Background: In the CASPIAN trial, durvalumab + chemotherapy demonstrated significant improvements in overall survival compared with chemotherapy alone in patients with extensive-stage small cell lung cancer (SCLC). We aimed to assess the cost-effectiveness of durvalumab in patients with extensive-stage SCLC from the US healthcare system perspective. Patients and Methods: A comprehensive Markov model was adapted to evaluate cost and effectiveness of durvalumab combination versus platinum/etoposide alone in the first-line therapy of extensive-stage SCLC based on data from the CASPIAN study. The main endpoints included total costs, life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-e-ectiveness ratios (ICERs). Model robustness was assessed with sensitivity analysis, and additional subgroup analyses were also performed. Results: Durvalumab + chemotherapy therapy resulted in an additional 0.27 LYs and 0.20 QALYs, resulting in an ICER of $464,711.90 per QALY versus the chemotherapy treatment. The cost of durvalumab has the greatest inﬂuence on this model. Subgroup analyses showed that the ICER remained higher than $150,000/QALY (the willingness-to-pay threshold in the United States) across all patient subgroups. Conclusions: Durvalumab in combination with platinum/etoposide is not a cost-effective option in the first-line treatment of patients with extensive-stage SCLC.
Dong Ding, Huabin Hu, Shuosha Li, Youwen Zhu, Yin Shi, Mengting Liao, Jin Liu, Xu Tian, Aiting Liu, and Jin Huang
Jessica S.W. Borgers, Richard P. Tobin, Robert J. Torphy, Victoria M. Vorwald, Robert J. Van Gulick, Carol M. Amato, Dasha T. Cogswell, Tugs-Saikhan Chimed, Kasey L. Couts, Adrie Van Bokhoven, Christopher D. Raeburn, Karl D. Lewis, Joshua Wisell, Martin D. McCarter, Rao R. Mushtaq, and William A. Robinson
Background: Adrenal gland metastases (AGMs) are common in advanced-stage melanoma, occurring in up to 50% of patients. The introduction of immune checkpoint inhibitors (ICIs) has markedly altered the outcome of patients with melanoma. However, despite significant successes, anecdotal evidence has suggested that treatment responses in AGMs are significantly lower than in other metastatic sites. We sought to investigate whether having an AGM is associated with altered outcomes and whether ICI responses are dampened in the adrenal glands. Patients and Methods: We retrospectively compared ICI responses and overall survival (OS) in 68 patients with melanoma who were diagnosed with an AGM and a control group of 100 patients without AGMs at a single institution. Response was determined using RECIST 1.1. OS was calculated from time of ICI initiation, anti–PD-1 initiation, initial melanoma diagnosis, and stage IV disease diagnosis. Tumor-infiltrating immune cells were characterized in 9 resected AGMs using immunohistochemical analysis. Results: Response rates of AGMs were significantly lower compared with other metastatic sites in patients with AGMs (16% vs 22%) and compared with those without AGMs (55%). Patients with AGMs also had significantly lower median OS compared with those without AGMs (3.1 years vs not reached, respectively). We further observed that despite this, AGMs exhibited high levels of tumor-infiltrating immune cells. Conclusions: In this cohort of patients with melanoma, those diagnosed with an AGM had lower ICI response rates and OS. These results suggest that tissue-specific microenvironments of AGMs present unique challenges that may require novel, adrenal gland–directed therapies or surgical resection.
Rongbo Lin, Sunzhi Lin, Shuitu Feng, Qingyi Wu, Jianqian Fu, Fang Wang, Hui Li, Xiaofeng Li, Gaowang Zhang, Yongzhi Yao, Min Xin, Tianyang Lai, Xia Lv, Yigui Chen, Shangwang Yang, Yubiao Lin, Lixia Hong, Zhenyu Cai, Jianfeng Wang, Gen Lin, Shaowei Lin, Shen Zhao, Jinfeng Zhu, and Cheng Huang
Background: Opioid titration is necessary to achieve rapid, safe pain relief. Medication can be administered via patient-controlled analgesia (PCA) or by a healthcare provider (non-PCA). We evaluated the efficacy of intravenous PCA versus non-PCA hydromorphone titration for severe cancer pain (≥7 at rest on the 11-point numeric rating scale [NRS]). Patients and Methods: Patients with severe cancer pain were randomized 1:1 to PCA or non-PCA titration, stratified by opioid-tolerant or opioid-naïve status. The PCA pump was set to no continuous dose, with a hydromorphone bolus dose 10% to 20% of the total previous 24-hour equianalgesic (for opioid-tolerant patients) or 0.5 mg (for opioid-naïve patients). For the non-PCA group, the initial hydromorphone bolus dose was identical to that in the PCA group, with the subsequent dose increased by 50% to 100% (for NRS unchanged or increased) or repeated at the current dose (for NRS 4–6). Hydromorphone delivery was initiated every 15 minutes (for NRS ≥4) or as needed (for NRS ≤3). The primary endpoint was time to successful titration (TST; time from first hydromorphone dose to first occurrence of NRS ≤3 in 2 consecutive 15-minute intervals). Results: Among 214 patients (PCA, n=106; non-PCA, n=108), median TSTs (95% CI) were 0.50 hours (0.25–0.50) and 0.79 hours (0.50–1.42) for the PCA and non-PCA groups, respectively (hazard ratio [HR], 1.64; 95% CI, 1.23–2.17; P=.001). TSTs in opioid-tolerant patients were 0.50 hours (0.25–0.75) and 1.00 hours (0.50–2.00) for the PCA and non-PCA groups, respectively (HR, 1.92; 95% CI, 1.32–2.78; P=.003); in opioid-naive patients, TST was not significantly different for the PCA versus non-PCA groups (HR, 1.35; 95% CI, 0.88–2.04; P=.162). Pain score (median NRS; interquartile range) over 24 hours was significantly lower in the PCA group (2.80; 2.15–3.22) than in the non-PCA group (3.00; 2.47–3.53; P=.020). PCA administration produces significantly higher patient satisfaction with pain control than non-PCA administration (P<.001). Conclusions: Intravenous hydromorphone titration for severe cancer pain was achieved more effectively with PCA than with non-PCA administration.
Courtney Lawhn Heath, Laura J. Esserman, Robert R. Flavell, and Michelle E. Melisko
Daniel J. Boffa, Keith B. Churchwell, and Richard C. Maduka
Jeffrey S. Dome, Elizabeth A. Mullen, David B. Dix, Eric J. Gratias, Peter F. Ehrlich, Najat C. Daw, James I. Geller, Murali Chintagumpala, Geetika Khanna, John A. Kalapurakal, Lindsay A. Renfro, Elizabeth J. Perlman, Paul E. Grundy, and Conrad V. Fernandez
Refinements in surgery, radiation therapy, and chemotherapy since the mid-20th century have resulted in a survival rate exceeding 90% for patients with Wilms tumor (WT). Although this figure is remarkable, a significant proportion of patients continue to have event-free survival (EFS) estimates of <75%, and nearly 25% of survivors experience severe chronic medical conditions. The first-generation Children’s Oncology Group (COG) renal tumor trials (AREN ‘0’), which opened to enrollment in 2006, focused on augmenting treatment regimens for WT subgroups with predicted EFS <75% to 80%, including those with the adverse prognostic marker of combined loss of heterozygosity (LOH) at chromosomes 1p/16q, pulmonary metastasis with incomplete lung nodule response after 6 weeks of chemotherapy, bilateral disease, and anaplastic histology. Conversely, therapy was reduced for patient subgroups with good outcomes and potential for long-term toxicity, such as those with lung metastasis with complete lung nodule response after 6 weeks of chemotherapy. This article summarizes the key findings of the first-generation COG renal tumor studies and their implications for clinical practice.
David Groheux, Elif Hindié, Marc Espié, and Gary A. Ulaner
Reece J. Knippel and Cynthia L. Sears
The human gut microbiome has an ever-increasing role in the instigation and progression of colorectal cancer (CRC). Recent investigations have focused on identifying the key causative bacterial species and the composition and structure of the microbiome as a whole that ultimately lead to tumorigenesis in the colon. Understanding the bacterial mechanisms that promote CRC provides a rich area for the development of new screening modalities and therapeutics that may improve patient outcomes. This article reviews the various mechanisms that bacteria in the gut use to induce and/or promote tumor formation, discusses the application of the microbiome in the prevention and therapy of CRC, and provides directions for future research endeavors aiming to develop a more complete understanding of this complex phenomenon.