Endometrial cancer (EC) is the most common gynecologic malignancy, with worldwide increasing incidence and disease-associated mortality. Although most patients with EC are diagnosed with early-stage disease, systemic treatment options for patients with advanced or recurrent EC have historically been limited. EC-focused clinical trials and the ensuing therapeutic landscape have expanded since The Cancer Genome Atlas (TCGA) identified 4 distinct EC subgroups associated with differential survival. This endeavor revolutionized our understanding of the genomic characterization of EC as well as molecular drivers of this heterogeneous malignancy, leading to precision oncology approaches to therapeutics and advancement in treatment options. This review describes the current status of and recent advancements in therapeutic options for patients with advanced and recurrent EC. The NCCN Guidelines for Uterine Neoplasms provide detailed recommendations regarding the diagnosis, workup, and management of EC.
Current Evidence-Based Systemic Therapy for Advanced and Recurrent Endometrial Cancer
Sushmita Gordhandas, William A. Zammarrelli III, Eric V. Rios-Doria, Angela K. Green, and Vicky Makker
Therapy for Older AML Patients: The Role of Novel Agents and Allogeneic Stem Cell Transplant
Jeffrey E. Lancet and Sergio Giralt
The development of novel therapeutics in acute myeloid leukemia (AML) is driven by the need to improve efficacy and reduce toxicity. Clearly, elderly patients with AML represent a highly heterogeneous group, based on a wide array of disease- and patient-specific characteristics. Therefore, novel treatment strategies aimed at overcoming specific biologic modifiers of disease resistance will be paramount to successful therapy for some, whereas in others, the ability to administer a low-toxicity regimen on a chronic basis to achieve disease control may prove beneficial, perhaps even in the absence of complete responses. In addition, identifying genomic and proteomic expression patterns using an individual's unique neoplastic clone will likely optimize the ability to predict responders to novel therapies and identify new and relevant therapeutic targets. The development of reduced-intensity preparative regimens for allogeneic transplants has allowed physicians and patients to explore the option of long-term disease control. The risk–benefit ratio for this procedure will depend on the disease state, patient performance status, and comorbidities. However, current results underscore that age alone should no longer be a contraindication for allogeneic transplant with curative intent in these patients, and long-term disease control with good quality of life is possible and can be expected. Future trials combining the novel therapies described in this article and novel transplant technologies should allow more elderly patients with AML or myelodysplastic syndromes to experience long and productive lives.
Novel Systemic Therapies for Small Cell Lung Cancer
Charles M. Rudin, Christine L. Hann, Craig D. Peacock, and D. Neil Watkins
A diagnosis of small cell lung cancer (SCLC) today confers essentially the same terrible prognosis that it did 25 years ago, when common use of cisplatin-based chemotherapy began for this disease. In contrast to past decades of research on many other solid tumors, studies of combination chemotherapy using later generation cytotoxics and targeted kinase inhibitors have not had a significant impact on standard care for SCLC. The past few years have seen suggestions of incrementally improved outcomes using standard cytotoxics, including cisplatin-based combination studies of irinotecan and amrubicin by Japanese research consortia. Confirmatory phase III studies of these agents are ongoing in the United States. Antiangiogenic strategies are also of primary interest and are in late-phase testing. Several novel therapeutics, including high-potency small molecule inhibitors of Bcl-2 and the Hedgehog signaling pathway, and a recently discovered replication-competent picornavirus, have shown remarkable activity against SCLC in preclinical models and are currently in simultaneous phase I clinical development. Novel therapeutic approaches based on advances in understanding of the biology of SCLC have the potential to radically change the outlook for patients with this disease.
Novel Agents for Metastatic Triple-Negative Breast Cancer: Finding the Positive in the Negative
Neelima Vidula, Leif W. Ellisen, and Aditya Bardia
Metastatic triple-negative breast cancer (TNBC) is associated with a poor prognosis, and the development of better therapeutics represents a major unmet clinical need. Although the mainstay of treatment of metastatic TNBC is chemotherapy, advances in genomics and molecular profiling have helped better define subtypes of TNBC with distinct biologic drivers to guide the therapeutic development of targeted therapies, including AKT inhibitors for PI3K/AKT-altered TNBC, checkpoint inhibitors for PD-L1–positive TNBC, and PARP inhibitors for BRCA1/2 mutant TNBC. This progress may ultimately convert TNBC from a disease traditionally defined by the absence of therapeutically actionable receptors to one that is defined by the presence of discrete molecular targets with therapeutic implications. Furthermore, antibody drug conjugates have emerged as an important therapeutic strategy to target genomically complex tumors that lack actionable oncogenes but have overexpressed actionable surface receptors such as trop-2. In this article, we discuss promising novel agents for advanced TNBC, some of which have been incorporated into current clinical practice, and others that will likely change the therapeutic landscape and redefine the TNBC terminology in the near future.
Pilot Randomized Controlled Trial of an Educational Video for CAR T-Cell Therapy Recipients
P. Connor Johnson, Tejaswini Dhawale, Richard A. Newcomb, Ana Barata, Kyle Karpinski, Mitchell W. Lavoie, Dagny Vaughn, Kathleen Hennessey, David Schneider, Hermioni L. Amonoo, Angelo Volandes, and Areej El-Jawahri
Background: CAR T-cell therapy has transformed the treatment of hematologic malignancies, but it is complex and challenging to convey to patients. Educational video interventions are efficacious for improving patient knowledge about cancer therapeutics and informing their care preferences, yet no educational videos have been evaluated in CAR T-cell therapy. Methods: We conducted a randomized controlled trial comparing an educational video versus usual care in adults (age ≥18 years) with hematologic malignancies receiving CAR T-cell therapy at Massachusetts General Hospital. Intervention participants watched a 13-minute video depicting how CAR T-cell therapy works, logistics, toxicities, prognosis, recovery, and approaches for dealing with prognostic uncertainty. The primary outcome was feasibility (≥60% enrollment rate). Secondary outcomes included acceptability (≥80% reporting comfort with the video), patients’ knowledge about CAR T-cell therapy (10-item test), and self-efficacy (Communication and Attitudinal Self-Efficacy Scale–Cancer), decision satisfaction (Decision Conflict Scale), psychological distress (Hospital Anxiety and Depression Scale), and preference for CAR T-cell therapy. Results : We enrolled 79% (80/101) of eligible patients. Of that group, 91% (30/33) reported being very or somewhat comfortable watching the video, and 94% (31/33) would definitely or probably recommend the video. At 1 month, participants in the video arm reported higher self-efficacy (mean difference [MD], 9.2 [95% CI, –4.0 to 22.3]; Cohen’s d, 0.32), decision satisfaction (MD, 2.5 [95% CI, 0.7–4.2]; Cohen’s d, 0.67), and lower anxiety (MD, –0.8 [95% CI, –2.5 to 0.7]; Cohen’s d, 0.26) compared with participants in the usual care arm. At 1 week, both arms reported high preferences for CAR T-cell therapy (video arm, 94% [33/35]; usual care, 84% [27/32]). Conclusions: We found that an educational video for patients receiving CAR T-cell therapy was feasible and acceptable. The educational video demonstrated promising preliminary effects on patient self-efficacy and decision satisfaction and warrants further study.
Erratum to: NCCN Guidelines® Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 3.2022
Seagen Inc. This activity is supported by a medical education grant from Karyopharm ® Therapeutics. This activity is supported through an Independent Medical Education grant from Merck & Co., Inc. This has been corrected online. The editors and
by a medical education grant from Karyopharm Therapeutics. A corrected copy of the article is available online at JNCCN.org . The editorial office apologizes for this error.
Bringing Science to Clinical Practice
refresher on the rationale for and the use of new targeted therapeutics, this is for you. And in terms of providing direction on unique patients or small subsets, it’s just a start. In a few months, you’ll notice a new feature in JNCCN , “Molecular Insights
Speeding Access to Precision Oncology Drugs: How Are We Doing With Biomarker-Driven Drug Approvals?
bring new cancer therapeutics to the patients who need them. It is important to evaluate the use of appropriate clinical parameters in these studies that are considered during novel biomarker-driven precision oncology drug approval. In this issue of
Predictive Biomarkers in Advance of a Companion Drug: Ahead of Their Time?
Robin K. Kelley, Chloe Atreya, Alan P. Venook, and Phillip G. Febbo
remain in clinical development with unproven clinical benefit. The discordant commercial maturation of therapeutics and their companion biomarkers arises largely from disparate development and regulatory environments and, ultimately, leads to the question