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ASCO guidelines cite significant improvement in progression-free survival when PARP inhibitors are used as maintenance therapy or in the setting of recurrent disease in women with advanced ovarian cancer who have responded to platinum-based chemotherapy in the first line.
In an analysis of the phase 3 PRIMA study, niraparib monotherapy as first-line maintenance after platinum-based chemotherapy improved progression-free survival in women with newly diagnosed advanced ovarian cancer regardless of BRCA mutation status or homologous recombination status (deficient or proficient).
In the PAOLA-1 study, women with advanced ovarian cancer, regardless of BRCA mutation status, experienced a 40% reduction in the risk for disease progression or death when randomized to olaparib plus bevacizumab compared with placebo and bevacizumab. The reduction in risk with olaparib was greatest in patients whose tumors were homologous recombination deficient.
In a 4-arm randomized study, providing telephone genetic counseling only to those women who have a pathogenic mutation or who request the counseling is noninferior to mandatory pre- and posttest counseling, which may represent a new paradigm for genetic testing.
Rearrangement during transfection (RET) fusions can result in gain- or loss-of-function mutations and unchecked cellular proliferation. Although RET fusions are present in only a small percentage of cases of non–small-cell lung cancer, evidence shows they may be meaningful drug targets.
There are several oncogenic driver mutations that are actionable for treatment in cases of NSCLC. Evidence has shown that molecularly targeted approaches can result in positive outcomes for patients with NSCLC, underscoring the importance of research into biomarker testing and molecular profiling.
Four retrospective studies on treatment with immune checkpoint inhibitors in patients with NSCLC have shown only limited clinical benefit in patients with RET-rearranged lung cancer.
Ongoing trials of two recently approved RET inhibitors, pralsetinib and selpercatinib, are producing encouraging safety and efficacy data in patients with RET fusion–positive NSCLC.
Although researchers have made great advances in NSCLC screening, diagnosis, and treatment, there remain several areas of unmet need, including the development of individual risk-based screening criteria, research into optimal biopsy types for molecular profiling, and greater focus on effective side-effect management plans for patients on multimedication regimens.
In the phase 2 OVARIO study, median progression-free survival has not yet been reached in women with advanced ovarian cancer who are being treated with the combination of niraparib and bevacizumab after response to first-line platinum-based chemotherapy plus bevacizumab. The combination did not appear to cause cumulative toxicities.
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