GILOTRIF is a 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.

Non-Small Cell Lung Cancer: EGFR Mutation Positive…(eg, exon 19 deletion or L858R)…Afatinib 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-)

As expected, TTSP/PFS were longer for pts with ECOG PS 0/1 vs 2, and for pts with Del 19 or L858R mutations, vs those with uncommon mutations, which may be due to the high prevalence (44%) of pts with exon 20 insertions included in this study. Considered table data too.

Ten (43%) pts have achieved confirmed OR (complete/partial response: 1 [4%]/9 [39%]) and 10 (43%) pts have had stable disease....afatinib (30 mg/day) demonstrated a predictable safety profile in pts aged ≥70 yrs with Del19/L858R EGFRm+ NSCLC.

Randomisation was stratified by EGFR mutation (Leu858Arg, exon 19 deletions, or other; block size three)....First-line afatinib significantly improves progression-free survival with a tolerable and manageable safety profile in Asian patients with EGFR mutation-positive advanced lung NSCLC.

Median PFS among those with exon 19 deletions and L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months for chemotherapy (HR, 0.47; 95% CI, 0.34 to 0.65; P = .001).

...Evidence of common EGFR mutation (Del 19 and/or L858R)...

...The tumour harbours common EGFR mutations (Del19, L858R) at start of first-line treatment...

The presence of common baseline EGFR mutations (Del19, L858R) was associated with significantly prolonged median OS (49.6 vs. 30.1 months; P=0.017)….Afatinib was effective in Korean patients with EGFR mutation-positive NSCLC with median OS over 4 years.

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).

The median TTF was longer in patients with common EGFR mutation subgroup (Del19 and L858R) versus uncommon mutation subgroup (17.5 vs 13.8 months, p=0.045) and without versus with brain metastases at baseline (17.5 vs 15.1 months, p=0.049)….Afatinib showed promising clinically meaningful effectiveness and was well-tolerated in Vietnamese EGFR-mutant NSCLC patients.

Patients (pts) with EGFRm (Del19 or L858R) after failure of osimertinib treatment were assigned to a regimen of afatinib 20mg daily combined with carboplatin AUC5 mg/ml/min and pemetrexed 500mg/m2 every 3 weeks...By mutation type, ORR were similar for Del19 and L858R (46.7% and 50.0%, respectively)...

In univariate analysis, pts with exon 19 deletion (del) (n = 130) had significantly longer median OS compared to those with other mutations (L858R: 84, others: 23) (30 vs. 22 M, p = 0.047), without difference in PFS (p = 0.138). Pts treated with afatinib (n = 60) showed significant longer median OS compared to those treated with 1st gen TKIs...significantly better PFS (p = 0.042) and trend in OS (p = 0.069) were observed in pts receiving afatinib in other mutations. Exon 19 del was independently associated with favorable OS (p = 0.028), while age > 70 years (p = 0.017)....The EGFR exon 19 del was associated with favorable OS in advanced NSCLC pts receiving first-line EGFR TKIs.

The objective response rate (ORR) was 78.2%, with median progression-free survival (PFS) of 20.5 months (95% CI 12.7, 28.3) and median overall survival (OS) of 37.5 months (95% CI 19.2-55.8). Outcomes by age (<70 vs ≥70 years) were ORR of 82.6% vs 73.9%, median PFS of 20.2 months (95% CI 14.8-25.6) vs 24.1 (9.8-38.3), and median OS of 45.1 months (95% CI, 17.0-73.1) vs 33.9 (28.7-39.1), respectively....PFS in our patients was longer than reported in clinical studies with similar response rates and toxicity, even in older patients, reflecting a good risk-benefit from afatinib in patients with Del19-EGFR NSCLC.

In the 152 patients enrolled in GIDEON (69.7% female, 64.5%/22.4%/13.2% with Del19/L858R/other exon 18-21 mutations...twelve-month PFS rate was 58.9% and 43.9%, median PFS was 17.2 months and 10.6 months, ORR was 72.0% and 76.5%, twelve-month OS rate was 79.1% and 79.2%, 24-month OS rate was 52.0% and 61.7%, and median OS was 30.4 months and 27.4 months, respectively....Patients with EGFRm + NSCLC aged ≥70 years showed clinical benefit from first-line afatinib with no unexpected safety signals, supporting the use of afatinib in this setting.

48 patients with EGFR-positive NSCLC were identified and divided into subgroups by mutation. Progression-free survival (PFS), overall survival (OS) and time to treatment failure (TTF) in those who were treated with Afatinib (Giotrif®) were evaluated….Patients with common mutations, deletion in exon 19 and L85R, had median OS of 31 months (95% CI: 22-51) and 23 months (95% CI: 6-33) and a median PFS of 16 months (95% CI: 9-33) and 10 months (95% CI: 6-22), respectively.

Del-19 mutations were identified in 52 patients and L858R in 67. The starting dose of afatinib was as follows: 20mg/30mg/40mg in 14 (12%)/ 42 (35%)/ 63 (53%), respectively….The ORR in all patients was 67% (95%CI: 57-75%), and disease control rate (DCR) 96% (95%CI: 90-99%). The median PFS (mPFS) was 18.4 (95% CI, 13.2-23.7) months (58 censored cases). ORR/mPFS were 67%/18.4 months in Del-19, and 61%/15.8 months in L858R.

...all patients with metastatic NSCLC harboring common EGFR mutations (exon 19 deletion or exon 21 L858R substitution) fulfilling the above criteria in Queen Mary Hospital in Hong Kong were included….Patients treated with afatinib in the first-line setting had significantly longer OS compared with those on gefitinib or erlotinib with median OS of being 44.6 months for patients on gefitinib and 48.6 months for patients on erlotinib, and 59.2 months for patients on afatinib....The results are in favor of afatinib (Figure 1). With multivariate analysis adjusted for age, gender, smoking status and the initial EGFR mutation, the result was statistically significant with HR of 0.373 (95% CI: 0.152–0.911, p = 0.031) for afatinib over gefitinib.

In this non-interventional, global study (NCT04179890), existing medical/electronic records were identified for consecutive EGFR TKI-naïve patients with EGFR mutation-positive NSCLC (Del19 or L858R) treated with first-line afatinib….Median OS was 36.5 months (95% CI: 32.9–41.8; Fig. 1B, Table 3)....The ORR with afatinib was 73.6% (Table 3); median duration of response (DoR) was 9 months (IQR: 3–17). The disease control rate (DCR) was 100%. Of 178 evaluable patients, 3 (1.7%) had a complete response (CR), 128 (71.9%) had a partial response (PR) and 47 (26.4%) had stable disease (SD). In patient subgroups the ORR ranged between 67.3% (non-Asian patients) and 91.3% (brain metastases present; Table 3).

In this non-interventional, global, multi-center study (NCT04179890), existing medical or electronic health records were identified for consecutive EGFR TKI-naïve patients with EGFRm+ NSCLC (Del19 or L858R) treated in regular clinical practice with first-line afatinib and, following the detection of T790M, second-line osimertinib. ORR with afatinib and osimertinib was 74% and 45%. TTF, OS and ORR were generally consistent across subgroups.

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).

This was a single-arm, open-label, phase II study, performed in multiple centres in Japan. Previously untreated patients, aged ≥75 years, with EGFR mutation-positive (Del19 or L858R) advanced NSCLC were treated with afatinib...ORR was 75.7% (2 complete responses and 26 partial responses). Median progression-free survival was 14.2 months (95% confidence interval [CI], 9.5-19.0). Median overall survival (OS) was 35.2 months (95% CI, 35.2-not reached); the 2-year OS rate was 78.3%.

We included advanced nonsmall cell lung cancer (NSCLC) patients who had EGFR exon 19del mutation and treated with afatinib or first-generation TKIs...After 12.9 months (mo) of follow-up, the median PFS was statistically longer in the afatinib arm than erlotinib/gefitinib arm (19.3 mo vs. 11.9 mo, p: 0.046)...The 24-mo overall survival rate was 76.1% and 49.5% in the afatinib arm and erlotinib/gefitinib arm, respectively.

Patients with treatment-naive stage IV EGFR-mutated (L858R or del19) NSCLC were enrolled. Orally osimertinib 80 mg once a day for 8 weeks, followed by afatinib 20 mg once a day for 8 weeks, which was repeated alternately….The ORR and one-year survival rate were 69.6% (95% CI: 54.2%-82.3%) and 93.48% (95% CI: 81.13%-97.85%), respectively….Although current study didn’t meet the primary endpoint of one-year PFS rate, alteration therapy with osimertinib and afatinib demonstrated promising efficacy...

9 patients (14F/5M), median age 56 (range 34-75) were enrolled. 12 had EGFR del19, 7 L858R...The ORR after neoadjuvant afatinib was 11/19 (58%; 95% CI, 33-80%)….In stage III EGFRm NSCLC, 2 months of neoadjuvant afatinib is associated with an ORR comparable to that seen in advanced disease and does not impair receipt of SOC chemoradiotherapy ± surgery. PFS and OS are favorable in this single-arm study.

Afatinib is effective in pts with NSCLC with major uncommon and compound EGFR mutations, with broad activity against other uncommon EGFR mutations...Uncommon mutations were classed as: de novo T790M; exon 20 insertions (Ins20); major uncommon mutations (G719X/L861Q/S768I)....Includes patients with MU + Del19/L858R compound mutations.

EGFR mutation subtypes included exon 19 deletion (56.6%) and L858R point mutation (43.4%). The median PFS, time to treatment failure and overall survival were 12.6 months (95% CI: 9.7–14.3), 18.6 months (95%CI: 16.0-21.2) and not reached. The PE was met. The objective response and the disease control were 66.6% (95% CI: 51.7-78.5) and 92.5% (95% CI: 81.8-97.9). Low dose afatinib would be considered as one of standard therapy for EGFR mutation-positive NSCLCs because of promising clinical eficacy...

...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.

This study was a multicenter, single-arm, open-label phase II trial. Treatment-naïve patients with advanced NSCLC positive for common EGFR mutations received afatinib in a dose of 20mg/day….EGFR mutation subtypes included exon 19 deletion (56.6%) and L858R point mutation (43.4%)...The objective response and the disease control was 66.6% (95% CI: 51.7-78.5) and 92.5% (95% CI: 81.8-97.9)....Low dose afatinib would be considered as one of standard therapy for EGFR mutation-positive NSCLCs because of promising clinical efficacy and good tolerability.

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.

Median time on treatment with afatinib and osimertinib was 27.7 months (90% CI: 26.7–29.9). Median OS was 37.6 months (90% CI: 35.5–41.3); median OS was 41.6 and 44.8 months in Del19-positive patients and Asian patients, respectively.

In real-world clinical practice, sequential afatinib and osimertinib was associated with encouraging outcomes in patients with EGFR mutation-positive NSCLC, especially in Del19-positive patients and Asian patients.

Previously untreated patients, aged ≥ 75 years, with EGFR mutation-positive (Del19 or L858R) advanced NSCLC were treated with afatinib 40 mg until disease progression or unacceptable toxicity….Median progression-free survival was 14.2 months (95% confidence interval [CI], 9.5–19.0). Median overall survival (OS) was 35.2 months (95% CI, 35.2–not reached); the 2-year OS rate was 78.3%....

This difference in PFS was maintained even when we restricted our analysis to patients who first received afatinib or osimertinib (respectively, 7 vs. 15.5 months; P < .002; HR = 0.81;...Median PFS across EGFR subtypes was as follows: exon 19 del (17 months), L858R (18 months), G719X/L861Q (7 months), and exon 20 insertion (5 months). Median OS across EGFR subtypes was as follows: exon 19 del (63 months), L858R (73 months), G719X/L861Q (30 months), and exon 20 insertion (16 months).

This difference in PFS was maintained even when we restricted our analysis to patients who first received afatinib or osimertinib (respectively, 7 vs. 15.5 months; P < .002; HR ¼ 0.81;...Median PFS across EGFR subtypes was as follows: exon 19 del (17 months), L858R (18 months), G719X/L861Q (7 months), and exon 20 insertion (5 months). Median OS across EGFR subtypes was as follows: exon 19 del (63 months), L858R (73 months), G719X/L861Q (30 months), and exon 20 insertion (16 months).

ORR for the total treated population was 73% with a DCR of 90 %....Afatinib is a standard therapy for patients with activating EGFR mutations in Germany. The first results of this prospective NIS confirm the robust clinical data for Afatinib in the clinical routine setting...

Subgroup analysis showed that the patients with exon 19 deletion had significantly longer overall survival benefit from afatinib therapy than 1G EGFR-TKI. (vs. gefitinib, p = 0.0016; vs. erlotinib, p = 0.0135).

...study used medical records of TKI-naïve pts with EGFRm+ (Del19/L858R) NSCLC treated with first-line afatinib...Median time on treatment and TTP was 18.7 mos and 20.8 mos respectively and was not impacted by reduced starting dose or dose modification (19.4/17.7/19.5 and 25.9/20.0/29.0 mos for pts who started on ≤30 mg/reduced to <40 mg/remained on ≥40 mg)...Time on treatment/TTP were similar regardless of dose adjustment or reduced starting dose, confirming the efficacy of this regimen.

We thus evaluated the efficacy and tolerability of low-dose afatinib maintenance treatment among patients with NSCLC harboring EGFR mutations who had not been previously treated....Among 30 patients, 93% had adenocarcinoma, 53% had exon 19 deletion, 37% had L858R, and 10% had minor mutations. The 1-year PFS rate was 50% (95% confidence interval [CI], 31.3-66.1) and the median PFS was 11.8 months (95% CI, 7.1-21.4).

Twenty‐six (43.3%) patients harbored exon 19 del, 16 (26.7%) patients harbored exon 21 L858R, and 18 (30.0%) patients harbored uncommon sensitive EGFR mutations, among whom five patients had both common and uncommon mutations….The median PFS of patients with common sensitive EGFR mutations (L858R or 19del) was 3.0 months (95% CI 0.4–5.5), while the median PFS of patients with uncommon sensitive mutations was 6.6 months (95% CI 5.0–8.2; P = 0.119) (Fig ​(Fig22b).

Median times on sequential and individual EGFR TKI treatments were numerically longer in patients with Del19 versus L858R mutations (overall 29.9 vs 18.8 months; afatinib 12.2 vs 9.4 months; osimertinib 15.0 vs 9.4 months) and in patients with ECOG PS 0/1 vs ≥ 2 (overall 31.3 vs 20.9 months; afatinib 12.0 vs 10.0 months; osimertinib 15.9 vs 8.4 months).

...we investigated the total TOT along with four treatment options starting from first-line afatinib treatment to various subsequent treatments, including osimertinib and cytotoxic chemotherapy....Regarding the subtype of EGFR mutations, the median total TOTs were 26.40 months (95% CI: 24.08–29.34 months), 20.60 months (95% CI: 19.91–26.45 months), 11.40 months (95% CI: 8.61–16.33 months), and 15.40 months (95% CI: 5.22–18.00 months) for Del19, L858R, uncommon mutations, and compound mutations, respectively (P<0.001).

Sixty-six patients had more than one EGFR mutation, including those coexisting with exon 19 deletion or L858R mutation. In treatment-naïve patients with advanced stages (n = 72), the objective response rate was 35.8% for gefitinib/erlotinib group and 60.6% for afatinib group (p = 0.036)....For patients with NSCLC harbouring non-resistant uncommon EGFR mutations, afatinib use as the first-line therapy may provide a better treatment response but no survival benefit, as compared with gefitinib or erlotinib.

Afatinib was well tolerated with no new safety signals, and efficacy was encouraging in Korean patients with EGFRm+ NSCLC, including those with baseline brain metastases and/or uncommon EGFR mutations....Overall, patients with tumors harboring mutations in exon 20 (alone or as a compound mutation) had a lower ORR [26.7% (1 CR and 3 PRs among 15 patients)] compared with those with tumors harboring mutations in exons 18, 19, and 21 only (Figure 1). Afatinib showed strong activity against compound mutations, including an ORR of 100% in four patients with tumors harboring mutations in both exon 18 and 21 (Figure 1)...patients may appear in >1 category; specific mutations include: G719X (exon 18), Del19 (exon 19), S768I (exon 20), L858R and L861Q (exon 21).

...we report the case of a 51-year-old woman affected by advanced adenocarcinoma harboring an exon 19 deletion in the EGFR gene, who was treated with second-generation EGFR-TKI following a scheduled gradual dose reduction to better manage toxicities. Following prescription labeling, treatment was initiated at a dose of 40 mg daily. After a few months, the dose was reduced to 30 mg daily owing to grade 3 skin toxicity. A metabolic complete tumor response was observed after 1 year of treatment, then therapy was continued at 20 mg daily, enabling disease stabilization. In conclusion, low dose afatinib was effective in an EGFR-mutant non-small cell lung cancer patient who required dose reductions to better manage toxicities.

...we report the case of a 51-year-old woman affected by advanced adenocarcinoma harboring an exon 19 deletion in the EGFR gene, who was treated with second-generation EGFR-TKI….A metabolic complete tumor response was observed after 1 year of treatment, then therapy was continued at 20 mg daily, enabling disease stabilization. In conclusion, low dose afatinib was effective in an EGFR-mutant non-small cell lung cancer patient who required dose reductions to better manage toxicities.