Pralsetinib in patients with RET fusion-positive non-small-cell lung cancer: A plain language summary of the ARROW study.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a research study called ARROW, which tested a medicine called pralsetinib in patients with non-small cell lung cancer (NSCLC), thyroid cancer, and other advanced solid tumours caused by a change in a gene called RET. For the purposes of this summary, only patients with NSCLC with a change in RET called fusion (RET fusion+) are highlighted. WHAT WERE THE RESULTS?: In total, 281 patients with RET fusion+ NSCLC had taken part in this study across the USA, Europe, and Asia. Patients were asked to take four pills (adding up to 400 mg) of pralsetinib each day and were checked for any changes in their tumours, as well as for any side effects. After an average of 8 months of treatment with pralsetinib, 72% of previously untreated patients and 59% of patients who had previously received chemotherapy had considerable shrinkage of their tumours. Among 10 patients with tumours which had spread to the brain (all of whom had received previous treatments), 70% had their tumours shrink greatly in the brain after treatment with pralsetinib. On average, patients lived with little to no tumour growth for 16 months. In previously untreated patients, the most common severe side effects that were considered related to pralsetinib treatment were decreased white blood cells (neutrophils and lymphocytes), increased blood pressure, and an increase in a blood protein called creatine phosphokinase. In previously treated patients, the severe side effects were decreased white blood cells (neutrophils, lymphocytes, and leukocytes), increased blood pressure, and low levels of red blood cells. In both untreated and previously treated patients, the most common severe side effects that required hospital attention were lung inflammation/swelling causing shortness of breath (pneumonitis) and lung infection (pneumonia). WHAT DO THE RESULTS MEAN?: Overall, the ARROW study showed that pralsetinib was effective in shrinking tumours in patients with RET fusion+ NSCLC regardless of previous treatment history. The recorded side effects were expected in patients receiving this type of medicine. Clinical Trial Registration: NCT03037385 (ARROW) (ClinicalTrials.gov).

Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis.

Advanced systemic mastocytosis (AdvSM) is a rare myeloid neoplasm associated with poor overall survival (OS). This study (NCT04695431) compared clinical outcomes between patients with AdvSM treated with avapritinib in the Phase 1 EXPLORER (NCT0256198) and Phase 2 PATHFINDER (NCT03580655) trials (N = 176) and patients treated with best available therapy (BAT; N = 141). A multi-center, observational, retrospective chart review study was conducted at six study sites (four European, two American) to collect data from patients with AdvSM who received BAT; these data were pooled with data from EXPLORER and PATHFINDER. Comparisons between outcomes of OS, duration of treatment (DOT), and maximum reduction in serum tryptase were conducted between the treatment cohorts, with adjustment for key covariates. The results indicated that the avapritinib cohort had significantly better survival (adjusted hazard ratio (HR) (95% confidence interval (CI)): 0.48 (0.29, 0.79); p = 0.004) and significantly longer DOT (HR: 0.36 (0.26, 0.51); p < 0.001) compared to the BAT cohort. Additionally, the mean difference in percentage maximum reduction in serum tryptase levels was 60.3% greater in the avapritinib cohort (95% CI: -72.8, -47.9; p < 0.001). With no randomized controlled trials comparing avapritinib to BAT, these data offer crucial insights into the improved efficacy of avapritinib for the treatment of AdvSM.

Risk factors for progression or death after first-line platinum-based chemotherapy in real-world patients in the USA with ovarian cancer from 2011 to 2018.

Aim: Patient chart data from the USA during the period of January 2011 through October 2018 were used to assess risk factors for progression in advanced ovarian cancer after response to first-line platinum-based chemotherapy. Patients & methods: Patients with stage III/IV ovarian cancer who completed first-line platinum-based chemotherapy after primary or interval debulking surgery were identified from the Flatiron Health database. Cox proportional hazards modeling was used to assess associations between baseline factors and time to next treatment (TTNT) or overall survival (OS). Results: Patients at stage IV or who received interval debulking surgery had shorter TTNT and OS than patients at stage III or who received primary debulking surgery, respectively. OS was worse in patients with residual disease and in BRCA wild-type. Conclusion: Multiple factors were associated with shorter TTNT or OS in this retrospective real-world analysis.

Increased risk of brain metastases in ovarian cancer patients with BRCA mutations.

PURPOSE: To estimate the risk for brain metastases in patients with ovarian cancer using real-world data, and assess whether BRCA mutations increase that risk. METHODS: This retrospective study included 4515 patients diagnosed with ovarian cancer between January 1, 2011, and January 31, 2018, from the Flatiron Health database, a longitudinal, demographically, and geographically diverse database derived from electronic health records in the United States. RESULTS: Forty-six (1%) patients were diagnosed with brain metastases after being diagnosed with ovarian cancer. Of 4515 patients with ovarian cancer, 10% had a known BRCA mutation, 37% had BRCA wildtype (BRCAwt), and the BRCA status of the remaining 51% was unknown/untested. Brain metastases were observed in 3% of patients with BRCA mutations compared with 0.6% of those with BRCAwt. The Kaplan-Meier estimate for the proportion of patients with brain metastases within 5 years of diagnosis was 5.7% in the population with BRCA mutations compared with 1.4% in those with BRCAwt (hazard ratio 4.44; 95% confidence interval, 1.97, 10.00; P < 0.0001). These data demonstrate that patients with a BRCA mutation had a significantly higher risk for brain metastases than those without. CONCLUSION: Despite being a rare manifestation of ovarian cancer, the possibility of developing brain metastases should be considered in these patients, especially in patients with a BRCA mutation. The availability of new therapeutic options that may prolong overall survival and may not cross the blood-brain barrier could also lead to an increase in brain metastases in patients with ovarian cancer.