Background: We evaluated the impact of gastroenterology/hepatology consultation, as recommended by guidelines, on the management of severe immune checkpoint inhibitor (ICI)–induced hepatitis. Methods: We conducted a multicenter, retrospective cohort study of 294 patients who developed grade ≥3 (alanine aminotransferase [ALT] >200 U/L) ICI-induced hepatitis, with early gastroenterology/hepatology consultation defined as occurring within 7 days of diagnosis. The primary outcome was time to ALT normalization (≤40 U/L), and the secondary outcome was time to ALT improvement to ≤100 U/L. Results: A total of 117 patients received early consultation. In the 213 patients with steroid-responsive hepatitis, early consultation was not associated with faster ALT normalization (hazard ratio [HR], 1.12; 95% CI, 0.83–1.51; P=.453). A total of 81 patients developed steroid-refractory hepatitis, with 44 (54.3%) receiving early consultation. In contrast to the patients whose hepatitis responded to steroid treatment, early consultation in those with steroid-refractory disease was associated with faster ALT normalization (HR, 1.89; 95% CI, 1.12–3.19; P=.017) and ALT improvement to ≤100 U/L (HR, 1.72; 95% CI, 1.04–2.84; P=.034). Notably, additional immunosuppressive therapy for steroid-refractory disease was initiated sooner after diagnosis in the early consult group (median 7.5 vs 13.0 days; log-rank P=.001). When time to additional immunosuppression was added as a covariate to the Cox model in mediation analysis, early consultation was no longer associated with time to ALT normalization (HR, 1.39; 95% CI, 0.82–2.38; P=.226) or with time to ALT improvement to ≤100 U/L (HR, 1.25; 95% CI, 0.74–2.11; P=.404). Time to additional immunosuppression remained associated with faster ALT normalization and faster ALT improvement to ≤100 U/L in the model, suggesting that the faster hepatitis resolution in the early consultation group was primarily attributable to earlier initiation of additional immunosuppression. Conclusions: Early gastroenterology/hepatology consultation is associated with faster resolution of biochemical abnormalities in patients with steroid-refractory hepatitis. This beneficial effect appears to be mediated by earlier initiation of additional immunosuppressive therapy in those receiving early consultation.
Early Liver Specialist Consultation is Associated With Faster Biochemical Resolution of Severe Immune Checkpoint Inhibitor–Induced Hepatitis
Michael Li, Danny Wong, Jordan S. Sack, Alexander S. Vogel, F. Stephen Hodi, Lawrence Fong, Jennifer C. Lai, Shilpa Grover, and Stephen D. Zucker
Emerging Therapies in the Treatment of Bladder Cancer
Presented by: Arlene O. Siefker-Radtke
The advent of targeted agents, such as enfortumab vedotin, erdafitinib, and sacituzumab govitecan, have revolutionized the treatment of metastatic urothelial cancer. Although these novel therapies have demonstrated favorable efficacy outcomes, their toxicity must be carefully monitored. The NCCN Guidelines for Bladder Cancer recommend platinum-based chemotherapy in this clinical context, but the combination of targeted and immunotherapeutic agents may have the potential to replace it as frontline standard of care.
Health System Recruitment and Retention Strategies: A Plenary Session
Presented by: Rebecca L. Caires, Anne H. Gross, Todd A. Pickard, and Kristi Stiffler
Moderated by: Timothy Kubal
Recruitment and retention in healthcare were uniquely impacted by the COVID-19 pandemic. An existing workforce shortage was significantly exacerbated by high attrition, early retirements, and people leaving healthcare altogether because of burnout and exhaustion. Since the pandemic crisis has eased, individuals have shown the desire for healthier work–life balance and opportunities for remote or hybrid work environments with clearly defined career paths. Recognizing this shift and aligning with the current environment are imperative to recruiting and retaining employees in healthcare. At the NCCN 2023 Annual Conference, a panel of experts from 5 major academic oncology centers shared their struggles with recruitment and retention (both before and after the COVID-19 pandemic) and offered valuable insight into some of the systems and processes they’ve since implemented to attract desirable candidates, make them feel heard and appreciated, and retain them in the long run.
Hereditary/Familial Ovarian Cancer: Testing Principles and Risk Management
Presented by: Leigha Senter
Although BRCA1 and BRCA2 pathogenic or likely pathogenic variants are a well-established cause of hereditary ovarian cancer, recent studies have brought other homologous recombination repair pathway genes into the limelight. The current NCCN Guidelines reflect the most up-to-date, evidence-based data relating to the risk management of patients who are carriers of BRCA1/2 and/or other variants. Risk-reducing bilateral salpingo-oophorectomy is the current standard of care, but a recommendation for salpingectomy alone may be on the horizon.
Highlights of the NCCN Oncology Research Program
Increasing Private Payer and Medicare Coverage of Circulating Tumor DNA Tests: What’s at Stake?
Mariana P. Socal
Influence of Food With Different Fat Concentrations on Alectinib Exposure: A Randomized Crossover Pharmacokinetic Trial
Daan A.C. Lanser, Simon P. de Leeuw, Esther Oomen-de Hoop, Peter de Bruijn, Marthe S. Paats, Daphne W. Dumoulin, Stijn L.W. Koolen, Anne-Marie C. Dingemans, Ron H.J. Mathijssen, and G.D. Marijn Veerman
Background: Alectinib is the keystone treatment in advanced anaplastic lymphoma kinase–positive (ALK+) non–small cell lung cancer (NSCLC). An exposure–response threshold of 435 ng/mL has recently been established, albeit 37% of patients do not reach this threshold. Alectinib is orally administered, and absorption is largely influenced by food. Hence, further investigation into this relationship is needed to optimize its bioavailability. Patients and Methods: In this randomized 3-period crossover clinical study in ALK+ NSCLC, alectinib exposure was compared among patients with different diets. Every 7 days, the first alectinib dose was taken with either a continental breakfast, 250-g of low-fat yogurt, or a self-chosen lunch, and the second dose was taken with a self-chosen dinner. Sampling for alectinib exposure (Ctrough) was performed at day 8, just prior to alectinib intake, and the relative difference in Ctrough was compared. Results: In 20 evaluable patients, the mean Ctrough was 14% (95% CI, −23% to −5%; P=.009) and 20% (95% CI, −25% to −14%; P<.001) lower when taken with low-fat yogurt compared with a continental breakfast and a self-chosen lunch, respectively. Administration with a self-chosen lunch did not change exposure compared with a continental breakfast (+7%; 95% CI, −2% to +17%; P=.243). In the low-fat yogurt period, 35% of patients did not reach the threshold versus 5% with the other meals (P<.01). Conclusions: Patients and physicians should be warned for a detrimental food–drug interaction when alectinib is taken with low-fat yogurt, because it results in a clinically relevant lower alectinib exposure. Intake with a self-chosen lunch did not change drug exposure and could be a safe and patient-friendly alternative.
Laboratory Selection in Germline Genetic Testing: Laboratory Science Matters
Suzanne M. Mahon
There are multiple laboratories that offer germline genetic testing, and it can be difficult to discern which one to use for testing. Some laboratories have more comprehensive analysis techniques and capability, which increases the accuracy of testing. The ordering provider has a responsibility to select the appropriate laboratory with technologic capability for the needed testing, inform the laboratory of prior testing results in the patient and family so known familial variants have targeted testing, and use appropriate terminology and nomenclature when communicating information to other healthcare professionals, patients, and families. This report presents a case illustrating the potential errors that can occur when a provider selects a laboratory that lacks the capacity to detect certain pathogenic variants, such as large deletions and duplications. False-negative germline testing results lead to missed opportunities in prevention and early detection for not only the patient but often multiple family members, which may lead to psychosocial distress and late-detected cancers. This case highlights the complexities of genetic care and why management by a genetics professional can facilitate more fiscally responsible care, appropriate genetic testing, and comprehensive care for all family members at risk.
Management of Advanced Ovarian, Fallopian Tube, and Primary Peritoneal Cancers
Presented by: Joyce F. Liu
Treatment approaches for advanced ovarian cancer should consider several factors. Among the most important are platinum sensitivity, the status of BRCA and homologous recombination deficiency (HRD), and the changing indications for PARP inhibitors in recurrent disease and maintenance. PARP inhibitors have demonstrated clear benefit in patients with BRCA mutated tumors, especially in the first-line setting, and HRD testing can guide their use for patients without BRCA mutations. A new antibody–drug conjugate, mirvetuximab soravtansine, has been approved for use in a subset of patients with platinum-resistant disease. Newly diagnosed patients with advanced-stage ovarian, fallopian tube, or primary peritoneal cancers should always be evaluated by a gynecologic oncologist if possible.
Management of Metastatic Prostate Cancer
Presented by: Archana Ajmera, Rana R. McKay, and Kelly L. Stratton
Androgen deprivation therapy is a well-established standard of care for the management of metastatic prostate cancer; however, recent studies have investigated additional therapeutic options, escalation strategies, and primary directed therapy for patients with advanced disease. Treatment decisions are based on clinical parameters, disease characteristics, and patient factors. At the NCCN 2023 Annual Conference, a panel of experts used 3 case studies to develop an evidence-based approach for the treatment of patients with metastatic prostate cancer. The session focused on the current research regarding both systemic and local therapy options in each clinical context.