Gefitinib Mylan is indicated as monotherapy for the treatment of adult patients with locally advanced or metastatic non‑small cell lung cancer (NSCLC) with activating mutations of EGFR‑TK.

Gefitinib (Iressa ) is accepted for restricted use within NHS Scotland...the treatment of adult patients with locally advanced or metastatic non small cell lung cancer (NSCLC) with activating mutations of epidermal growth factor receptor tyrosine kinase (EGFR-TK).

Erlotinib and gefitinib are category 1 (other recommended) options if an EGFR mutation is discovered before giving first-line systemic therapy (eg, pembrolizumab/chemotherapy), and they are category 2A options if an EGFR mutation is discovered during first-line systemic therapy.

Addition of carboplatin and pemetrexed to gefitinib represents a first-line option in patients with EGFR-mutated tumors

This was a phase III randomized trial in treatment-naive patients with advanced NSCLC with an EGFR-sensitizing mutation...The addition of chemotherapy to Gefitinib improved survival outcomes (PFS an dOS) without a significant adverse impact on quality of life.

In addition, gefitinib plus chemotherapy had better intracranial objective response rate (85.0% versus 63.0%, P = 0.002) and overall objective response rate (80.0% versus 64.2%, P = 0.035) than gefitinib alone….The 3-year OS rate was significantly higher in gefitinib plus chemotherapy group (47.4%, 95% CI 36.3-58.7) than in gefitinib group (24.9%, 95% CI 15.1-34.3, P = 0.003)....Inuntreated EGFR mutated NSCLC patients with brain metastases, gefitinib plus chemotherapy significantly improved intracranial PFS, PFS and a tendency of OS than gefitinib alone, and could be the optional first-line treatment.

...phase III trial compared adjuvant gefitinib versus vinorelbine plus cisplatin in 222 patients with EGFR-mutated, stage II–IIA non–small cell lung cancer (NSCLC) following resection...After a median follow-up of 80 months, median disease-free survival was longer in the gefitinib cohort (30.8 vs 19.8 months)....gefitinib in patients with early-stage EGFR-mutated NSCLC was associated with improved disease-free survival compared with standard chemotherapy.

The use of gefitinib in patients with early-stage EGFR-mutated NSCLC was associated with improved disease-free survival compared with standard chemotherapy...The overall survival with adjuvant gefitinib was longer than in historic cohorts.

From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and EGFR-activating mutation were enrolled, receiving gefitinib...Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively...

Osimertinib showed the most favorable DFS, with significant superiority versus erlotinib (HR 0.4, 95% CI 0.24-0.66), gefitinib (0.42, 0.26-0.67), chemotherapy (0.23, 0.15-0.33) and placebo (0.17, 0.12- 0.24), but with no significant improvement versus CT +TKI (0.86, 0.42-1.74)....EGFR-TKIs monotherapy provided more survival improvement for patients with exon 19 deletion than with L858R mutation (HR, 0.31 [0.13, 0.75] for exon 19 deletion, and 0.48 [0.35, 0.65] for L858R mutation, respectively).

The addition of pemetrexed and carboplatin chemotherapy to gefitinib (Iressa) doubled progression-free survival (PFS) and significantly improved overall survival (OS) in patients with non–small cell lung cancer (NSCLC) harboring an EGFR mutation compared with gefitinib alone, according to results from a randomized phase III clinical trial.

For all biomarker subgroups analyzed, survival was similar for gefitinib and docetaxel... EGFR mutation–positive patients had longer progression-free survival (PFS; hazard ratio [HR], 0.16; 95% CI, 0.05 to 0.49; P = .001) and higher objective response rate (ORR; 42.1% v 21.1%; P = .04)...

This was a phase III randomized trial in patients with advanced NSCLC harboring an EGFR-sensitizing mutation and a performance status of 0 to 2 who were planned to receive first-line palliative therapy….Adding pemetrexed and carboplatin chemotherapy to gefitinib significantly prolonged PFS and OS...

The phase III Iressa Survival Evaluation in Lung Cancer (ISEL) trial compared gefitinib with placebo in 1,692 patients with refractory advanced non-small-cell lung cancer. We analyzed ISEL tumor biopsy samples to examine relationships between biomarkers and clinical outcome after gefitinib treatment in a placebo-controlled setting....Patients with EGFR mutations had higher response rates than patients without EGFR mutations (37.5% v 2.6%);...

...- Available tumor tissue for determination of EGFR mutational status and immunohistochemistry analysis...

...Patients with histologically or cytologically confirmed non-squamous non-small-cell lung cancer (NSCLC) stage II, IIIA and IIIB detected preoperatively by adequate methods and activating EGFR mutation in exons 18-21 and deemed to be able to undergo curative surgery after induction therapy....

...(2) EGFR detection sensitive type (with mutations in exons 18, 19, and 21, and no mutation in exon 20);...

...- Must have activating mutations in the TK region of the epidermal growth factor receptor (EGFR) gene...

...- Patients with tissue for the detection of EGFR mutation...

...- Patient who can provide sample for EGFR mutation test...

...EGFR mutation-positive (EGFR exon-18, exon-19 or exon-21); 5. ...

...Pathologically confirmed non-small cell lung cancer with EGFR exon 19 deletion or exon 21 L858 mutation....

...EGFR mutation positive 4....

...- Documented EGFR mutation...

...- Centrally confirmed EGFR exon 19 deletion (del19) or exon 21 mutation (L858R)...

...- EGFR mutations (deletion of exon 19 and L858R mutation of exon 21) for which the clinical benefits of an EGFR-TKI (gefitinib or erlotinib) are recognized by testing methods that are listed by the national health insurance...

...To evaluate the disease free survival of gefitinib combined with radiotherapy as adjuvant therapy in completely resected patients with Pathological stage IIIA-pN2 NSCLC harbouring sensitive mutations of EGFR.Disease free survival (DFS)- defined as the time from initial medication to the first documented disease progression or death, whichever occurs first.`...

...Harboring activating mutation of EGFR,only including an exon 19 deletion or an exon 21 point mutation....

...- Activating EGFR mutations (G719A/C/S; Exon 19 insertion/deletion; L858R; L861Q)...

...- Bim deletion by realtime PCR, or low abundance for EGFR mutation, for 19Del less than 4.9%, for L858R less than 9.5%....

...EGFR mutation (exon 19 deletion or exon 21 L858R) with Bim deletion or low abundance for EGFR mutation....

...Tumors with common EGFR mutations (19del or L858R) 3....

...- Target population is unresectable stage III (III A-bulky N2, III B) NSCLC with EGFR activating mutation in exon 19 or 21...

...- Histologically confirmed stage IIIB/IV or recurrent NSCLC with activating EGFR mutation in exon 18 through exon 21 except T790M...

...Patients with deletion of exon 19 or mutation of L858R at exon 21 in EGFR gene 4....

...EGFR mutation assessment:...

...- EGFR mutation status unknown....

...Sensitive EGFR mutations (19del, 21L858R); 5....

...- Sequencing EGFR mutation(primary lesion or metastases,exon 19 deletions or exon 21 L858R (EGFR mutation in exon 21, L858R point mutation) mutations;...

...- Activating mutation of EGFR...

...- Locally advanced or metastatic EGFR mutation positive NSCLC...

...The following characteristics of the 'long-term responders' from the EAP; gender, ethnicity, smoking history (pack years), EGFR-TK mutation and histology of NSCLC....

...- Patients with tumor EGFR mutation positive (exon 19 deletion mutation or exon 21 L858R substitution mutation);...

...Time to maximum response`Overall survival`Prevalence of EGFR & KRAS mutation from laboratory result...

...Documented evidence of tumor harboring an activating EGFR mutation (Example 19 del and 21 L858R). ...

...EGFR exon 19 deletion (19del) or exon 21 mutation (L858R) has been confirmed....

...Harbouring activating EGFR mutations (either exon 19 deletion or L858R in exon 21); 4. ...

...1) patient confirmed NSCLS; 2) MRI indicated that the measurable brain metastasis lesion; 3) patient with EGFR mutations; 4) age 18 ~ 75 years old;ECOG PS 0 ~ 2 points;Life expectancy > 3 months; 5) all subjects or their guardians must sign the subject informed consent before entering the test....

...Evidence of activating mutations of EGFR and can be treated with gefitinib; 5. ...

...- Cytological or histological confirmation of NSCLC other than predominantly squamous cell histology with an activating EGFR TK mutation as determined locally...

...The gene detects EGFR mutations is positive; 3....

...- High likelihood of gefitinib sensitivity, as evidenced by one or more of the following: previous complete or partial response to treatment with an epidermal growth factor receptor-tyrosine kinase inhibitor, erlotinib, or gefitinib; known somatic mutation of the EGFR tyrosine kinase...

...whether patient was detected for EGFR gene mutation was...

...- Patients with positive EGFR exon19 or exon21 mutation as confirmed by direct sequencing histologically....

...- Locally advanced or metastatic non-small cell lung cancer (i.e. cancer that has spread from where it started) which is EGFR mutation positive...

...- Patients pathological diagnosed with NSCLC,with EGFR sensitive mutation;...

...- Evidence of activating mutations of EGFR...

...- EGFR mutations (in exon 18, 19, or 21)*...

...EGFR mutation, exon 19 Del or exon 21 L858R, must be confirmed before enrollment. ...

...According to the US Joint Committee on Cancer Staging Standards, it is not suitable for radical treatment; according to the Chinese non-small cell lung expert consensus on detection of epidermal growth factor receptor gene mutation in cancer patients, recommended detection means to confirm EGFR sensitive base positive for mutation. ...

...NSCLC with an activating sensitizing EGFR mutation...

...- EGFR mutation positive Non-Small Cell lung cancer (NSCLC) (regardless of smoking status), or control group may encompass other molecular subtypes of lung cancer e.g....

...Patients with advanced non-small cell lung cancer (NSCLC) confirmed by histopathology or cytology, who can not be operated or have postoperative recurrence and metastasis [2009 IASLC international lung cancer staging (8th Edition) TNM stage III B-IV, see Appendix 2 of the trial protocol], according to the definition of the joint committee on cancer staging standards, they are not suitable for radical treatment; To confirm EGFR 19del or L858R mutation according to the detection method recommended by "expert consensus on detection of epidermal growth factor receptor gene mutation in Chinese patients with non-small cell lung cancer"; [Chinese Journal of Pathology, 2011,40 (10): 700-702] 2. ...

...Histologically or cytologically confirmed NSCLC with an activating sensitising EGFR TK mutation as determined before starting the first EGFR-TKI treatment by using a well-validated and robust methodology 2. ...

This retrospective study included 97 patients with metastatic NSCLC...The patterns of available systemic treatment, the most common first-line chemotherapy regimen in patients with metastatic NSCLC without driver mutation was platinum + taxanes (46%) while the most common first-line targeted therapy in patients with metastatic NSCLC with EGFR mutant was Gefitinib (89%). The median survival of patients in the non-treated group versus treated group was 1 and 12 months (p<0.05) while the median survival of the chemotherapy group versus targeted therapy group was 11 and 16 months (p<0.05)....

A retrospective analysis was performed on 120 NSCLC patients with advanced EGFRm+ ...and they were divided into the control group (CG, received chemotherapy alone) or the observation group (OG, received chemotherapy and gefitinib) according to the treatment methods (Figure 1)....The chemotherapy and gefitinib treatment improved the DCR better than chemotherapy alone, as evidenced by data in Table 3....The chemotherapy and gefitinib treatment greatly improved the medians of PFS and OS than chemotherapy alone (Figures 2, 3 and Table 4).

All 170 patients received EGFR-TKI treatment for metastatic EGFRm NSCLC….Of the 170 patients, 110 (65%) patients received gefitinib, 56 (33%) received erlotinib and 4 (2%) received afatinib (Table 2)….There were 170 patients available for analysis of the best response to treatment. The objective response rate of first-line EGFR-TKI therapy was 74.7%: 83/170 (49%) had CR/PR, 44/170 (26%) had SD....When compared to type of TKI used in the first-line setting, gefitinib provided a significantly higher response rate (55%) and lower progression rate (19.0%) p = 0.005 compared to erlotinib (Table 4).

A total of 44 patients with EGFR variant–positive NSCLC receiving EGFR-TKI therapy were included...25 (66%) presented PFS of more than 12 months (age at treatment start: 74 (9) years; 76% females; 16 on erlotinib, 4 on afatinib, 4 on osimertinib, 1 on gefitinib).

Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy...The 2-year OS rate was 90% (90% confidence interval: 71.4% to 96.8%), indicating that this trial met the primary objective. The overall response rate and 1- and 2-year progression-free survival rates were 85.0%, 58.1%, and 36.9%, respectively.

The PFS rate at 2 years by independent review was 29.6% (one-sided 95% confidence interval [CI]: 17.6%-). The overall response rate was 81.5% (95% CI: 63.3%-91.3%), median PFS was 18.6 months (95% CI: 12.0-24.5 mo), and median overall survival was 61.1 months...This prospective study revealed the tolerability and the possible efficacy of gefitinib plus concurrent thoracic radiotherapy in patients with LA-NSCLC having EGFR mutation.

The median DFS of stage II/III patients in the gefitinib, erlotinib and icotinib group were 36.1 months (95% CI, 23.9–49.4), 42.8 months (95% CI, 29.6–97.8), and 32.5 months (95% CI, 23.9–49.4), respectively...This first and largest real-world study showed that gefitinib, erlotinib, and icotinib demonstrated comparable clinical effectiveness as adjuvant therapy in completely resected patients with EGFR mutated NSCLC.

There were 813 patients enrolled, with 562, 106, and 32 received first-line gefitinib, erlotinib, and osimertinib, respectively, while 113 received second-line osimertinib. At a median follow-up of 18.1 months, the median OS was 45.5 months. 

GOAL was a multicenter, randomized phase IB/II study performed in two countries, Spain and Mexico. Eligible patients were 18 years or older, treatment-naïve, pathologically confirmed stage IV NSCLC, with centrally confirmed EGFR mutations and measurable disease....91 received gefitinib and 91 received gefitinib plus olaparib....The gefitinib plus olaparib combination did not provide significant benefit over gefitinib alone.

CONTRADICTING EVIDENCE: Among unresectable locally-advanced NSCLC patients with EGFR mutation, gefitinib with concurrent thoracic radiotherapy did not improve PFS rate at 2 years.

15 of 17 EGFR-mutant patients received EGFR-TKI therapy with gefitinib (n = 13) or osimertinib (n = 2). The OS tended to be longer in the TKI group than in the CT or BSC group (16.9 months vs. 7.2 months or 9.8 months, p = 0.059). Among the 34 super-elderly NSCLC patients with a PS score of 3-4, 7 with EGFR-mutant received gefitinib therapy and the remaining 27 received BSC alone. The OS tended to be longer in the TKI group than in the BSC group (4.6 months vs. 2.3 months, p = 0.060).

Pemetrexed was not associated with survival benefit than gefitinib therapy among pre-treated NSCLC patients. While, gefitinib showed superior PFS efficacy than pemetrexed for patients with EGFR mutation-type.

Compared with gefitinib alone, gefitinib combined with carboplatin plus pemetrexed improved PFS in patients with untreated advanced NSCLC with EGFR mutations with an acceptable toxicity profile, although its OS benefit requires further validation.

Of the 84 patients harboring a sensitizing EGFR mutation who were treated with either erlotinib or gefitinib, 56 patients (67%) achieved an objective response (1 complete response, 55 partial response). 

Patients with sensitive EGFR mutations received first-line treatment with gefitinib followed by retreatment with gefitinib after disease progression….The median PFS-1 and PFS-2 were 10.0 months and 14.0 months, respectively. The median overall survival (OS) was 36.0 months.

EGFR mutation was assessed from DNA of 63 paraffin-embedded small needle biopsy/aspiration specimens from 62 patients with NSCLC treated with gefitinib….Patients with EGFR mutations had a significantly better response rate compared to that of the nonmutation group (p < 0.001).

First-line therapy with gefitinib administered in a genotype-directed fashion to patients with advanced NSCLC harboring EGFR mutations results in very favorable clinical outcomes with good tolerance.

This was a phase 2, multicenter, randomized study conducted in East Asian patients with advanced nonsquamous NSCLC with EGFR mutations. Patients were randomized (2:1) to receive P+G (500 mg/m2 intravenously 3-weekly + 250 mg/day orally) or gefitinib...Median OS was 43.4 months in P+G versus 36.8 months in gefitinib arm; adjusted HR 0.77 (95% CI, 0.5-1.2); one-sided P=0.105. Median PFS was significantly longer in the P+G (16.2 months) versus gefitinib arm (11.1 months); adjusted HR 0.67 (95% CI, 0.5-0.9); one-sided P=0.009. In the P+G and gefitinib arms, median PFS was 22.6 and 11.0 months, respectively, in patients with low thymidylate synthase (TS) expression, and 12.6 and 9.9 months, respectively, in patients with high TS expression.

... epidermal growth factor receptor (EGFR) kinase domain mutations are a common cause of non-small-cell lung cancer (NSCLC), a major subtype of lung cancers. Patients harboring most of these mutations respond well to the EGFR inhibitors Gefitinib and Erlotinib initially, but soon develop resistance to them due to the emergence of the gatekeeper mutation T790M.