Trastuzumab resistance in breast cancer is an ongoing challenge
.

Recently, the European Journal of Cancer published a phase II study (RADHER), in patients with HER2-positive early operable breast cancer, the efficacy and predictive marker of the mTOR inhibitor everolimus added to trastuzumab before surgery Explore

Patients were randomized 1:1 to receive trastuzumab (initial dose 4mg/kg, then 2mg/kg weekly for 5 weeks) alone (T) or in combination with everolimus (10 mg/day for 6 weeks) ( T+E), and then proceed to surgery
.

At baseline and during treatment, the tumor is evaluated through clinical examination and ultrasound

Patients were randomized 1:1 to receive trastuzumab (initial dose 4mg/kg, then 2mg/kg weekly for 5 weeks) alone (T) or in combination with everolimus (10 mg/day for 6 weeks) ( T+E), and then proceed to surgery

From July 2008 to April 2012, 82 patients were enrolled, with 41 patients in each group

Clinical efficacy

Clinical efficacy

Adding everolimus can increase toxicity, especially mucositis (82.
5% vs.
5.
0%) and rash (57.
5% vs.
10.
0%), but grade III/IV events are rare
.

The grade III-IV AEs in the T+E group was 22.

Adding everolimus can increase toxicity, especially mucositis (82.

Ki-67 in the two groups was significantly reduced between baseline and surgery (P<0.

Marker analysis

Marker analysis

Considering the entire patient population, PIK3CA mutation (P=0.
991) and PTEN inhibition rate (P=0.
300) were not significantly changed between baseline and surgical specimens
.

PIK3CA mutation status is related to clinical response (P=0.

Considering the entire patient population, PIK3CA mutation (P=0.

In the T group, pMEK1 and pERK1/2 had no significant difference between baseline and surgery
.

In the T+E group, significant differences were observed between pMEK1 (P=0.

In the T group, pMEK1 and pERK1/2 had no significant difference between baseline and surgery

In summary, studies have shown that the addition of everolimus did not improve the efficacy, but induced the MAPK signaling pathway
.
In this case, consideration should be given to overcoming the crossover of pathways caused by combination therapy to maximize the effectiveness of trastuzumab
.
Studies have shown that the addition of everolimus did not improve the efficacy, but induced the MAPK signaling pathway
.
In this case, consideration should be given to overcoming the crossover of pathways caused by combination therapy to maximize the effectiveness of trastuzumab
.
Studies have shown that the addition of everolimus did not improve the efficacy, but induced the MAPK signaling pathway
.
In this case, consideration should be given to overcoming the crossover of pathways caused by combination therapy in order to maximize the effectiveness of trastuzumab
.

Original source:

Original source:

Campone M, Bachelot T, Treilleux I, Pistilli B, Salleron J, Seegers V, Arnedos M, Loussouarn D, Wang Q, Vanlemmens L, Jimenez M, Rios M, Diéras V, Leroux A, Paintaud G, Rezai K, André F , Lion M, Merlin JL.
A phase II randomised study of preoperative trastuzumab alone or combined with everolimus in patients with early HER2-positive breast cancer and predictive biomarkers (RADHER trial).
Eur J Cancer.
2021 Oct 19;158:169-180 .
doi: 10.
1016/j.
ejca.
2021.
09.
017.
Epub ahead of print.
PMID: 34678678.

Campone M, Bachelot T, Treilleux I, Pistilli B, Salleron J, Seegers V, Arnedos M, Loussouarn D, Wang Q, Vanlemmens L, Jimenez M, Rios M, Diéras V, Leroux A, Paintaud G, Rezai K, André F , Lion M, Merlin JL.
A phase II randomised study of preoperative trastuzumab alone or combined with everolimus in patients with early HER2-positive breast cancer and predictive biomarkers (RADHER trial).
Eur J Cancer.
2021 Oct 19;158:169-180 .
doi: 10.
1016/j.
ejca.
2021.
09.
017.
Epub ahead of print.
PMID: 34678678.
Leave a message here