IRESSA is a tyrosine kinase inhibitor indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.

EGFR EXON 19 DELETION OR L858R MUTATIONS….Progression on erlotinib (± ramucirumab or bevacizumab), afatinib, gefitinib, or dacomitinib….SUBSEQUENT THERAPY...Continue erlotinib (± ramucirumab or bevacizumab) or afatinib or gefitinib or dacomitinib (if T790M-)

This was an open-label, parallel, phase 3 randomized clinical trial (GAP BRAIN) conducted in 6 centers in China. The main eligibility criteria included histologically or cytologically confirmed NSCLC with EGFR-sensitive mutation (exon 19 deletion or exon 21 L858R mutation)...In this randomized clinical trial, gefitinib plus chemotherapy significantly improved intracranial PFS, PFS, and OS compared with gefitinib alone in patients with untreated EGFR-mutant NSCLC brain metastases...

Pts with newly diagnosed stage III/IV/ recurrent NSCLC harboring an EGFR activating mutations (exon 19 deletion or exon 21 L858R) were randomized...GCP demonstrated significantly better PFS compared to G….Additional OS analysis (G:101 events vs GCP:83 events) revealed that median survival time of GCP was much longer than that of G (52.2 months vs 38.8 months, HR:0.695, p = 0.013).

Pts with newly diagnosed stage III/IV/recurrent NSCLC harboring EGFR activating mutations (exon 19 deletion or exon 21 L858R) were randomized 1:1 to G 250 mg PO QD or GCP (G 250mg PO QD combined with carboplatin AUC 5 + pemetrexed 500mg/m2, every 3 weeks)....Although there was no difference in PFS2 between the arms, additional OS analysis (G 101 events vs GCP 83 events) revealed that median survival time of GCP was much longer than that of G (52.2 months vs 38.8 months, HR: 0.695, p = 0.013)....NEJ009 was the first phase III study which evaluated the efficacy of a combination of EGFR-TKI and platinum doublet chemotherapy in untreated advanced NSCLC pts with EGFR mutations.

First-line gefitinib for patients with advanced non–small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival, with acceptable toxicity, as compared with standard chemotherapy.

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

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

...- History of one to three prior systemic chemotherapy tumors without active EGFR mutations (exon 19 deletion, L858R mutation in exon 21)...

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

...Locally identified EGFR exon 19 deletion or exon 21 p.L858R. ...

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

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

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

...to provide a testable specimen (tissue or cancerous pleural effusion) before the group to carry out genotyping, test results show EGFR-positive exon 19 deletion or exon 21 (L858R) mutation; 4) major organ function within 7 days prior to treatment, meeting the following criteria: (1) blood routine examination criteria (14 days without blood transfusion): hemoglobin (HB) ≥ 90g/L; neutrophil absolute (ANC) ≥ 1.5×10^9/L; platelet (PLT) ≥80×10^9/L; (2) biochemical tests to meet the following criteria: total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase AST ≤ 2.5 ULN, Liver metastases, ALT and AST ≤ 5 ULN; serum creatinine (Cr) ≤ 1.5 ULN or creatinine clearance (CCr) ≥ 60ml / min; (3) Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ normal low (50%). ...

...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. ...

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

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

...- Target population is completely resected pathological stage IIIA-N2 NSCLC with EGFR exon 19 deletions and exon 21 L858R activating mutation....

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

...- EGFR exon 19 deletion or exon 21 L858R....

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

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

...Detection of EGFR-positive exon 19 deletion or exon 21 (L858R) mutation was performed by providing a detectable specimen (tissue or cancerous pleural effusion) prior to enrollment; 5....

...EGFR mutation assessment:...

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

...EGFR exon 19 deletion or exon 21 L858R substitution mutation confirmed; 5....

...Must have discontinued any previous anti-cancer and investigational therapy (excluding EGFR TKI) for at least 28 days or radiotherapy ≥14 days before study treatment administration, and must have recovered to Grade 1 from the adverse effects of such treatment before starting study treatment....

This was an open-label, single arm, multi-center phase II trial that included patients aged 19 or older with sensitizing EGFR mutations and stage III NSCLC who had received platinum-based CCRT. Participants were treated with Gefitinib (250mg daily) up to 12 months....53.5% (8/15) of the patients had L858R point mutation and 40% (6/15) of the patients had 19 deletion….Overall response rate was 66.67% (10/15) and disease control rate was 93.33% (14/15).

In this study, tumor tissues were collected from 101 patients with stage II/III resectable NSCLC with an EGFR mutation (57 patients were treated with gefitinib and 44 were treated with chemotherapy) in the ADJUVANT-CTONG1104 trial…use of Vβ20-1Jβ2-3 specifically for EGFR exon 19 del or Vβ9Jβ2-1 specifically for EGFR exon 21 mutation (L858R), and these were significantly associated with favorable overall survival (OS) for NSCLC patients harboring EGFR exon 19 del or exon 21 L858R, particularly in the adjuvant gefitinib setting...high abundance Vβ20-1Jβ2-3 or Vβ9Jβ2-1 may be an immune biomarker for guiding adjuvant gefitinib decisions for NSCLC patients harboring EGFR exon 19 del or EGFR exon 21 L858R.

All patients were administered a first-generation EGFR-TKI (icotinib 125 mg tid or gefitinib 250 mg qd, orally)....The PFS of subgroups in number of metastases >5 vs. <5 and EGFR mutation L858R vs. 19-del were 11.13 months vs. 16.33 months (HR 0.45, 95% CI (0.23–0.91), p = 0.016) and 13.43 months vs. 26.69 months (HR 0.23, 95% CI (0.12–0.46), p = 0.0017), respectively (Figure 3)....early-phase SBRT for the primary lung tumor combined with EGFR-TKI followed by RT may be an alternative choice for advanced NSCLC harboring the EGFR mutation.

Among the 60 patients, 52 patients (86.7%) had exon 19 deletion or L858R mutation, with 49 patients (81.7%) receiving gefitinib as the first-line EGFR TKI. The median PFS and OS from the initiation of EGFR TKI were 10.4 months (95% confidence interval [CI], 7.4–13.2) and 21.3 months (95% CI, 13.4–28.8), respectively.

413 patients of stage IV EGFR mutant NSCLC were analysed...Median PFS for each drug according to mutation is depicted in Table 1....Del19 and L858R mutations differ with respect to prognosis and therapeutics. In our population, del19 cases were more commonly male, and depicted a better PFS on 1st line TKI when compared to L858R positive cases (commonly female).

...EGFR mutation-positive NSCLC received first-generation (1G, gefitinib or erlotinib) or 2G EGFR-TKI (afatinib) as the first-line (1L) systemic therapy....The objective response rate (ORR) for the 1L EGFR-TKI was 63.3%. The median progression-free survivals (PFSs) were 8.6 months (95% CI: 3.8-13.5), 11.7 months (95% CI: 6.6-16.7), 7.7 months (95% CI: 4.9-17.4), and 5.0 months (95% CI: 3.7-6.1) for major uncommon EGFR mutation (G719X, L861Q), compound mutation with major EGFR mutation (Del 19 or EGFR exon 21 p.L858R), other compound mutation, and other uncommon mutations, respectively.

We analyzed EGFR-mutant advanced NSCLC patients treated with first-line gefitinib, erlotinib or afatinib from Jan 2013 to Dec 2016….Of the 931 patients treated with first-line EGFR-TKI other than osimertinib, 140 (15.0%) patients were LTRs; gefitinib (n=85, 60.7%), erlotinib (n=22, 15.7 %), and afatinib (n=33, 23.6%), respectively...Patients with recurrent disease (OR 0.40, p<0.001), Exon 19 deletion (OR 0.58, p=0.007) and without wet pleura (OR 3.11, p<0.001), bone (OR 1.93, p=0.003), CNS (OR 1.69, p=0.018) or other extrathoracic organ (OR 7.09, p=0.001) metastases were associated with LTRs.

...patients with operable stage II-IIIA NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R mutation were enrolled.... ORR, the primary endpoint, was 54.5% (95% confidence interval [CI], 37.7-70.7), and the rate of MPR was 24.2% (95% CI, 11.9-40.4)....Neoadjuvant therapy with gefitinib in patients with stage II-IIIA NSCLC is safe and may be a viable treatment for patients whose tumors have EGFR mutations.

Predefined subgroup analysis showed that PC-G produced favorable HR (0.20, 95% CI 0.05–0.75; P = 0.017) for patients with EGFR mutations (exons 19/21) compared with PC with regard to PFS...In patients with EGFR mutations (exons 19/21), the ORR was 76.9% for the PC-G arm and 50% for the PC arm (P = 0.13).

Patients with NSCLC and EGFR exon 19 deletions have a longer survival following treatment with gefitinib or erlotinib compared with those with the L858R mutation.

All patients had activating EGFR mutations; 20 (54%) had an exon 19 deletion mutation and 15 (41%) had the exon 21 point mutation L858R. All patients had responded clinically to either gefitinib (n=5) or erlotinib (n= 32).

The patient was diagnosed with stage IV NSCLC (T2aN3M1)...An EGFR deletion was detected in exon 19….The patient was treated with gefitinib (250 mg/d) and traditional herbal medicine, modified Bojungikki-tang (BJIKT)….A partial response was achieved, but after 3 months severe papulopustular skin rashes developed and became aggravated with time. Thus, the gefitinib dose was reduced. However, the PFS has been maintained for approximately 78 months.