Spectrum Pharmaceutecals Inc (SPPI)

[AVII77]

Metastatic Breast Cancer Patient With Activating HER2 Exon 20 Insertion Mutation With Response to Poziotinib: Case Report of Compassionate Drug Use

https://www.clinical-breast-cancer.com/article/S1526-8209(18)30317-3/fulltext

In February 2017, the patient’s disease had progressed with worsening lymphangitic spread, increasing dyspnea, and increasing size of liver metastases. Gemcitabine therapy was initiated in February 2017, but by May 2017 the patient developed severe dyspnea and high tumor burden in her liver and lungs on imaging (Figure 1).

In June 2017, the US Food and Drug Administration granted approval for compassionate use of poziotinib. The typical starting dosage of poziotinib is 16 mg orally daily; however, because of grade 3 diarrhea and skin rash, as well as dose-limiting toxicities, the dose was lowered to 8 to 12 mg daily from June 2017 to October 2017. Her liver lesions resolved on computed tomography as of August 2017 (Figure 2), and CA27.29 dropped from over 400 U/mL in May 2017 to 27 in September 2017 (Figure 3). By September 2017 the patient had discontinued supplemental oxygen, and her exercise tolerance had markedly improved.

This was a heavily pre-treated patient. She ultimately died, but the figures show a complete response in the liver mets and it would appear her quality of life improved a bit (discontinued O2 and increased excercise tolerance).

She was treated with neoadjuvant paclitaxel for 3 weeks, which
was discontinued because of poor tolerability

she received neoadjuvant doxorubicinecyclophosphamide for 2 cycles, which was again discontinued because of poor tolerability

She underwent right modified radical mastectomy in August 2011, which found a 4.0 cm residual tumor with 7 of 25 axillary lymph nodes positive for tumor

She declined adjuvant chest wall radiation and was placed on 1 year of adjuvant trastuzumab treatment as well as a planned 5 years of letrozole.

She was treated with a variety of sequential single-agent therapies over the next 18 to 24 months, including fulvestrant, tamoxifen, and exemestane; trastuzumab/pertuzumab and trastuzumabeemtansine (using her primary tumor as a rationale for HER2-based therapy); and capecitabine. All of these therapies resulted in brief periods of stability (3-6 months), followed by slow progression of computed tomography imaging (with bilateral interstitial lung disease consistent with lymphangitic spread) and gradual increase in dyspnea, increasing fatigue, and decreasing exercise tolerance.

In May 2015, lapatinib was provided for 2 months with stable disease on imaging but was discontinued as a result of severe diarrhea despite antidiarrheals and dose reduction. This was followed by nab-paclitaxel for 6 months, then eribulin for 6 months, with stability followed by slow progression of lymphangitic spread and continued dyspnea.

In August 2016, neratinib was obtained for compassionate use after US Food and Drug Administration approval, and with aggressive diarrhea prophylaxis, this agent was tolerated with a 25% dose reduction. This resulted in stabilization of her disease and improved dyspnea, with decreasing requirements for supplemental oxygen and increased exercise tolerance.