Brigatinib/carboplatin/lorlatinib

Abstract

Intractable nausea, hand swelling and drug resistance: case report In a case series of two patients, an approximately 60-year-old woman was described, who developed intractable nausea during treatment with brigatinib and carboplatin for ALK-rearranged adenocarcinoma of lungs. Additionally, she also developed drug resistance and hand swelling during treatment with lorlatinib for ALK-rearranged adenocarcinoma of lungs [routes, dosages, durations of treatments to reactions onsets not stated; not all outcomes stated]. The woman (Patient B) who was ex-smoker, was diagnosed ALK-rearranged adenocarcinoma of lungs at the age of 56 years. She was initially treated with neoadjuvant cisplatin and pemetrexed, surgical resection and postoperative radiation for stage IIIA lung cancer. The surgical specimen was positive for an ALK rearrangement adenocarcinoma of lungs. Unfortunately, 8 months later, symptomatic brain metastases developed that was treated with crizotinib, resection and stereotactic radiosurgery. More than 2 years of disease control was achieved with crizotinib therapy, followed by nearly 2 years of treatment with alectinib before duralbased metastases developed. Thus, brigatinib therapy was initiated; however, enlarging brain metastases developed after 2 months. Carboplatin, pemetrexed and bevacizumab were then added to the brigatinib regimen. However, she developed intractable nausea secondary to brigatinib and carboplatin. The woman’s brigatinib and carboplatin were discontinued after three cycles. After two additional cycles of bevacizumab and pemetrexed without brigatinib, a brain MRI established a new leptomeningeal enhancement in the setting of ongoing intolerable headaches. Molecular profiling revealed EML4-ALK fusion and six somatic mutations were also detected. Then, treatment with lorlatinib was initiated that resulted in almost immediate improvement in headaches and nausea. But, she developed mild hand swelling as an adverse effect from lorlatinib. After 3 months, asymptomatic brain metastases increased by 25%, suggesting rapid lorlatinib resistance. As a result, bevacizumab was then added to her lorlatinib regimen. The combination of lorlatinib and bevacizumab re-established disease control. There was no recurrence of previously debilitating headaches or nausea. Disease control with the combination lasted for 5.4 months. Thereafter, intracranial and extracranial progression (new hepatic metastasis) was noted. She discontinued treatment with bevacizumab and started gemcitabine therapy, in addition to lorlatinib.