China 
Africa 
Explore chapters and articles related to this topic
Patient Centricity and Precision Medicine
Published in Kelly H. Zou, Lobna A. Salem, Amrit Ray, Real-World Evidence in a Patient-Centric Digital Era, 2023
Diana Morgenstern, Mina B. Riad, Claudia Zavala, Amrit Ray
Several examples illustrate the use of RWD to help capture the patient voice. In cancer research, PROs such as progression-free survival, overall survival, and toxicities can be gathered to complement data from clinical trials and get a more complete picture of how patients respond to treatment (Klink, 2020). Noona, a smart cloud-based mobile service, allows oncology patients to report real-time symptoms and lets their healthcare providers access that information in order to better recognize early warning signs and send tailored self-care instructions, schedule a clinic visit, or evaluate possible treatment changes (Conquer Magazine, 2020). HealthTree is a software tool that allows multiple myeloma patients to enter their information into a large patient network (Conquer Magazine, 2020). This tool was developed based on the finding that electronic health records only capture about 8% of patients’ complete data, leading to a gap in relevant information collected. As such, HealthTree makes a point of collecting data regarding questions not typically captured by health care providers (HCPs), such as, “What can you do on your own?” “Do you have an autoimmune disorder?” and “Do you have quality- of-life issues?” The responses give researchers access to ample information that may help them to answer scientific questions in ways that cannot be tackled by oncology clinical trials.
Survival Analysis
Published in Trevor F. Cox, Medical Statistics for Cancer Studies, 2022
We will use data from a lung cancer clinical trial[50] that tested the efficacy of maintenance therapy (treatment usually given after initial treatment) for small-cell lung cancer. Patients who had not progressed after initial chemotherapy were randomised to maintenance therapy by Sunitinib or Placebo. The primary endpoint was progression-free survival. The data are available from “Project Data Sphere”, a platform for openly sharing cancer data (www.projectdatasphere.org; see doi.org/10.34949/zbwg-ef42 for this particular trial).
Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Due to its success in the clinic, bevacizumab is now approved for colon, kidney, lung, ovarian, and breast cancers, and glioblastoma, although approvals vary between countries. It has been found to increase the duration of progression-free survival, and rate and duration of response in all of these cancers. However, it is important to note that, due to its mechanism of action, bevacizumab is always used in combination with other agents. For example, it has been approved for first-line treatment of metastatic breast cancer in combination with paclitaxel or docetaxel, for advanced or metastatic renal cell carcinoma in combination with interferon alpha-2a, and in combination with platinum-based agents for the first-line treatment of unresectable advanced, metastatic, or recurrent non-small-cell lung cancer. Bevacizumab is also being evaluated for use in other types of solid tumors, including prostate, melanoma, and some hematologic malignancies.
Immunosuppressive tumor microenvironment modulation by chemotherapies and targeted therapies to enhance immunotherapy effectiveness
Published in OncoImmunology, 2022
Robby Barnestein, Loïck Galland, Laura Kalfeist, François Ghiringhelli, Sylvain Ladoire, Emeric Limagne
Alpelisib, another treatment used for advanced HR+PIK3CA-mutated BC, seems able to modulate anti-tumor immunity. Indeed, this PI3K inhibitor could significantly deplete MDSCs and Treg populations, either alone147 or in association with ribociclib,124 thereby improving responsiveness of BC including TNBC to immunotherapy by increasing PD-L1 expression in preclinical models.148 A clinical trial (NCT04317105) evaluating copanlisib, another PI3K inhibitor, with immunotherapy (nivolumab ± ipilimumab) is currently recruiting patients with advanced solid tumor and changes in the PIK3CA gene. Regarding other therapeutics that act on the PI3K/AKT/mTOR pathway, we can also mention ipatasertib, which was initially evaluated in a phase III trial in combination with paclitaxel in patients with metastatic TNBC.149 This study was negative in terms of its primary endpoint, with no improvement in progression-free survival. However, ipatasertib efficiently depletes Foxp3+ regulatory T cells in the TME, resulting in increased infiltration of effector T cells.150 For these reasons, a trial evaluating ipatasertib in combination with atezolizumab in patients with advanced solid tumors with PI3K pathway hyperactivation is currently ongoing (IceCAP, NCT03673787).
Pre-clinical models of small cell lung cancer and the validation of therapeutic targets
Published in Expert Opinion on Therapeutic Targets, 2020
Jane S. Y. Sui, Petra Martin, Steven G. Gray
DLL3 expression was also recently assessed in a CTC-driven biomarker study of SCLC patient responses to etoposide/platinum [120]. Remarkably it emerged that in this study of n = 108 treatment-naïve patients, baseline samples were taken from all patients, after one chemotherapy cycle (n = 68 patients; post-first cycle sample) and at the time of disease progression, before the initiation of second-line treatment (n = 48 patients; disease progression sample). The expression of DLL3, cytokeratins (CK), CD45, and vimentin (Vim) was characterized on the isolated CTCs from these samples. The most important finding was that prior to treatment, 74.1% of patients had detectable DLL3+/CD45− CTCs. One-treatment cycle significantly decreased both the detection rate (p < 0.001) and the absolute number (p < 0.001) of the DLL3+/CD45− CTCs and were associated with (a) significantly decreased progression-free survival at baseline and (b) with significantly decreased overall survival on disease progression [120]. Despite the apparent set-backs with DLL3 targeting agents, a recent study using cell lines and patient PDX models identified an LSD1-NOTCH-ASCL1 axis that was sensitive to LSD1 inhibitors [121] (Figure 1, Table 3), confirming an earlier study in SCLC cell lines and xenografts that had identified LSD1 as a therapeutic target in SCLC [122]. As such, the use of DLL3 as a biomarker may allow the stratification of patients into trials involving LSD1/NOTCH inhibitors moving forward (Table 3).
Reassessing the role of chemoimmunotherapy in chronic lymphocytic leukemia
Published in Expert Review of Hematology, 2020
Yasir Khan, Yung Lyou, Monica El-Masry, Susan O’Brien
In the phase 3 illuminate trial, Moreno et al. compared the efficacy of ibrutinib plus obinutuzumab with chlorambucil plus obinutuzumab [44]. Patients with previously untreated CLL or small lymphocytic lymphoma received ibrutinib plus obinutuzumab (oral ibrutinib 420 mg once daily) or chlorambucil plus obinutuzumab [44]. The primary endpoint was progression-free survival. After a median follow-up of 31.3 months (IQR 29.4–33.2), median progression-free survival was significantly longer in the ibrutinib plus obinutuzumab group (median not reached [95% CI 33.6-non-estimable]) than in the chlorambucil plus obinutuzumab group (19.0 months [15.1–22.1]; HR 0.23 [95% CI 0.15–0.37; p < 0 · 0001]) [44]. The estimated 30-month progression-free survival was 79% (95% CI 70–85) in the ibrutinib plus obinutuzumab group and 31% (23–40) in the chlorambucil plus obinutuzumab group [44]. The most common grade 3 or 4 adverse events in both groups were neutropenia and thrombocytopenia. Serious adverse events occurred in 65 (58%) of 113 patients treated with ibrutinib plus obinutuzumab and 40 (35%) of 115 patients treated with chlorambucil plus obinutuzumab. Treatment-related deaths were reported in one (1%) of 113 patients in the ibrutinib plus obinutuzumab group (sudden death) and one (1%) of 115 patients in the chlorambucil plus obinutuzumab group (neuroendocrine carcinoma of the skin) [44].