scholarly journals A Partial Response to Reintroduced Chemotherapy in a Resistant Small Cell Lung Cancer Patient after Priming with RRx-001

2016 ◽  
Vol 10 ◽  
pp. CMO.S40429 ◽  
Author(s):  
Bryan Oronsky ◽  
Scott Caroen ◽  
Karen Zeman ◽  
Mary Quinn ◽  
Christina Brzezniak ◽  
...  

As an exceedingly recalcitrant and highly aggressive tumor type without Food and Drug Administration-approved treatment or a known cure, the prognosis of recurrent extensive stage platinum-resistant/refractory small cell lung cancer (SCLC) is worse than other types of lung cancer, and many other tumor types, given a response rate of less than 10% and an overall survival of less than six months. It was broadly classified into three groups based on the initial response to cisplatin/etoposide therapy, platinum-refractory, platinum-resistant, and platinum-sensitive, extensive stage SCLC inevitably relapses, at which point the only standard options are to rechallenge with the first-line chemotherapeutic regimen in the case of sensitive disease or to start the topoisomerase I inhibitor, topotecan. Sensitive disease is defined by a response to the first-line therapy and a treatment-free interval of at least 90 days, while the definitions of refractory and resistant disease, respectively, are nonresponse to the first-line treatment or relapse within 90 days. As an important predictor of response to the second-line treatment, the clinical cutoff of three months (or two months in some cases) for resistant and sensitive disease, which along with performance status prognostically separates patients into high- and low-risk categories, dictates subsequent management. This case report presents a resistant SCLC patient enrolled on a Phase II clinical trial called QUADRUPLE THREAT (formerly TRIPLE THREAT, NCT02489903) who responded to reintroduced platinum doublets after sequential priming with the resistance-reversing epi-immunotherapeutic agent, RRx-001. In the QUADRUPLE THREAT clinical trial, both during priming with RRx-001 and during sequential treatment with platinum doublets, the patient maintained a good quality of life and performance status.

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Bi-Cheng Wang ◽  
Bo-Ya Xiao ◽  
Peng-Cheng Li ◽  
Bo-Hua Kuang ◽  
Wang-Bing Chen ◽  
...  

Background. The prognosis of patients with extensive-stage small cell lung cancer (SCLC) is poor. Adding an immune checkpoint inhibitor (ICI) to chemotherapy may exert a synergistic effect and improve survival outcomes. However, for treatment-naive extensive-stage SCLC patients, the efficacy of immunotherapy in combination with cytotoxic chemotherapy remains controversial. Objective. To evaluate the benefits and risks of the combination of immunotherapy and chemotherapy and to assess the comparative effectiveness of different first-line treatment strategies for extensive-stage SCLC. Methods. PubMed, Web of Science, EMBASE, and Cochrane Library were searched for randomized clinical trials studying different immunotherapeutics for patients with previously untreated extensive-stage SCLC up to Feb 16, 2020. The primary outcomes were overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were objective response rate (ORR), disease control rate (DCR), and adverse events. Results. We identified 141 published records, and 4 studies (comprising 2202 patients) were included in the analysis. Immunotherapy (including ipilimumab, atezolizumab, and durvalumab) plus chemotherapy was associated with better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75–0.93; risk ratio (RR) 0.90, 95% CI 0.81–1.00) and PFS (HR: 0.81, 95% CI 0.74–0.88; RR 0.96, 95% CI 0.93–0.99) than placebo plus chemotherapy. The addition of immunotherapy to chemotherapy showed similar improvement in ORR, DCR, and adverse events versus placebo plus chemotherapy. On the surface under the cumulative ranking (SUCRA) analysis, the anti-PD-L1 agent, atezolizumab, had the highest likelihood of achieving improved OS (93.4%) and PFS (95.0%). Conclusion. In the first-line setting, combining immunotherapy with chemotherapy is better than standard chemotherapy in terms of OS and PFS. Across the eligible studies, PD-L1 inhibitors might be preferred. Further explorations of more ICIs in the first-line treatment for extensive-stage SCLC patients should be needed.


Immunotherapy ◽  
2021 ◽  
Author(s):  
Ching-Yi Chen ◽  
Wang-Chun Chen ◽  
Chao-Ming Hung ◽  
Yu-Feng Wei

This meta-analysis investigated the clinical benefits of chemo-immunotherapy in extensive-stage small-cell lung cancer (ES-SCLC). Seven randomized controlled trials with a total of 2862 patients were analyzed. Compared with chemotherapy alone, chemo-immunotherapy provided a better progression-free survival (PFS) with a hazard ratio (HR) of 0.81, p < 0.00001, and overall survival (OS) with a HR of 0.82, p < 0.0001; however, the incidence of treatment-related adverse effects (TRAEs) was significantly increased. Subgroup analyses showed that good performance status, cisplatin-based chemotherapy, without brain metastases at baseline and non-Asian populations were associated with greater benefits in OS from chemo-immunotherapy. Chemo-immunotherapy demonstrated better PFS and OS compared with chemotherapy alone as first line treatment in ES-SCLC, but additional TRAEs should be closely monitored.


Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 890
Author(s):  
Rocío Jiménez Jiménez Galán ◽  
Elena Prado-Mel ◽  
María Antonia Pérez-Moreno ◽  
Estefanía Caballano-Infantes ◽  
Sandra Flores Moreno

The KEYNOTE-024 clinical trial showed promising results for pembrolizumab in the first-line of treatment of advanced non-small-cell lung cancer (NSCLC). However, the profile of patients in real-world practice differs from those included in this clinical trial. Here, an observational single-center retrospective study was performed through a comparative analysis of clinical outcomes after pembrolizumab therapy according to the Eastern Cooperative Oncology Group Stage Performance Status (ECOG PS). Moreover, univariate and multivariate analyses were carried out to detect prognostic factors. In our cohort, 63.7% of patients had an ECOG PS of 0–1. Regarding response rate, 31.8% of patients had a partial response (PR), 19.3% had stable disease (SD) and 23.9% had progression disease. On the other hand, patients with ECOG PS ≥ 2 showed a significantly lower rate of PR and SD to pembrolizumab than patients with a PS of 0–1. The rate of response, median overall survival (OS) and progression-free survival (PFS) were significantly higher in patients with ECOG PS 0–1 than in those with ECOG PS ≥ 2. In the current study, we found ECOG PS as the only independent predictor of OS and PFS. Due to the ECOG PS scale being a subjective parameter, other tools are needed to identify treatment effectiveness to each patient.


Lung Cancer ◽  
2003 ◽  
Vol 41 ◽  
pp. S232-S233
Author(s):  
Kaoru Matsui ◽  
Yuichiro Ohe ◽  
Shunichi Negoro ◽  
Kazuhiko Nakagawa ◽  
Takahiko Sugiura ◽  
...  

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