Therapeutic efficacy of Gefitinib

Clinical Trials

The first-line efficacy and safety of gefitinib in the treatment of patients with metastatic NSCLC harboring EGFR exon 19 deletions or L858R substitution mutations were demonstrated in a multicenter, single-arm, open-label clinical study (Study 1). A total of 106 treatment-naive patients with metastatic EGFR-mutation-positive NSCLC received gefitinib at a dose of 250 mg once daily until disease progression or unacceptable toxicity occurred. The primary efficacy outcome measure was the objective response rate (ORR) as assessed by blinded independent central review (BICR) and investigators according to RECIST v1.1 criteria. Duration of response (DOR) was an additional outcome measure. Eligible patients were required to have prospectively confirmed the presence of EGFR exon 19 deletions or L858R, L861Q, or G719X substitution mutations, and the absence of T790M or S768I mutations or exon 20 insertions in their tumor specimens via clinical trial testing. Retrospective testing of tumor samples from 87 patients was performed using the Gefitinib® EGFR RGQ PCR Kit.

Study Population Characteristics: The median age was 65 years, with 25% aged 75 years or older and 49% younger than 65 years; 100% were White, 71% were female, 64% were never-smokers, 45% had a WHO performance status (PS) of 0, 48% had a WHO PS of 1, 7% had a WHO PS of 2, and 97% had adenocarcinoma histology. Among the patients, 60 had exon 19 deletions (65%), 29 had L858R substitutions (31%), and two patients each had tumors harboring L861Q or G719X substitution mutations. The median duration of treatment was 8.0 months.

Efficacy Results

Blinded Independent Central Review (BICR) assessment (n=106): The objective response rate (ORR) was 50% (95% CI: 41, 59), with a complete response (CR) rate of 0.9% and a partial response (PR) rate of 49%. The median duration of response (DOR) was 6.0 months (95% CI: 5.6, 11.1).

Investigator assessment (n=106): The ORR was 70% (95% CI: 61, 78), with a CR rate of 1.9% and a PR rate of 68%. The median DOR was 8.3 months (95% CI: 7.6, 11.3).

Footnote: Seventeen patients with no measurable target lesions detected by BICR at baseline were considered non-responders; determined according to RECIST v1.1.

Response rates were similar in patients with tumors harboring EGFR exon 19 deletions and exon 21 L858R substitution mutations. Partial responses were observed in both patients with tumors carrying G719X substitution mutations, with durations of response of at least 2.8 months and 5.6 months, respectively. One of the two patients with tumors harboring L861Q substitution mutations also achieved a partial response, with a duration of response of at least 2.8 months.

FDA，2021.05