Phase IB study to evaluate efficacy and tolerability of olaparib (AZD2281) plus gefitinib in patients (P) with epidermal growth factor receptor (EGFR) mutation positive advanced non-small cell lung cancer (NSCLC) (NCT=1513174/GECP-GOAL).

Campelo, Rosario García; Felip, Enriqueta; Massutí, Bartomeu; Majem, Margarita; Costa, Enric Carcereny; Palmero, R.; Molina-Vila, Miguel Ángel; Martı́nez, Pablo; Martí-Ciriquián, Juan Luis; Curbera, Guillermo Alonso-Jáudenes; Pallarès, Cinta; Cardenal, Felipe; Gonzalez-Arenas, Maria Carmen; Casas, Clara Mayo-de las; Sanchez-Ronco, María; Rosell, Rafael

doi:10.1200/jco.2014.32.15_suppl.8079

Cited by 7 publications

(8 citation statements)

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“…That brought the idea of testing olaparib, an inhibitor of poly ADP ribose polymerase (PARP) that can down-regulate BRCA1 expression, in combination with EGFR TKI therapy as first-line treatment in EGFR-mutant advanced lung cancer patients. The results from Phase IB GOAL trial was presented in 2013 ASCO meeting, which confirmed the activity and tolerability of the combination [73]. Multicenter Phase II study opened up in July 2013 in Spain and patient recruitment is still ongoing (NCT01513174).…”

Section: Poly Adp-ribose Polymerase Inhibitormentioning

confidence: 85%

Emerging treatment for advanced lung cancer withEGFRmutation

Inal

Yilmaz

Piperdi

et al. 2015

Expert Opinion on Emerging Drugs

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It is essential to uncover the complex mechanisms underlying the progression of lung cancer after upfront EGFR TKIs. Next generation, in particular, the third generations of EGFR TKIs have been developed against acquired T790M mutation with promising clinical activity and better toxicity profile. Combination of targeted therapies has also been explored. Further studies are needed to detect the real-time changes of the resistance mechanisms and to develop new therapeutic strategies for lung cancer patients with EGFR mutations.

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Section: Poly Adp-ribose Polymerase Inhibitormentioning

confidence: 85%

Emerging treatment for advanced lung cancer withEGFRmutation

Inal

Yilmaz

Piperdi

et al. 2015

Expert Opinion on Emerging Drugs

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“…For example, an EGFR inhibitor combination has been explored following clinical data from the EURTAC trial showing that low BRCA1 mRNA levels were associated with longer PFS to erlotinib (Tarceva; Genentech) (130). A phase I trial of olaparib with gefitinib (Iressa; AstraZeneca) demonstrated safety and tolerability, as well as promising signals of antitumor activity (131); a phase 2 trial is now accruing (132). Recent pre-clinical data also suggest that inhibition of the receptor tyrosine kinase c-MET hypersensitises cells to PARP inhibition and the clinical evaluation of this finding is likely to follow (133).…”

Section: Combination Strategiesmentioning

confidence: 99%

Targeting DNA Repair in Cancer: Beyond PARP Inhibitors

et al. 2017

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Germline aberrations in critical DNA repair and DNA-damage response (DDR) genes cause cancer predisposition, while various tumors harbor somatic mutations causing defective DDR/DNA repair. The concept of synthetic lethality can be exploited in such malignancies, as exemplified by approval of poly(ADP-ribose) polymerase inhibitors for treating BRCA1/2 mutated ovarian cancers. Herein, we detail how cellular DDR processes engage various proteins that sense DNA damage, initiate signaling pathways to promote cell cycle checkpoint activation, trigger apoptosis and coordinate DNA repair. We focus on novel therapeutic strategies targeting promising DDR targets and discuss challenges of patient selection and the development of rational drug combinations.

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“…The role of PARPi in patients with EGFR mutant NSCLC has been studied in a phase IB study of olaparib and the EGFR tyrosine kinase inhibitor (TKI) gefitinib (127). It was noted that high BRCA1 mRNA expression is associated with a shorter PFS in EGFR-mutated patients treated with erlotinib.…”

Section: Trials With Parpi In Gbrcam And/or Brca-like Advanced Solid mentioning

confidence: 99%

Beyond Breast and Ovarian Cancers: PARP Inhibitors for BRCA Mutation-Associated and BRCA-Like Solid Tumors

et al. 2014

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Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown clinical activity in patients with germline BRCA1/2 mutation (gBRCAm)-associated breast and ovarian cancers. Accumulating evidence suggests that PARPi may have a wider application in the treatment of cancers defective in DNA damage repair pathways, such as prostate, lung, endometrial, and pancreatic cancers. Several PARPi are currently in phase I/II clinical investigation, as single-agents and/or combination therapy in these solid tumors. Understanding more about the molecular abnormalities involved in BRCA-like phenotype in solid tumors beyond breast and ovarian cancers, exploring novel therapeutic trial strategies and drug combinations, and defining potential predictive biomarkers are critical to expanding the scope of PARPi therapy. This will improve clinical outcome in advanced solid tumors. Here, we briefly review the preclinical data and clinical development of PARPi, and discuss its future development in solid tumors beyond gBRCAm-associated breast and ovarian cancers.

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Phase IB study to evaluate efficacy and tolerability of olaparib (AZD2281) plus gefitinib in patients (P) with epidermal growth factor receptor (EGFR) mutation positive advanced non-small cell lung cancer (NSCLC) (NCT=1513174/GECP-GOAL).

Cited by 7 publications

References 0 publications

Emerging treatment for advanced lung cancer withEGFRmutation

Emerging treatment for advanced lung cancer withEGFRmutation

Targeting DNA Repair in Cancer: Beyond PARP Inhibitors

Beyond Breast and Ovarian Cancers: PARP Inhibitors for BRCA Mutation-Associated and BRCA-Like Solid Tumors

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