Representativeness of Phase III Trial for Osimertinib in Pretreated Advanced EGFR-Mutated Non-small-cell Lung Cancer Patients and Treatment Outcomes in Clinical Practice

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Overall survival (OS) data of osimertinib in pretreated non-small-cell lung cancer (NSCLC) in real-world practice is limited, and treatment benefits for patients not represented in the pivotal trials (ineligible) are unclear.

Objective

To determine the representativeness of the AURA3 trial for NSCLC patients treated with osimertinib in a real-world setting and to determine outcomes of patients who were represented in the AURA3 trial (eligible) and those who were ineligible.

Methods

Advanced NSCLC patients receiving post first-line osimertinib were included in this retrospective study and were divided into two groups based on eligibility criteria of the AURA3 trial. Progression-free survival (PFS) and OS were estimated using the Kaplan–Meier method. Cox models were used to estimate the association of eligibility criteria with OS.

Results

328 patients were included; 126 (38%) patients were eligible and 202 (62%) patients were ineligible. The most common ineligibility reasons were the number of earlier treatment lines and an Eastern Cooperative Oncology Group performance status (ECOG PS) > 1. PFS of eligible and ineligible patients was not statistically different (8.0 vs. 5.8 months, p = 0.062). Eligible patients had a longer OS (24.0 vs. 15.4 months, p = 0.001) compared to ineligible patients. ECOG PS was the best predictor for OS. An ECOG PS of 1 was already associated with poorer survival compared to an ECOG PS of 0 (hazard ratio 1.54; p = 0.016).

Conclusion

The majority of the study population was not represented in the AURA3 trial. Survival outcomes of eligible patients are in concordance with the AURA3 trial, while OS of ineligible patients was significantly shorter compared to eligible patients.

Related collections

Most cited references 20

Record: found
Abstract: found
Article: not found

Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer

Tony Mok, Yi-Long Wu, Myung-Ju Ahn … (2017)

Background Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is selective for both EGFR-TKI sensitizing and T790M resistance mutations in patients with non-small-cell lung cancer. The efficacy of osimertinib as compared with platinum-based therapy plus pemetrexed in such patients is unknown. Methods In this randomized, international, open-label, phase 3 trial, we assigned 419 patients with T790M-positive advanced non-small-cell lung cancer, who had disease progression after first-line EGFR-TKI therapy, in a 2:1 ratio to receive either oral osimertinib (at a dose of 80 mg once daily) or intravenous pemetrexed (500 mg per square meter of body-surface area) plus either carboplatin (target area under the curve, 5 [AUC5]) or cisplatin (75 mg per square meter) every 3 weeks for up to six cycles; maintenance pemetrexed was allowed. In all the patients, disease had progressed during receipt of first-line EGFR-TKI therapy. The primary end point was investigator-assessed progression-free survival. Results The median duration of progression-free survival was significantly longer with osimertinib than with platinum therapy plus pemetrexed (10.1 months vs. 4.4 months; hazard ratio; 0.30; 95% confidence interval [CI], 0.23 to 0.41; P<0.001). The objective response rate was significantly better with osimertinib (71%; 95% CI, 65 to 76) than with platinum therapy plus pemetrexed (31%; 95% CI, 24 to 40) (odds ratio for objective response, 5.39; 95% CI, 3.47 to 8.48; P<0.001). Among 144 patients with metastases to the central nervous system (CNS), the median duration of progression-free survival was longer among patients receiving osimertinib than among those receiving platinum therapy plus pemetrexed (8.5 months vs. 4.2 months; hazard ratio, 0.32; 95% CI, 0.21 to 0.49). The proportion of patients with adverse events of grade 3 or higher was lower with osimertinib (23%) than with platinum therapy plus pemetrexed (47%). Conclusions Osimertinib had significantly greater efficacy than platinum therapy plus pemetrexed in patients with T790M-positive advanced non-small-cell lung cancer (including those with CNS metastases) in whom disease had progressed during first-line EGFR-TKI therapy. (Funded by AstraZeneca; AURA3 ClinicalTrials.gov number, NCT02151981 .).

0 comments Cited 875 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: not found
Article: not found

A note on quantifying follow-up in studies of failure time.

Michael Schemper, Terry L Smith (1996)

0 comments Cited 442 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Acquired resistance to TKIs in solid tumours: learning from lung cancer.

D. Ross Camidge, William Pao, Lecia V. Sequist (2014)

The use of advanced molecular profiling to direct the use of targeted therapy, such as tyrosine kinase inhibitors (TKIs) for patients with advanced-stage non-small-cell lung cancer (NSCLC), has revolutionized the treatment of this disease. However, acquired resistance, defined as progression after initial benefit, to targeted therapies inevitably occurs. This Review explores breakthroughs in the understanding and treatment of acquired resistance in NSCLC, focusing on EGFR mutant and ALK rearrangement-positive disease, which may be relevant across multiple different solid malignancies with oncogene-addicted subtypes. Mechanisms of acquired resistance may be pharmacological (that is, failure of delivery of the drug to its target) or biological, resulting from evolutionary selection on molecularly diverse tumours. A number of clinical approaches can maintain control of the disease in the acquired resistance setting, including the use of radiation to treat isolated areas of progression and adding or switching to cytotoxic chemotherapy. Furthermore, novel approaches that have already proven successful include the development of second-generation and third-generation inhibitors and the combination of some of these inhibitors with antibodies directed against the same target. With our increased understanding of the spectrum of acquired resistance, major changes in how we conduct clinical research in this setting are now underway.

0 comments Cited 323 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Lishi Lin:

ORCID: http://orcid.org/0000-0002-9733-7720

l.lin@nki.nl

Journal

Journal ID (nlm-ta): Target Oncol

Journal ID (iso-abbrev): Target Oncol

Title: Targeted Oncology

Publisher: Springer International Publishing (Cham )

ISSN (Print): 1776-2596

ISSN (Electronic): 1776-260X

Publication date (Electronic): 11 December 2021

Publication date PMC-release: 11 December 2021

Publication date (Print): 2022

Volume: 17

Issue: 1

Pages: 53-59

Affiliations

[1 ]GRID grid.430814.a, ISNI 0000 0001 0674 1393, Department of Pharmacy and Pharmacology, , The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, ; Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands

[2 ]GRID grid.430814.a, ISNI 0000 0001 0674 1393, Department of Thoracic Oncology, , The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, ; Amsterdam, The Netherlands

[3 ]GRID grid.10419.3d, ISNI 0000000089452978, Department of Pulmonology, , Leiden University Medical Center, ; Leiden, The Netherlands

[4 ]GRID grid.5477.1, ISNI 0000000120346234, Department of Pharmaceutical Sciences, , Utrecht University, ; Utrecht, The Netherlands

[5 ]GRID grid.487647.e, Department of Pharmacology, , Princess Máxima Center for Pediatric Oncology, ; Utrecht, The Netherlands

[6 ]GRID grid.5477.1, ISNI 0000000120346234, Department of Clinical Pharmacy, University Medical Center Utrecht, , Utrecht University, ; Utrecht, The Netherlands

Author information

Lishi Lin http://orcid.org/0000-0002-9733-7720

Article

Publisher ID: 862

DOI: 10.1007/s11523-021-00862-x

PMC ID: 8783869

PubMed ID: 34894319

SO-VID: da2fba8b-f895-4a41-b80c-8fc34b63a9de

License:

Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

History

Date accepted : 27 November 2021

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Comments

Comment on this article

scite_

Representativeness of Phase III Trial for Osimertinib in Pretreated Advanced EGFR-Mutated Non-small-cell Lung Cancer Patients and Treatment Outcomes in Clinical Practice

Read this article at

Abstract

Background

Objective

Methods

Results

Conclusion

Related collections

Karger: Oncology

Most cited references 20

Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer

A note on quantifying follow-up in studies of failure time.

Acquired resistance to TKIs in solid tumours: learning from lung cancer.

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Categories

Custom metadata

Comments

Comment on this article

Similar content 826