Clinical trial NCT05421936: Osimertinib for NSCLC With Uncommon EGFR Mutations
Official title: Uncommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-life Practice in First Line Setting
Study type: OBSERVATIONAL
Overall status: SUSPENDED
Conditions: Carcinoma, Non-Small-Cell Lung
Genes, erbB-1
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: AstraZeneca
First posted: 2022-06-16
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Advanced NSCLC with uncommon EGFR mutation

Brief summary: This is a multi-center, retrospective study of ucEGFRmut (exon 20 insertions excluded) metastatic NSCLC osimertinib-treated as first EGFR inhibitor. RECIST and RANO-BM brain objective response rate (ORR) were evaluated by investigators. mPFS, mOS and mDOR were calculated from osimertinib initiation. Mutations found at resistance were collected.

Detailed description: The epidermal growth factor receptor ( EGFR) is the most common targetable driver in non-small cell lung cancer (NSCLC). Approximately 90% of the EGFR mutations include an exon 19 deletion and a L858R point mutation at exon 21. Less common mutations include, among others, G719X in exon 18, L861Q in exon 21, exon 20 insertions, S768I in exon 20, and T790M in exon 20. Osimertinib is an EGFR TKI that has been developed as non-competitive inhibitor targeting a range of EGFR mutant molecules, currently regarded as the first-line treatment of choice to EGFR mutant (EGFRm) patients. Inhibition of the less common EGFR mutant by osimertinib has been demonstrated.

Real-world data showed lower response rate (RR) and progression free survival (PFS) in patients harboring uncommon EGFR mutations compared to the ones with common mutations treated with EGFR TKIs. Osimertinib as treatment for patients with rare mutations has been assessed in a single arm phase II study in Korea. RR was 50%, PFS was 8.2 months, mOS was not reached. Osimertinib activity in patients with uncommon mutations was assessed also in a retrospective US study, time on treatment ranged from 7.7 months to 19.3 months.

This is a multi-centric, retrospective, real-world study. Study goal is to collect high quality data regarding the efficacy of osimertinib in TKI naive NSCLC patients with uncommon EGFR mutations. The primary endpoints are progression-free survival and overall survival, from osimertinib start. Secondary endpoints would be RECIST response, adverse events, time on treatment and time to CNS progression, CNS response and mechanisms of resistance if tested.

The study includes researchers from Belgium, Denmark, Israel, Switzerland, Netherlands, Germany, France, Italy and USA. Data collection will be conducted at each participating site, following ethics approval. No patient identifying information will leave each of the participating centers. Data will be collected centrally by the lead investigators and analyzed for the entire study cohort and for subgroups if deemed appropriate.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years
2. NSCLC by histologic or cytologic diagnosis
3. Stage IV or stage III not amendable to curative treatment (i.e., advanced disease)
4. Uncommon mutation of EGFR (exon 20 insertion excluded)
5. Treated with osimertinib for advanced disease as first TKI
6. Osimertinib initiated not later than end of January 2021

Exclusion criteria:

1. Lack of any follow-up data
2. Lack of consent for data collection or ethics committee approval for the waiver of informed consent (i.e. for deceased patients)

Primary outcomes:
measure: Progression free survival
timeFrame: From date of osimertinib initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
measure: Overall survival
timeFrame: From date of osimertinib initiation until date of death from any cause, assessed up to 100 months
Secondary outcomes:
measure: Overall response rate
timeFrame: From date of osimertinib initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
measure: Brain response
timeFrame: From date of osimertinib initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
measure: Adverse events on osimertinib
timeFrame: From date of osimertinib initiation until 30 days after the date of last osimertinib treatment or date of death from any cause, whichever came first, assessed up to 100 months
measure: Time on treatment (TOT, on osimertinib)
timeFrame: From date of osimertinib initiation until the date of last osimertinib treatment or date of death from any cause, whichever came first, assessed up to 100 months
measure: Time to CNS progression
timeFrame: From date of osimertinib initiation until the date of first documented CNS progression or censured at last follow up or at date of death from any cause, whichever came first, assessed up to 100 months
measure: Mechanisms of resistance
timeFrame: From date of osimertinib initiation until the date of molecular test performed after any documented progression, assessed up to 100 months
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: Sheba Medical Centre
Study officials:
affiliation: Sheba Medical Center, Ramat Gan, Israel
name: Jair Bar, MD-PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Geneva University Hospital, Geneva, Switzerland
name: Alfredo Addeo, MD
role: PRINCIPAL_INVESTIGATOR
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