Is early inclusion of neratinib with HER blockers possible in the treatment of stage 4 HER2 positive cancer?

Zilola Avazovna Olimova Ilboza medical, Tashkent, Uzbekistan info_outline Zilola Avazovna Olimova

Authors Zilola Avazovna Olimova Ilboza medical, Tashkent, Uzbekistan info_outline Zilola Avazovna Olimova Organizations Ilboza medical, Tashkent, Uzbekistan Abstract Disclosures Research Funding No funding sources reported Background: The management of the patients with breast cancer and choosing the most effective therapy still remains a challenge, but an achievable goal. 30-50% of the patients with stage IV HER2-positive breast cancer have an increased risk of developing brain metastases. In most patients, effective therapy for Her2+ BC does not reach the CNS due to the blood-brain barrier, which, in turn, can lead to cancer metastasis to the brain. Trastuzumab, Pertuzumab poorly penetrates the BBB, however the treatment regimens with the inclusion of trastuzumab increase life expectancy in patients with HER2+ BC with CNS metastases, mainly due to controlling of extracranial lesions. In contrast, neratinib penetrates the BBB well, and its combination with capecitabine produces responses in intensively pretreated patients, especially in cases where the only site of disease progression is the CNS. Our study was to directly compare the efficacy and safety of Neratinib plus Trastuzumab and Docetaxel(N+TDtx) and Pertuzumab plus Trastuzumab. Methods: This study involved 43 patients, among which 28 received (N+TDtx) -1 st group and 15 received (N+TDtx) - 2 nd group. A median number of 6 cycles were delivered in the two treatment arms, followed by Trastuzumab. Results: The primary endpoint was RFS and EFS. The median RFS was not reached in 2 nd group at a median follow-up of 18.7 months, because of brain metastasis, disease progression and death of 23 (82%) patients. However, the 12-month RFS rate was significantly higher in the 1 st group than in the 2nd 98% and 65%, respectively (hazard ratio [HR], 0.72; 95% CI, 0.56-0.93; P =.012). With median follow up of 36.4 months, neoadjuvant N+TDtx reduced the risk of disease recurrence, brain metastasis, progression or death by 98%, demonstrating a landmark three-year event-free survival (EFS) rate of 57% with N+TDtx, followed by trastuzumab compared to 17% with TDtx, followed by trastuzumab (Hazard Ratio [HR], 0.68; 95% Confidence Interval [CI], 0.49 to 0.93). The most frequent adverse event in the Neratinib arm was diarrhea, which was manageable with prophylactic treatment with loperamide. Conclusions: Neratinib, has shown that it was able to prevent brain metastases and demonstrated benefit in recurrence - free survival and event-survival in combination with Trastuzumab and Docetaxel over (PT+Dtx) for patients without brain metastases.