The 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 receiving first-line, maintenance, or second or greater line treatment after progression following at least one prior chemotherapy regimen.

The NCCN NSCLC Panel recommends erlotinib and gefitinib as first-line therapy options in patients with metastatic nonsquamous NSCLC who have known active sensitizing EGFR mutation...The most commonly described mutations in EGFR (exon 19 deletions, p.L858R point mutation in exon 21) are associated with responsiveness to EGFR tyrosine kinase inhibitor (TKI) therapy... 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-).

Eligible participants were adults (>18 years) with NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease (neoadjuvant or adjuvant chemotherapy ending ≥6 months before study entry was allowed)....At data cutoff (Jan 26, 2011), median PFS was 9·7 months (95% CI 8·4-12·3) in the erlotinib group, compared with 5·2 months (4·5–5·8) in the standard chemotherapy group (hazard ratio 0·37, 95% CI 0·25–0·54; p<0·0001).

Exploratory subset analysis of EGFR mutation restricted to Ex19del indicated that, for gefitinib versus erlotinib, the PFS, RR, and DCR were 11.1 and 11.5 months (HR, 1.120; 95% CI, 0.813 to 1.544; P = .487), 65.4% and 65.1% (P = .965), and 83.3% and 91.6% (P = .113), respectively.

...If tumor histology is adenocarcinoma, must have wild-type EGFR genotype as assessed by a validated assay that includes exon 19 deletion and exon 21 (L858R) substitution....

...- Patients must have lung cancer with a documented EGFR activating mutation (exon 19 deletion, L858R, L861Q)...

...EGFR mutation:...

...The tumor harbors an exon 19 deletion or exon 21 L858R mutation in EGFR, confirmed locally....

...- Presence of one of the EGFR activating mutations in the tumor (exon 19 deletion or L858R, G719X or L861Q)...

...- IIIA NSCLC patients according to TMN-staging of Lung Staging Standard version 7 2009, confirmed by histopathology or cytology after radical operation, and having EGFR exon 19 deletion mutation or exon 21 L858R single base substitution;...

...Number of participants with EGFR mutation (L858R/ exon 19 deletion) and who achieved clinical benefit status was reported. ...

...Inclusion Criteria of Target Disease: IIIA NSCLC patients according to TMN-staging of Lung Staging Standard version 7 2009, confirmed by histopathology or cytology after radical operation, and having EGFR exon 19 deletion mutation or exon 21 L858R single base substitution; Accept study adjuvant therapy within 4 weeks post radical operation; ECOP PS 0-1; Life expectancy >=12 weeks. ...

...- Confirmed with Exon 19 deletion or L858R EGFR mutation...

...Histologically or cytologically confirmed surgically unresectable locally advanced or metastatic (stage IIIB/IV) non-squamous NSCLC with wild-type (excluding major activating mutation (exon 19 deletion and/or exon 21 L858R mutation)) EGFR gene status confirmed by a highly sensitive PCR assay 3....

...histologically confirmed EGFR exon 19 deletion or exon 21 mutation in the diagnostic phase of the study...

...- Primary tissue from patient's surgery must be epidermal growth factor receptor (EGFR)-positive by certain tests...

...- Have molecular evidence of an epidermal growth factor receptor mutation (EGFRmt) known to be associated with EGFR tyrosine kinase inhibitor (TKI) drug sensitivity (G719X, exon 19 deletion, L858R, L861Q)...

...- A tumor that harbors an EGFR mutation known to be associated with drug sensitivity (i.e. G719X, exon 19 deletion, L858R, L861Q)...

...- An EGFR exon 19 deletion and/or an exon 21 (L858R) substitution mutation....

...- Metastatic NSCLC with documented EGFR exon 19 deletion or exon 21 (L858R) substitution mutation...

...- Exon 19 deletion or exon 21 activating mutation in EGFR...

...- Sufficient tumor tissue available for EGFR mutation analysis...

...- Presence of mutation(s) in exon 18 through exon 21 of epidermal growth factor receptor (EGFR), (except T790M single mutation only)...

...A patients with EGFR mutation (including exon 19 deletion, L858R) 5....

...Prior sensitivity to erlotinib or gefitinib or other EGFR TKI....

...- Previously registered to A151216, with the result of lung cancer harboring an EGFR exon 19 deletion or L858R mutation; the testing must have been performed by one of the following criteria: 1....

...- Tumor with a sensitizing mutation in epidermal growth factor receptor (EGFR), defined as follows:...

Patients were divided into 2 groups: EGFR-TKI (erlotinib) monotherapy and EGFR-TKI combined with locoregional therapy (γ knife surgery - GKS or whole-brain radiation therapy)....Exon 19 deletion patients in both groups had longer median OS (26 months) than those with L858R exon 21 (15 months) (p = 0.023).

Similarly, in patients with the EGFR Del19 mutation, afatinib and erlotinib resulted in significantly longer PFS than gefitinib (HR: 0.48 with 95% CI: 0.33-0.71 and HR: 0.54 with 95% CI: 0.36-0.80, 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.

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). 

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.

The postoperative pathology showed lung adenocarcinoma (pT2aN1M0, stage IIA)...with EGFR exon 19 deletion….In November 2017, the patients underwent stereotactic body radiation therapy (SBRT) for metastasis of spinal cord and 6 cycles of EP (etoposide, 100 mg/m2 plus cisplatin 75 mg/m2) therapy and sequential 2 cycles of oral etoposide mono-therapy (100 mg/m2, day1–5, 21 days per cycle), in combination with erlotinib (150 mg per day). The clinical outcome is partial response...