Abstract 2095: A phase 2 study of Amuvatinib (MP-470), the first RAD51 inhibitor in combination with platinum-etoposide (PE) in refractory or relapsed small cell lung cancer (ESCAPE).

Byers, Lauren A.; Horn, Leora; Gandhi, Jitendra G.; Kloecker, Goetz; Owonikoko, Taofeek K.; Waqar, Saiama N.; Krzakowski, Maciej; Choy, Gavin; Cecchettini, Nancy; Taverna, Pietro; Sahai, Amarpal; Noursalehi, Mojtaba; Azab, Mohammad; Camidge, D. Ross

doi:10.1158/1538-7445.am2013-2095

Cited by 3 publications

(2 citation statements)

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“…This prompted a phase 2 study in resistant relapsed SCLC with patients receiving amuvatinib in combination with carboplatin and etoposide (ESCAPE; TrEatment of Small Cell lung cancer with Amuvatinib in combination with Platinum Etoposide). A clinical benefit rate of 22% was reported which failed to meet the predefined study endpoint [88].…”

Section: Amuvatinibmentioning

confidence: 99%

Targeting DNA damage in SCLC

et al. 2017

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A B S T R A C TSCLC accounts for 15% of lung cancer worldwide. Characterised by early dissemination and rapid development of chemo-resistant disease, less than 5% of patients survive 5 years. Despite 3 decades of clinical trials there has been no change to the standard platinum and etoposide regimen for first line treatment developed in the 1970's.The exceptionally high number of genomic aberrations observed in SCLC combined with the characteristic rapid cellular proliferation results in accumulation of DNA damage and genomic instability. To flourish in this precarious genomic context, SCLC cells are reliant on functional DNA damage repair pathways and cell cycle checkpoints.Current cytotoxic drugs and radiotherapy treatments for SCLC have long been known to act by induction of DNA damage and the response of cancer cells to such damage determines treatment efficacy. Recent years have witnessed improved understanding of strategies to exploit DNA damage and repair mechanisms in order to increase treatment efficacy.This review will summarise the rationale to target DNA damage response in SCLC, the progress made in evaluating novel DDR inhibitors and highlight various ongoing challenges for their clinical development in this disease.

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Section: Amuvatinibmentioning

confidence: 99%

Targeting DNA damage in SCLC

et al. 2017

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“…Two patients achieved partial response while 3 patients had durable disease control. 95 E2511, a randomized phase II study and several other clinical studies evaluating PARP enzyme inhibitors in SCLC are currently ongoing (NCT01642251; NCT01638546; NCT01286987).…”

Section: Targets and Novel Biologic Therapiesmentioning

confidence: 99%

Small Cell Lung Cancer: Therapies and Targets

Pillai

Owonikoko

2014

Seminars in Oncology

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Small cell lung cancer (SCLC) remains a very fatal disease due to limited therapeutic options. Systemic chemotherapy is the bedrock of treatment for both the limited and extensive stages of the disease. However, the established management paradigm of platinum-based chemotherapy has reached an efficacy plateau. A modest survival improvement, approximately 5%, was witnessed with the addition of cranial or thoracic radiation to systemic chemotherapy. Other strategies to improve outcome of platinum-based chemotherapy in the last 2 decades have met with minimal success. The substitution of irinotecan for etoposide in the frontline treatment of SCLC achieved significant efficacy benefit in Japanese patients but similar benefit could not be reproduced in other patient populations. Salvage treatment for recurrent or progressive SCLC is particularly challenging where topotecan remains the only agent with regulatory approval to date. Ongoing evaluation of biologic agents targeting angiogenesis, sonic hedgehog pathway, DNA repair pathway and immune checkpoint modulators hold some promise for improved outcome in this fatal disease. It is hoped that the coming decade will witness the application of new molecular biology and genomic research techniques to improve our understanding of SCLC biology and identification of molecular subsets that can be targeted appropriately using established and emerging biological agents similar to the accomplishments of the last decade with non small cell lung cancer.

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