The oncologist
-
Randomized Controlled Trial
Amplifying Outcomes: Checkpoint Inhibitor Combinations in First-Line Non-Small Cell Lung Cancer.
Lung cancer is one of the most common types of cancer, resulting in approximately 1.8 million deaths worldwide. Immunotherapy using checkpoint inhibitors has become standard of care in advanced non-small cell lung cancer (NSCLC), and there is increasing interest in further improving outcomes through combination with other therapeutics. This systematic review evaluates emerging phase III data on the efficacy and safety of checkpoint inhibitor combinations as first-line treatment for advanced NSCLC. ⋯ Single-agent immune checkpoint inhibitors are now standard of care for advanced non-small cell lung cancer (NSCLC), and emerging data show that combining these agents with established chemotherapy further improves outcomes. The phase III KEYNOTE-189 and IMPower-130 trials showed significantly improved survival using this strategy for nonsquamous NSCLC, and the phase III KEYNOTE-407 trial showed similar results in squamous disease. Checkpoint inhibitor combinations are therefore an important new treatment option for first-line NSCLC. Programmed death ligand-1 expression may inform the use of checkpoint inhibitor combination therapy, and overall tumor mutation burden is also an emerging biomarker for this new treatment strategy.
-
Review
Perspectives on Treatment of Metastatic Colorectal Cancer with Immune Checkpoint Inhibitor Therapy.
Despite lengthening survival, death rates from metastatic colorectal cancer (CRC) remain unacceptably high, with a bright spot being the demonstration of durable responses in patients with CRC who have mismatch repair-deficient (dMMR) and/or microsatellite instability-high (MSI-H) tumors and are treated with immune checkpoint inhibitor therapy. Nivolumab and pembrolizumab, as well as nivolumab in combination with low-dose ipilimumab-all checkpoint inhibitors-are currently approved by the U. S. ⋯ Food and Drug Administration approval of the immune checkpoint inhibitors nivolumab (with or without low-dose ipilimumab) and pembrolizumab in this population. Combination therapy (e.g., nivolumab with low-dose ipilimumab) has demonstrated numerically higher response rates and improved long-term clinical benefit relative to anti-programmed death-1 monotherapy. Ongoing trials are evaluating immunotherapy in the broader CRC population and novel combinations to optimize immunotherapy for advanced CRC.
-
Hairy cell leukemia (HCL) is an indolent B-cell malignancy characterized by high initial sensitivity to purine analog chemotherapy, minimal residual disease (MRD) frequently accompanying complete remission (CR), and relapses requiring additional treatment. Repeat chemotherapy shows decreasing efficacy and increasing toxicity with each course. Newer therapies targeting BRAF/MEK or Bruton's tyrosine kinase are effective but generally leave MRD. ⋯ Despite these therapies, relapse occurs, and moxetumomab pasudotox has an important role in relapsed and refractory HCL because of its ability to achieve high rates of complete remissions (CRs) without chemotherapy; most of these CRs are without minimal residual disease (MRD). CR duration is enhanced in patients who achieve eradication of MRD. To improve the efficacy of this recombinant immunotoxin, a phase I trial is underway in combination with rituximab to reduce tumor burden and decrease immunogenicity.
-
Trifluridine and tipiracil (FTD + TPI) and regorafenib (REG) are approved treatments for the treatment of refractory metastatic colorectal cancer (mCRC). This study assesses adherence and duration of therapy with FTD + TPI versus REG and explores the effect of sequencing on adherence. ⋯ Trifluridine plus tipiracil (FTD + TPI) and regorafenib (REG) prolong survival in refractory metastatic colorectal cancer (mCRC) but have different tolerability profiles. This study assessed real-world adherence to treatment with FTD + TPI versus REG and compared outcomes among patients who switched from FTD + TPI to REG and vice versa. FTD + TPI was associated with significantly higher medication adherence and longer time to discontinuation than REG. Patients treated with FTD + TPI prior to switching to REG also showed higher adherence outcomes. Findings could help inform decision making regarding the choice and sequencing of treatment with FTD + TPI versus REG in patients with mCRC.
-
Oncology research increasingly involves biospecimen collection and data sharing. Ethical challenges emerge when researchers seek to use archived biospecimens for purposes that were not well defined in the original informed consent document (ICD). We sought to inform ongoing policy debates by assessing patient views on these issues. ⋯ This survey evaluated views of patients with cancer regarding the permissible use of stored biospecimens from cancer trials when modern scientific methods are not well described in the original informed consent document. The vast majority of patients support translational research and expect that any biospecimens they donate will be used to advance knowledge. When researchers, policy makers, and those charged with research oversight debate use of stored biospecimens, it is important to recognize that research participants have an interest in productive use of their blood, tissue, or data, in addition to considerations of risks and the adequacy of documented consent.