Upfront Therapy for Myeloma: Tailoring Therapy across the Disease Spectrum

Author(s):  
S. Vincent Rajkumar

Overview: The treatment of multiple myeloma is evolving rapidly. Despite the number of regimens and combinations available, there is lack of data from phase III trials demonstrating superiority of one regimen over the other in terms of overall survival and/or quality of life. The only clear survival signals have come from studies that compared newer regimens with historic ones such as melphalan-prednisone (MP) or vincristine-doxorubicin hydrochloride-thalidomide (VAD). Thus, the choice of therapy at present is often made based on physician discretion, bias, and limited data from phase II studies. Further, the regimens available have considerably different profiles in terms of safety, convenience, and cost. Given the dramatic variations in expected outcome depending on the various known prognostic factors, a risk-adapted strategy is required to provide the best available therapy to each patient based on host factors as well as prognostic markers of disease aggressiveness. This article reviews the current status of myeloma therapy and risk stratification. Results from major phase III trials are reviewed, and a risk-adapted individualized approach to therapy is presented and discussed.

Oncology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Kristjan Ukegjini ◽  
Paul Martin Putora ◽  
Marisa Guidi ◽  
Krisztian Süveg ◽  
Nikola Cihoric ◽  
...  

<b><i>Introduction:</i></b> Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a treatment option for patients with peritoneal metastases. We evaluated the current status of ongoing prospective clinical trials investigating PIPAC to provide an overview and predict trends in this field. <b><i>Methods:</i></b> All 367,494 records of clinical trials registered at ClinicalTrials.gov were searched for trials dealing with PIPAC. Active or unpublished trials were further analyzed. <b><i>Results:</i></b> In total, 22 clinical trials were identified and selected for further analyses. Most trials had a single-arm design and were phase I or II. No phase III trials were registered. Academic centers were recorded as primary sponsors in the majority of trials (63.6%). Every year, between 2 and 5 new trials were initiated. In 17 trials (81.8%), PIPAC was used in a palliative setting only, 2 trials performed PIPAC in a neoadjuvant setting, and 2 trials performed PIPAC in an adjuvant setting. Six different drugs (doxorubicin, cisplatin, oxaliplatin, nab-paclitaxel, 5-fluorouracil, and docetaxel) were used in these clinical trials. Most trials investigated the efficacy (<i>n</i> = 15) or safety (<i>n</i> = 7) of PIPAC therapies. <b><i>Conclusions:</i></b> The results of ongoing clinical trials will bring specific information on indications for PIPAC as well as the impact of PIPAC on quality of life and overall survival.


Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 860 ◽  
Author(s):  
Jacob J. Adashek ◽  
Rohit K. Jain ◽  
Jingsong Zhang

The approval of upfront abiraterone for castration-sensitive prostate cancer and the approval of enzalutamide and apalutamide for non-metastatic castration-resistant prostate cancer have led to early utilization of potent androgen receptor (AR) signaling inhibitors in treating advanced prostate cancer. There is an unmet need to develop novel therapies beyond targeting AR signaling for metastatic castration-resistant prostate cancer (mCRPC). Poly (ADP-ribose) polymerase inhibitors (PARPi) belong to a class of targeted agents being developed for the treatment of homologous recombination repair (HRR) deficient tumors. Olaparib, rucaparib, niraparib, veliparib, and talazoparib were evaluated in early phase trials as a monotherapy for HRR-deficient mCRPC. Among them, olaparib and rucaparib have breakthrough designations for BRCA1/2-mutated mCRPC. Phase II studies also reported clinical activity of the PARPi and abiraterone combination and the PARPi checkpoint inhibitor combination in HRR-intact mCRPC. Ongoing phase III trials are testing these combinations as frontline or later line treatments for mCRPC. This review summarizes the critical clinical data as well as ongoing clinical trials for developing PARPi in treating mCRPC.


2018 ◽  
Vol 36 (25) ◽  
pp. 2585-2592 ◽  
Author(s):  
Cesare Gridelli ◽  
Alessandro Morabito ◽  
Luigi Cavanna ◽  
Andrea Luciani ◽  
Paolo Maione ◽  
...  

Purpose To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non–small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4. Patients and Methods Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed α of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of cisplatin on the basis of intention-to-treat and adjusted by trial, histotype, non-platinum companion drug, stage, performance status, sex, age, and size of the study center. Results From March 2011 to August 2016, 531 patients (MILES-3, 299; MILES-4, 232) were assigned to gemcitabine or pemetrexed without (n = 268) or with cisplatin (n = 263). Median age was 75 years, 79% were male, and 70% had nonsquamous histology. At a median 2-year follow-up, 384 deaths and 448 progression-free survival events were recorded. Overall survival was not significantly prolonged with cisplatin (HR, 0.86; 95% CI, 0.70 to 1.05; P = .14) and global health status score of quality of life was not improved, whereas progression-free survival (HR, 0.76; 95% CI, 0.63 to 0.92; P = .005) and objective response rate (15.5% v 8.5%; P = .02) were significantly better. Significantly more severe hematologic toxicity, fatigue, and anorexia were found with cisplatin. Conclusion The addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4126-4126 ◽  
Author(s):  
E. Bria ◽  
P. Carlini ◽  
A. Gelibter ◽  
E. Ruggeri ◽  
A. Ceribelli ◽  
...  

4126 Background: Molecular targeting of pathways that are deregulated in pancreatic cancer is a promising approach aimed at improving the dismal prognosis of APC pts. However, the clinical impact of novel “biological” drugs (ND) remains to be defined. Methods: All prospective phase III trials comparing single-agent Gemcitabine (G) with either a ND or a combination of ND and G (ND+G) were considered eligible. A pooled analysis was performed and event-based relative risk ratios (RR) with 95% CI were derived through both a fixed- and a random-effect model approach, exploring OS as the primary outcome and PFS and ORR as secondary outcomes. Heterogeneity between different trials was also taken into account. Results: Six trials involving 2361 pts were identified; ND tested included: FTI inhibitors (1 trial), MMP inhibitors (3 trials), EGFR inhibitors (1 trial), and anti-gastrin vaccine (1 trial). The analysis was conducted considering three different subgroups: 1) overall population (2361 patients, 6 trials), 2) ND+G vs G (1879 patients, 4 trials), and 3) ND vs G (482 patients, 2 trials). As shown in the table, no significant differences in either the primary outcome (OS) or the secondary outcome of PFS were observed in the overall population as well as in ND+G vs G trials, while a significant negative trend for ND was found in ND vs G trials with regard to both endpoints. Conversely the evaluation of the secondary endpoint of ORR significantly favored G in the overall population as well as in ND vs G trials, while a not significant negative trend for ND was observed in ND+G vs G trials. Conclusions: G remains the treatment of choice in APC pts. The ND tested, either alone or combined with G, do not seem to add any benefit over G. A better understanding of pancreatic cancer biology and further clinical evaluation of new agents and is needed to improve prognosis in APC pts. [Table: see text] No significant financial relationships to disclose.


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