scholarly journals Partial Response to Platinum Doublets in Refractory EGFR-Positive Non-Small Cell Lung Cancer Patients after RRx-001: Evidence of Episensitization

2016 ◽  
Vol 9 (1) ◽  
pp. 62-67 ◽  
Author(s):  
Corey A. Carter ◽  
Bryan T. Oronsky ◽  
Scott Z. Caroen ◽  
Jan J. Scicinski ◽  
Pedro Cabrales ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Partial Response ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Egfr Mutated

RRx-001, an experimental systemically non-toxic epi-immunotherapeutic agent, which potentiates the resensitization of resistant cancer cells to formerly effective therapies, is under active investigation in several clinical trials that are based on sequential or concomitant rechallenge to resistant first- or second-line regimens. One of these trials is designated TRIPLE THREAT (NCT02489903), because it explores the conditioning or priming effect of RRx-001 on three tumor types - non-small cell lung cancer (NSCLC), small cell lung cancer and high-grade neuroendocrine tumors - prior to re-administration of platinum doublets. In follow-up to a recent case study, which describes early monotherapeutic benefit with RRx-001 in a refractory EGFR-mutated NSCLC tumor, we present subsequent evidence of a radiological partial response to reintroduced platinum doublets after RRx-001. For the 50% of patients with EGFR-mutated NSCLC who progress on EGFR-tyrosine kinase inhibitors (without evidence of a T790M mutations) as well as platinum doublets and pemetrexed/taxane, no other clinically established treatment options exist. A retrial of these therapies in EGFR-positive NSCLC patients via priming with epigenetic agents such as RRx-001 constitutes a strategy to ‘episensitize' tumors (i.e. reverse resistance by epigenetic means) and to extend overall survival.

Response with pemrbolizumab in a patient with EGFR mutated non-small cell lung cancer harbouring insertion mutations in V834L and L858R

2021 ◽  
pp. 107815522110578
Author(s):  
Matthew J. Hadfield ◽  
Alla Turshudzhyan ◽  
Khalid Shalaby ◽  
Aswanth Reddy
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Durable Response ◽  
Egfr Mutated

Introduction Lung cancer is the leading cause of cancer-related deaths with non-small cell lung cancer (NSCLC) being the most common of them. About a third of NSCLC cases have an epidermal growth factor (EGFR) mutation, which is usually susceptible to tyrosine kinase inhibitors (TKIs). In rare cases where patients progress through TKI therapy, the use of immune checkpoint inhibitors (ICIs) remains controversial. Case report We describe a case of a patient with significant history of smoking and EGFR mutated programmed death ligand-1 (PD-L1) positive NSCLC who was initially treated with TKI therapy. Management/Outcome While patient progressed on TKI therapy, he was able to achieve a durable response with a single PD-L1 agent, pembrolizumab. Contrary to the available evidence, the presented EGFR mutant NSCLC responded to PD-L1 pathway inhibition. Discussion From our observation Pembrolizumab could be promising in patients with rare EGFR mutations who do not respond to EGFR directed therapy. Our report provides supporting data for the use of immunotherapies in patients with EGFR mutated NSCLC.

scholarly journals Clinical case of use of osimertinib in a patient with disseminated EGFR-mutated non-small cell lung cancer in the first-line therapy

2020 ◽  
pp. 194-198
Author(s):  
K. A. Sarantseva ◽  
K. K. Laktionov ◽  
E. V. Reutova ◽  
D. I. Yudin ◽  
V. V. Breder
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cns Metastases ◽  
Epidermal Growth ◽  
Egfr Mutated

Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) that has been approved for the treatment of metastatic non-small cell lung cancer (NSCLC) positive for the secondary T790M mutation of EGFR. Central nervous system (CNS) metastases are a common complication in patients with epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancer (NSCLC), resulting in a poor prognosis and limited treatment options. Almost 25% of patients present with accompanying central nervous system (CNS) metastases at the first diagnosis. Treatment of CNS metastases requires a multidisciplinary approach, and the optimal treatment options and sequence of therapies are yet to be established. Many systemic therapies have poor efficacy in the CNS due to the challenges of crossing the blood‐brain barrier (BBB), creating a major unmet need for the development of agents with good BBB‐penetrating biopharmaceutical properties. Although the CNS penetration of first‐ and second‐generation EGFR tyrosine kinase inhibitors (TKIs) is generally low, EGFR‐TKI treatment has been shown to delay time to CNS progression in patients with both in preventing or delaying the onset of CNS metastases, and in leading to intracranial response of preexisting CNS lesions. This is one of the arguments in favor of starting osimertinib upfront rather than initiating treatment with firstor second-generation EGFR-TKIs.

scholarly journals Efficacy of Paclitaxel plus TS1 against previously treated EGFR mutated non-small cell lung cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7767
Author(s):  
Yen-Han Tseng ◽  
Jen-Fu Shih ◽  
Heng-Sheng Chao ◽  
Yuh-Min Chen
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Treatment Options ◽  
Small Cell ◽  
Wild Type ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Line Chemotherapy

Background Later line chemotherapy (≥2nd lines) such as Docetaxel or immunotherapy is frequently used. As the life expectancy of lung cancer patients is getting longer, we need to provide more treatment options. Other treatment options are not well documented except for Doxetaxel and immunotherapy. Therefore, the efficacy of paclitaxel plus TS1 (TTS1) is warranted. Methods We retrospectively reviewed the chart records of our non-small cell lung cancer patients who were treated between 2010 and 2013. Clinical characteristics, type of tumor, EGFR mutation status, and treatment response to first-line EGFR-TKI therapy and efficacy of TTS1, were collected. Results Twenty eight patients were enrolled in this study. No patients archived complete response and seven patients had partial response (ORR: 25%). The disease control rate was 60.7% (17/28). The progression free survival (PFS) was 4.0 months and overall survival (OS) was 15.8 months. Of them, 17 had EGFR mutations, eight EGFR wild type, and three were unknown EGFR status. After TTS1 treatment, patients with EGFR mutations had better PFS (4.9 months vs. 1.8 months) and OS (15.5 months vs. 7.2 months) compared with those of EGFR wild type. Conclusions TTS1 are effective later line chemotherapy, especially in tumor EGFR mutated patients. Paclitaxel plus TS1 is another treatment of choice for NSCLC patients before a more effective treatment strategy is found.

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