) and trastuzumab/pertuzumab (-35%, G?=1.16) with insignificant effect of single agent trastuzumab (-14%, G?=0.46). Therapeutic dose escalation in a single PDCO of HER2 amplified CRC suggests improved sensitivity to EGFRi and dual HER2 targeting with trastuzumab/pertuzumab.