Combination of gefitinib and olaparib versus gefitinib alone in EGFR mutant non-small-cell lung cancer (NSCLC): A multicenter, randomized phase II study (GOAL)

García‐Campelo, Rosario; Arrieta, Óscar; Massutí, Bartomeu; Rodríguez-Abreu, Delvys; Granados, A.L. Ortega; Majem, Margarita; Vicente, David; Lianes, P.; Bosch-Barrera, Joaquim; Insa, Amelia; Dómine, Manuel; Reguart, Noemı́; Guirado, M.; Sala, María; Vázquez‐Estévez, Sergio; Bernabé, R.; Drozdowskyj, Ana; Verdu, Ana; Karachaliou, Niki; Molina-Vila, Miguel Ángel; Rosell, Rafael

doi:10.1016/j.lungcan.2020.09.018

Cited by 20 publications

(29 citation statements)

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“… 4 In the phase 2B part of the GOAL study, between July 2013 and July 2016, a total of 186 patients with previously untreated metastatic EGFR -mutant NSCLC were included in 34 centers in Spain and one in Mexico. 5 The intent-to-treat (ITT) analysis included 91 patients with EGFR -mutant NSCLC in the gefitinib arm and 91 patients with EGFR -mutant NSCLC in the gefitinib plus olaparib arm. 5 Progression-free survival (PFS) and overall survival (OS) were evaluated at the final data cutoff point on July 2017.…”

Section: Introductionmentioning

confidence: 99%

“… 5 The intent-to-treat (ITT) analysis included 91 patients with EGFR -mutant NSCLC in the gefitinib arm and 91 patients with EGFR -mutant NSCLC in the gefitinib plus olaparib arm. 5 Progression-free survival (PFS) and overall survival (OS) were evaluated at the final data cutoff point on July 2017. The median follow-up time was 26.2 months (95% confidence interval [CI]: 20.3–27.8) for gefitinib and 21.2 months (95% CI: 17.5–28.3) for gefitinib plus olaparib ( p = 0.2858).…”

Section: Introductionmentioning

confidence: 99%

“…The median follow-up time was 26.2 months (95% confidence interval [CI]: 20.3–27.8) for gefitinib and 21.2 months (95% CI: 17.5–28.3) for gefitinib plus olaparib ( p = 0.2858). 5 …”

Section: Introductionmentioning

confidence: 99%

“…The primary end point of the phase 2B GOAL study, which was to determine whether the addition of olaparib to gefitinib improved PFS in previously untreated patients with metastatic EGFR -mutant NSCLC, was not met. 5 Median PFS was 10.9 months (95% CI: 9.3–13.3) for gefitinib versus 12.8 months (95% CI: 9.1–14.7) for gefitinib plus olaparib ( p = 0.1242; hazard ratio [HR] = 0.75, 95% CI: 0.52–1.08). 5 Among 174 patients assessable for response, the objective response rate was 68% in the gefitinib arm versus 71% in the gefitinib plus olaparib arm ( p = 0.4873).…”

Section: Introductionmentioning

confidence: 99%

“… 5 Median PFS was 10.9 months (95% CI: 9.3–13.3) for gefitinib versus 12.8 months (95% CI: 9.1–14.7) for gefitinib plus olaparib ( p = 0.1242; hazard ratio [HR] = 0.75, 95% CI: 0.52–1.08). 5 Among 174 patients assessable for response, the objective response rate was 68% in the gefitinib arm versus 71% in the gefitinib plus olaparib arm ( p = 0.4873). 5 No statistically significant differences were found between the two treatment arms in median OS.…”

Section: Introductionmentioning

confidence: 99%

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BRCA1 Expression and Outcome in Patients With EGFR-Mutant NSCLC Treated With Gefitinib Alone or in Combination With Olaparib

Karachaliou

Arrieta

Giménez‐Capitán

et al. 2021

JTO Clinical and Research Reports

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Introduction: DNA repair capacity, as exemplified by BRCA1 gene expression, is related with outcome to EGFR tyrosine kinase inhibitors in patients with EGFR-mutant NSCLC. Olaparib, a PARP inhibitor, reduces BRCA1 expression. Olaparib was tested in combination with gefitinib versus gefitinib single agent, as a first-line therapy for patients with EGFR-mutant NSCLC in the GOAL study (trial registration: NCT01513174). Here, we report the results of the biomarker-related prespecified secondary objectives of the GOAL study. Methods: We evaluated the impact of BRCA1 mRNA expression in 91 patients with EGFR-mutant NSCLC. Of those 91 patients, 51 were randomized to treatment with gefitinib and 40 were randomized to treatment with gefitinib plus olaparib. We explored in vitro whether BRCA1 mRNA levels are related with outcome to gefitinib plus olaparib. The expression levels of 53BP1, CtIP, and AXL were also explored and correlated with the treatment outcome. Results: Overall, as what happened in the GOAL study, no statistically significant difference was observed in median progression-free survival (PFS) between the two treatment arms, for the 91 patients of the present study (p ¼ 0.2419). For patients with high BRCA1 mRNA expression (BRCA1high group), median PFS was 12.9 months in the gefitinib plus olaparib arm, compared with 9.2 months in the gefitinib arm (p ¼ 0.0449). In the gefitinib arm, median PFS was 9.1 months for the BRCA1-high group and 10.2 months for the BRCA1-low group (p ¼ 0.0193). We observed a more pronounced synergism of gefitinib plus olaparib in cells with higher BRCA1 compared with those with low BRCA1 mRNA expression. Conclusions: High BRCA1 mRNA expression identified patients with NSCLC who benefited from gefitinib plus olaparib in the GOAL phase 2 clinical trial.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…The median follow-up time was 26.2 months (95% confidence interval [CI]: 20.3–27.8) for gefitinib and 21.2 months (95% CI: 17.5–28.3) for gefitinib plus olaparib ( p = 0.2858). 5 …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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BRCA1 Expression and Outcome in Patients With EGFR-Mutant NSCLC Treated With Gefitinib Alone or in Combination With Olaparib

Karachaliou

Arrieta

Giménez‐Capitán

et al. 2021

JTO Clinical and Research Reports

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Effect of Metformin Plus Tyrosine Kinase Inhibitors Compared With Tyrosine Kinase Inhibitors Alone in Patients With Epidermal Growth Factor Receptor–Mutated Lung Adenocarcinoma

et al. 2019

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IMPORTANCE Metformin hydrochloride is emerging as a repurposed anticancer drug. Preclinical and retrospective studies have shown that it improves outcomes across a wide variety of neoplasms, including lung cancer. Particularly, evidence is accumulating regarding the synergistic association between metformin and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). OBJECTIVE To assess the progression-free survival (PFS) in patients with advanced lung adenocarcinoma who received treatment with EGFR-TKIs plus metformin compared with those who received EGFR-TKIs alone. DESIGN, SETTING, AND PARTICIPANTS Open-label, randomized, phase 2 trial conducted at the Instituto Nacional de Cancerología (INCan), Mexico City, Mexico. Eligible patients were 18 years or older, had histologically confirmed stage IIIB-IV lung adenocarcinoma with an activating EGFR mutation. INTERVENTIONS Patients were randomly allocated to receive EGFR-TKIs (erlotinib hydrochloride, afatinib dimaleate, or gefitinib at standard dosage) plus metformin hydrochloride (500 mg twice a day) or EGFR-TKIs alone. Treatment was continued until occurrence of intolerable toxic effects or withdrawal of consent. MAIN OUTCOMES AND MEASURES The primary outcome was PFS in the intent-to-treat population. Secondary outcomes included objective response rate, disease control rate, overall survival (OS), and safety.

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Targeting the DNA damage response: PARP inhibitors and new perspectives in the landscape of cancer treatment

Genta

Martorana

Stathis

et al. 2021

Critical Reviews in Oncology/Hematology

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Combination of gefitinib and olaparib versus gefitinib alone in EGFR mutant non-small-cell lung cancer (NSCLC): A multicenter, randomized phase II study (GOAL)

Cited by 20 publications

References 29 publications

BRCA1 Expression and Outcome in Patients With EGFR-Mutant NSCLC Treated With Gefitinib Alone or in Combination With Olaparib

BRCA1 Expression and Outcome in Patients With EGFR-Mutant NSCLC Treated With Gefitinib Alone or in Combination With Olaparib

Effect of Metformin Plus Tyrosine Kinase Inhibitors Compared With Tyrosine Kinase Inhibitors Alone in Patients With Epidermal Growth Factor Receptor–Mutated Lung Adenocarcinoma

Targeting the DNA damage response: PARP inhibitors and new perspectives in the landscape of cancer treatment

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