ABSTRACT
BACKGROUND: Brigatinib is a potent ROS1 inhibitor. The existing data on its clinical activity in ROS1-rearranged non-small cell lung cancer (NSCLC) are limited to four cases. METHODS: Six patients with ROS1-rearranged advanced NSCLC treated with brigatinib were identified through search of the internal databases of four participating cancer centers. Four additional patients were selected by PubMed and Google Scholar search. The objective response rate (ORR), progression-free survival (PFS) (RECIST v.1.1), duration of treatment (DOT), and safety were assessed. RESULTS: Of eight patients evaluable for response assessment (crizotinib naive-1, crizotinib resistant -7), three patients demonstrated a partial response (ORR-37%). One crizotinib-naive patient had an ongoing response at 21.6 months. Of seven crizotinib-resistant patients, two patients demonstrated a partial response (ORR-29%), and one patient (14%) had stable disease. PFS, available in four crizotinib-resistant patients, was 7.6 + , 2.9, 2.0, and 0.4 months. In crizotinib-resistant patients, DOT was 9.7 + , 7.7 + , 7.6 + , 4.0, 2.0, 1.1, 0.4 months, and was not reported in two patients. Genomic profiling in one responder revealed no ROS1 alteration, suggesting that the response was attributable to "off-target" brigatinib activity. In two patients with progressive disease, genomic profiling demonstrated a cMET exon 14 mutation + KRAS G12A mutation in one case, and a persisting ROS1-CD74 fusion + TP53 K139N, FGFR2 E250G, ATM G2695D, and NF1 R2258Q mutations in the other. No grade 3-5 toxicity was observed. CONCLUSION: Brigatinib demonstrated modest activity in crizotinib-resistant ROS1-rearranged NSCLC. Its intracranial and systemic activity should be assessed in correlation with the underlying molecular mechanism of crizotinib resistance.
Our series is the first to describe brigatinib activity in ROS1-altered NSCLC. In crizotinib-resistant patients, ORR with brigatinib was 29%. PFS with brigatinib was 7.6+, 2.9, 2.0, and 0.4 months. DOT with brigatinib was 9.7+, 7.7+, 7.6+, 4.0, 2.0, 1.1, 0.4 months. The correlation between response and molecular resistance needs further exploration.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Crizotinib/therapeutic use , Lung Neoplasms/drug therapy , Organophosphorus Compounds/therapeutic use , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins/genetics , Pyrimidines/therapeutic use , Aged , Aged, 80 and over , Antigens, CD/genetics , Cancer Care Facilities , Carcinoma, Non-Small-Cell Lung/genetics , Drug Resistance, Neoplasm , Female , Gene Rearrangement/genetics , Genes, ras/genetics , Humans , Lung Neoplasms/genetics , Male , Middle Aged , Mutation , Oncogene Proteins, Fusion , Organophosphorus Compounds/adverse effects , Progression-Free Survival , Protein-Tyrosine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins/antagonists & inhibitors , Proto-Oncogene Proteins c-met/genetics , Pyrimidines/adverse effects , Sialyltransferases/geneticsABSTRACT
BACKGROUND: Limited research is available on the perspectives of patients with cancer regarding integration of complementary medicine (CM) in conventional supportive cancer care. The purpose of this study was to explore patients' perspectives concerning CM integration within conventional oncology settings. PATIENTS AND METHODS: A 27-item questionnaire was constructed and administered to a convenient sample of Arab patients receiving cancer care in three oncology centers in northern Israel. RESULTS: Of the 324 respondents (94.7% response rate), 124 of 313 (39.6%) reported the use of CM for cancer-related outcomes. A logistic regression model indicated that CM was used with active chemo- or radiotherapy treatment [EXP [B], 2.926, 95% confidence interval (CI) 1.276-6.708; P=0.011] and a higher degree of spiritual quest (EXP [B], 3.425, 95% CI 1.042-11.253; P=0.043). Herbal medicine was the leading CM modality (87.9% of CM users), which included the use of 28 plants and traditional remedies, of which 17 were used to improve QOL, with 5 of the herbs having potential interactions with chemotherapy. 83.1% of respondents stated that they would consult with a CM provider if CM were to be integrated into the oncology department. Patients' expectation of CM consultation was clearly associated with expectations of QOL improvement, coping with cancer, and alleviating chemotherapy's side-effects when compared with expectations of cancer cure (P<0.0001). The three leading concerns which patients expected to be improved by integrative CM treatment were gastrointestinal symptoms (63.2%), fatigue (51.9%), and pain (40.5%). CONCLUSIONS: Integrative CM consultations should focus on the improvement of QOL concomitant with safety concerns regarding potential drug-herb interactions. The need to integrate a nonjudgmental yet evidence-based CM consultation service may also be applicable to oncology institutions challenged with culturally diverse populations with a high prevalence of traditional medicine use.
