Afatinib (Giotrif) is accepted for use within NHS Scotland...as monotherapy, for the treatment of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor-naïve adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutation(s).

Giotrif as monotherapy is indicated for the treatment of...Epidermal Growth Factor Receptor (EGFR) TKI-naïve adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutation(s).

First-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test

sensitizing EGFR mutation positive...First-line therapy...Afatinib

First-line treatment of EGFR-mutated NSCLC: Patients with a tumour with a sensitising EGFR mutation should receive first-line EGFR TKIs including erlotinib, gefitinib or afatinib [I, A], or dacomitinib.

Afatinib as first-line therapy had better survival outcomes for EGFR-mutated advanced lung adenocarcinoma than gefitinib and erlotinib in the Taiwan population.

Median PFS was 13.0 months [95% confidence interval (CI): 12.0-13.8]; median TTSP was 14.8 months (95% CI: 13.9-16.1). Objective response rate (ORR) was 55.0%....Afatinib demonstrated encouraging efficacy in a broad patient population, including those with brain metastases or uncommon EGFR mutations.

Afatinib administration in routine clinical practice was well tolerated with no new safety signals and demonstrated promising efficacy in patients with EGFRm + NSCLC. 

When restricted to pts harboring common EGFR mutations, median PFS and TTSP were 11.7 months (95% CI 10.1–13.8) and 14.4 months (95% CI 12.9–16.4), respectively. ORR was 57% (59% in pts with common EGFR mutations); median duration of response was 11.1 months (95% CI 8.3–12.3).

This interim analysis shows predictable and manageable safety, and encouraging efficacy with afatinib in a broad patient population with EGFRm+ NSCLC. Subgroup analyses showed encouraging PFS and TTSP, particularly for patients with Del19/L858R+ NSCLC regardless of brain metastases at baseline.

...345 pts (stage IIIB/IV, PS 0–1, chemo naive) were randomized 2:1 (A: 230; PC: 115) to daily A 40 mg or iv PC (500 mg/m2 + 75 mg/m2 q21 days up to 6 cycles)….Treatment with A led to a significantly prolonged PFS vs PC (median 11.1 vs 6.9 mos; HR 0.58 [0.43–0.78]; p=0.0004). In 308 pts with common mutations (Del19/L858R), median PFS was 13.6 vs 6.9 mos, respectively (HR=0.47 [0.34–0.65]; p<0.0001). Objective response rate was significantly higher with A (56% vs 23%; p<0.0001)....LUX-Lung 3 is the largest prospective trial in EGFR mutation positive lung cancer and the first study using pemetrexed/cisplatin as a comparator. Treatment with afatinib significantly prolonged PFS compared to PC, with significant improvements in secondary endpoints.  

...Documented Epidermal Growth Factor Receptor (EGFR) T790M mutation 4....

...Presence of activating mutation(s) in exon 18 to exon 21 of the EGFR-receptor confirmed by direct DNA sequencing of NSCLC tumor tissue....

...- Patients with stage IV epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer who were previously responsive to one line of EGFR tyrosine kinase inhibitor and at least one line of systemic chemotherapy...

...- are EGFR mutation-positive or...

...presence of activating mutation(s) in exon 18 to exon 21 of the EGFR or HER2-neu-receptor confirmed by direct DNA sequencing of NSCLC tumor tissue or increased copy number of the EGFR gene as determined by FISH analysis 4....

...- Documentation of a sensitizing EGFR mutation...

...Histological or cytological confirmed diagnosis of EGFR-mutated NSCLC3. ...

...- EGFR mutation or six months or longer benefit from EGFR TKIs...

...- Non-small cell lung cancer with positive mutation of EGFR verified...

...To detect EGFR T790M and activating mutation status`To assess the physical, physiological and social functions. ...

...For this study, predictive efficacy analyses will be performed with such biomarkers as EGFR mutation status. ...

...Progression or recurrence of disease after receiving prior continuous gefitinib, afatinib, or erlotinib; A tumor known to harbor a de novo T790M mutation, which is known to confer EGFR TKI resistance....

...- Have lung cancer harboring an EGFR mutation...

...- Pathologically confirmed diagnosis of non-small cell lung cancer with EGFR mutation...

...- EGFR- tyrosine kinase inhibitor (TKI) naive patients with histologically confirmed locally advanced or metastatic NSCLC with activating EGFR-mutations...

...EGFR(Epidermal Growth Factor Receptor) mutation detected by central laboratory analysis of tumor biopsy material 3....

...Epidermal Growth Factor Receptor mutation positive result per the institution's testing methodology....

...- Patients with Epidermal Growth Factor Receptor (EGFR) mutation-positive inoperable or recurrent non-small cell lung cancer (NSCLC)will be included....

...Types of mutations in signaling kinases associated with therapeutic response`Allelic ratio of wild type to mutant EGFR (roughly corrected for intrinsic differences in tumor cellularity) with duration of response...

...Pathologically confirmed diagnosis of Stage IIIB or Stage IV adenocarcinoma of the lung, with EGFR mutations-positive status, who are...

...- presence of Epidermal Growth Factor Receptor (EGFR) mutations in tumor biopsy...

...Epidermal Growth Factor Receptor (EGFR) mutation-positive results per the institution's testing methodology 3....

...Phase I Step: AUC0-24, AUCtau,ss of BIBW 2992 After Multiple Oral Administration`Phase II Step: Clinical Benefit`Phase II Step: Time to Objective Response`Phase II Step: Duration of Objective Response`Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings`Phase II Step: Duration of Clinical Benefit`Phase II Step: Progression-free Survival (PFS)`Phase II Step: Overall Survival (OS)`Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE`Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline`Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course1 Day 15`Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 1`Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 15`Phase II Step: Summary of EGFR Mutation Findings`Phase I Step: Cmax,Cmax,ss of BIBW 2992 After Multiple Oral Administration...

...- Epidermal Growth Factor Receptor (EGFR) mutation-positive result per the institution's testing methodology....

...- Patients who are diagnosed with locally advanced or metastatic NSCLC with EGFR sensitive mutation positive...

...Patients with histologically or cytologically confirmed IIIA or stage IIIB N2 requiring neoadjuvant treatment for pN2 IIIa NSCLCEpidermal Growth Factor Receptor (EGFR) mutation-positive result per the institution’s testing methodology. ...

...- Patients must have tumours harbouring a sensitising EGFR mutation or HER2 mutation in at least one biopsy at recurrence, or region of the primary sample....

...- Patients with Epidermal Growth Factor Receptor (EGFR) mutation-positive advanced Non-Small Cell Lung Cancer (NSCLC)...

...- Histologically or cytologically confirmed locally advanced or metastatic (IIIB/IV) NSCLC of any histological type with activating EGFR mutation(s) according to local laboratory EGFR testing;...

...Time on Treatment With Afatinib During Second Line (2L) Treatment Defined by Histology Status`Time on Treatment With Afatinib During Second Line (2L) Treatment Defined by Epidermal Growth Factor Receptor (EGFR) Mutation Status`Chart abstractors (i.e. the patients treating physician) were asked to abstract information regarding severe (grade 3 or higher) irAEs of specific interest (including pneumonitis, colitis, hepatitis, interstitial lung disease, higher indeterminate pulmonary events, death, or discontinuation of therapy due to toxicity) during first line (1L) treatment and second line (2L) for both patients treated with afatinib in 2L and those treated with chemotherapy in 2L. ...

...1) A tumor which harbors an Epidermal Growth Factor Receptor (EGFR) -mutation known to be associated with drug sensitivity (i.e., G719X, exon 19 deletion, L858R, L861Q) from previous tumor biopsy or surgery....

...Patients with tumors harboring EGFR mutation (del 19 or L858R mutation) 6....

...Documented activating EGFR mutation (Del 19 and/or L858R) determined in tumour tissues ? ...

...Documented EGFR mutation(s)-positive NSCLC (common mutations: Del19 and L858R) from tumour biopsy material....

...Diagnosed with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFRTKI) naive advanced EGFR mutated non-small cell lung cancer (NSCLC), 3....

...- Lung adenocarcinoma patient with EGFR sensitive mutation as confirmed by needle biopsy;...

...- Patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC)...

...- EGFR mutated...

...Documented activating epidermal growth factor receptor mutation (Del19 and/or L858R) with tumour tissues....

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

...Confirmed activating EGFR mutation (exons 18-21; e.g....

...Documented EGFR mutation (L858R and/or Deletion 19) with...

...- Epidermal Growth Factor Receptor mutation detected by central laboratory analysis of tumour biopsy material....

...- A somatic mutation in epidermal growth factor receptor (EGFR) must be present as documented by a CLIA-certified laboratory...

...Evaluation of the HER-2 gene copy number and amplification`DNA Extraction and Mutational Analysis of EGFR and HER-2`Toxicity evaluation`Determination of plasma HGF pre and post-treatment concentration...

...Documented somatic EGFR mutation as determined by medically accepted assay technology 3....

...- Evidence of common EGFR activating mutations (Del 19 and/or L858R)...

...Epidermal Growth Factor Receptor (EGFR) mutation-positive result per the institution's testing methodology....

...7) Gene test from tumor tissues confirmed EGFR sensitive mutation positive (including classical mutation and non-classical mutation :19del, L858R, L861Q, G719X, S768I); 8) No brain metastasis, or accompanied by asymptomatic brain metastasis, or symptomatic brain metastasis after treatment which change to stable; 9) Adequate hematological function: neutrophil absolute count >=1.5x10^9/L, platelet count >= 100x10^9/L exclusion, hemoglobin >= 90 g/L; 10) Adequate liver function: all patients whose total bilirubin level is the normal upper limit; 11) Adequate renal function: creatinine clearance rate >= 50ml/min (Cockcroft-Gault formula); 12) Adequate coagulation function: international standardized ratio (INR) or prothrombin time (PT) ...

...* Documented EGFR mutation and any line of therapy (including first-line), or...

...1.Non-squamous NSCLC patients confirmed by imaging and histopathology as III B to IV stage; 2.Positive EGFR gene mutation (including 19DEL, 21L858R, G719A, G719C, G719S, L861Q, V689M, N700D, E709K/Q, S720P, L858R, N826S, A839T, K846R, G863D, G719X, S768I complex mutation, G719X complex mutation, etc.); 3.Has not received any previous systemic anti-tumor therapy; 4.No brain metastases, or asymptomatic brain metastases, or symptomatic brain metastases are treated and stable....

In elderly patients, afatinib showed significantly better efficacy, with a median progression-free survival (PFS) of 14.7 months and overall survival (OS) of 22.2 months, than gefitinib (9.9 months and 17.7 months, respectively) and erlotinib (10.8 months and 18.5 months, respectively; PFS: p=0.003; OS: p=0.026)...For elderly patients with EGFR-mutated advanced NSCLC, afatinib was associated with better efficacy than gefitinib or erlotinib in elderly patients with EGFR-mutated advanced NSCLC as a first-line treatment with acceptable AEs.

EGFR mutants treated with afatinib have improved outcomes compared to gefitinib…

The NMA included observational real-world evidence studies on adult patients with EGFR-mutated advanced NSCLC who received first (gefitinib and erlotinib), second (afatinib), or third (osimertinib) generation EGFR-TKIs as frontline therapy....This real-world evidence shows that afatinib confers better survival than other first-line EGFR-TKIs in East Asian patients with advanced NSCLC.

First-line afatinib demonstrated encouraging efficacy on BMs in NSCLC patients harboring either common or major uncommon EGFR mutations, with manageable toxicities.

Among 79 patients with measurable lesions, ORR and DCR in overall were 60% and 100%, respectively….1-year and 2-year OS were 87% and 72%, respectively….This real-world experience suggested that first-line afatinib is efficacious in Vietnamese patients with EGFR-mutated NSCLC, demonstrating an encouraging survival outcome, high response rate, low incidence of intracranial progression, and manageable tolerability profile.

Forty-seven patients received neoadjuvant Afatinib treatment (40 mg daily)….The ORR was 70.2% (95% CI: 56.5% to 84.0%), meeting the pre-specified endpoint. The major pathological response (MPR), pCR, pathological downstaging, and R0 rates were 9.1%, 3.0%, 57.6%, and 87.9%, respectively....Neoadjuvant Afatinib is feasible for stage III NSCLC+ patients and leads to dynamic changes in the tumor microenvironment.

Afatinib demonstrated better survival outcomes than gefitinib/erlotinib for NSCLC patients harboring major EGFR uncommon mutations and compound mutations.

In the single center study, afatinib demonstrated an encouraging clinical activity in the first-line settings of advanced NSCLC harboring EGFR mutation...

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.

We conducted a study on the effect on brain metastasis in EGFR M(+) patients who received afatinib as the 1st line from the KATRD EGFR cohort data.…The OS of the cohort was promising, especially in patients without brain metastasis.

Mutations were categorized according to their incidence: 1) major uncommon mutations (G719X and L861Q), 2) compound mutations, and 3) minor uncommon mutations (exon 20 insertion, S768I, and de novo T790M)....Afatinib demonstrated activity against tumors harboring major uncommon mutations [median time of treatment (TOT): 20.3 months, 95% confidence interval (CI)=15.1-25.5; overall survival (OS): 30.6 months, 95% CI=26.3-34.8] and compound mutations (median TOT: 12.3 months, 95% CI=7.7-17.0; OS: 29.1 months, 95% CI=20.4-37.7)....Afatinib is effective in patients with NSCLC harboring major uncommon and compound EGFR mutations.

In total, 64 patients from one Chinese site with locally advanced/metastatic EGFRm+ non-small-cell lung cancer, who received afatinib 40 mg once daily, were included….Afatinib provided clinical benefit for patients with EGFRm+ non-small-cell lung cancer across all subgroups.

The median age of the patients was 79 years. The ORR was 80.0% and the disease control rate was 91.4%. The median PFS and OS were 15.6 and 29.5 months, respectivelyAn afatinib starting dose of 30 mg/day could be an effective and safe treatment option for elderly patients.

The EPICAL was a single arm, phase 1b study to evaluate safety, tolerability and anti-tumor activity of first line afatinib combined with anti-EGF vaccination in advanced EGFR-mut patients….Objective response and disease control rates were 78.3% (95%CI = 53.6-92.5) and 95.7% (95%CI = 78.1-99.9), respectively. After a median follow-up of 24.2 months, median progression-free survival (PFS) was 14.8 months (95% CI = 9.5-20.1) and median overall survival (OS) 26.9 months (95% CI = 23.0-30.8).

The summarized disease control rate (DCR) was 87.6% (81.5%, 92.7%), and the overall response rate (ORR) was 58.9% (48.8%, 68.7%). The pooled median progression-free survival (PFS) was 12.4 (10.3, 14.5) months, mean time to failure (TTF) was 15.4 (13.6, 17.2) months, and median overall survival (OS) was 31.6 (26.7, 36.5) months....The efficacy and safety of afatinib has been confirmed by real-world evidence in advanced NSCLC with EGFR mutation, consistent with randomized controlled trial results.

We conducted a prospective multicentre, single-arm, and open-label phase II trial for low-dose afatinib (30 mg/day) use in elderly patients with NSCLC with EGFR mutation...The ORR was 80.0% and the disease control rate was 91.4%. The median PFS and OS were 15.6 and 29.5 months, respectively.

The PFS and OS were 17.1 and 26.7 months respectively in patients with good PS and 12.7 and 18.2 months in those with poor PS (both p < 0.001). In the multivariate analysis, good PS, < 3 metastatic sites, and first-line treatment with afatinib compared with erlotinib and gefitinib were associated with longer PFS....In older patients with EGFR-mutated NSCLC and receive EGFR-TKI treatment, a good PS and < 3 metastatic sites at diagnosis were associated with a longer PFS and OS. In addition, afatinib as first-line treatment was associated with a longer PFS whereas a relatively younger age and no brain metastasis at diagnosis were associated with better OS.

We enrolled patients 65 years or older with EGFR-mutated Stage IIIB-IV NSCLC and evaluated the efficacy and prognosis of first-line EGFR-TKI treatment…. In the multivariate analysis, good PS, <3 metastatic sites, and first-line treatment with afatinib compared with erlotinib and gefitinib were associated with longer PFS. A relatively younger age, good PS, < 3 metastatic sites, and no brain metastasis at diagnosis were associated with better OS.

A total of 59 patients were treated with afatinib for their EGFR mutation-positive advanced NSCLC...At a median follow-up of 41.8 months (95% CI 35.9– 51.4), the median PFS was 14.3 months (95% CI 12.2– 16.4), and the median OS was 29 months (95% CI 25.6– 33.4).

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).

In this non-interventional, global, multicenter, retrospective study (NCT04179890), existing medical or electronic health records were searched for consecutive patients with uncommon EGFR mutations (T790M, ex20ins, major uncommon [G719X, L861Q or S768I], ‘other’, or compound mutations) who were EGFR TKI-naïve at diagnosis, treated with erlotinib, gefitinib, afatinib, osimertinib, or other systemic therapy....Patients treated with afatinib had longer median TTF and DoR, vs those treated with first-generation EGFR TKIs.

This study aimed to retrospectively review the clinical outcomes and safety of afatinib treatment in EGFR-mutation-positive (EGFRm+) NSCLC patients with PS ≥ 2….the objective response rate, disease control rate, median progression-free survival (PFS), and overall survival (OS) were 58.1% (36/62), 69.4% (43/62), 8.8 months, and 12.9 months, respectively....Afatinib demonstrated acceptable efficacy and safety in the current cohort.

Eighty-eight patients received afatinib, including 27 (31%) with brain metastases and 16 (18%) with uncommon EGFR mutations. Median PFS was 17.0 months (95% confidence interval [CI] 12.9–23.3 months)....Afatinib showed encouraging efficacy in a broad patient population including those with brain metastases or tumors harboring uncommon EGFR mutations.

This cohort study analyzed the overall survival (OS) and progression-free survival (PFS) of afatinib compared with erlotinib and gefitinib first-line. EGFRm+, advanced NSCLC patients treated with either afatinib, erlotinib or gefitinib were retrospectively analyzed....Median OS were 19.1, 22.9, and 35.6 months for gefitinib, erlotinib, and afatinib groups, respectively, with statistical significance between the gefitinib and afatinib groups (p = 0.009). Patients on afatinib also had longer median OS than erlotinib and gefitinib pooled together (35.5 versus 21.4 months; hazard ratio = 0.54, p = 0.016), despite similar median PFS.

The efficacy of DCR and ORR were 87.6 % (81.5, 92.7) and 58.9 % (48.8, 68.7)....The efficacy of afatinib in first-line only group was superior than those in second-line....Afatinib was a safe and effective TKI for real-world EGFR-mutated NSCLC patients, which was consistent with the results of RCT.

In NCT02047903, a prospective non-interventional study in Germany, patients with EGFRm+ NSCLC received first-line afatinib until disease progression or intolerable adverse events….Overall, the 12-month PFS rate was 50.2% while the median PFS was 12.2 months. The ORR was 74.6% and the median OS was 30.4 months.

First-line afatinib is beneficial for Vietnamese patients with advanced EGFR-mutant NSCLC with a good response rate and prolonged TTF with manageable adverse event profile. 

Patients had progressed after initial benefit with erlotinib or gefitinib, and/or had an EGFR or HER2 mutation, had no other treatment options, and were ineligible for afatinib trials. The recommended starting dose of afatinib was 50 mg/day….Objective response rate (ORR) was 24% overall (n = 431 with data available), 27% for patients with common EGFR mutations (n = 230) and 28% for those with uncommon mutations (n = 32); median time to treatment failure (TTF) in these groups was 7.6 months (n = 1550), 6.4 months (n = 692) and 8.4 months (n = 83), respectively.

Afatinib is effective for patients with NSCLC harboring common EGFR mutations irrespective of their clinicopathological backgrounds unlike gefitinib and erlotinib.

Those given afatinib had better OS (39.3 vs. 26.0 months; HR 0.65, P = 0.033) and PFS (14.1 vs.11.2 months; HR 0.58, P < 0.001)….The results indicated that afatnib resulted in significantly better OS and PFS than gefitnib and erlotinib for EGFR mutation-positive advanced NSCLC patients without brain metastases.

To assess time-to-treatment failure (TTF) in US patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC)...In 129 patients at US centers, median TTF was 28.4 months (90% CI: 27.0-34.1). Median overall survival was 47.6 months (90% CI: 35.5-51.5)...Sequential afatinib-osimertinib in this US-treated population was associated with long median TTF and represents an effective, evidence-based treatment option for US patients with EGFR mutation-positive NSCLC not presenting with active brain metastases or de novo T790M.

Afatinib is a standard therapy for patients with activating EGFR mut…Among pat. with uncommon EGFR-mut., the 12-months PFS rate was 40.2% with a mPFS of 10.7 months. ORR and DCR were 83.3% and 91.7%...

The ORR was 75.7% (95% confidence interval: CI 61.9-89.5) and DCR was 89.2%. The median PFS was 14.3 months (95% CI 9.9-not reached)....first-line afatinib at a start dose of 40mg/day was found to be well-tolerated by dose adjustment and effective in elderly patients with advanced non-squamous NSCLC harboring EGFR mutations.

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...

Patients who received afatinib for advanced EGFR-mutant NSCLC in 5 institutions in Aomori, Japan from October 2014 to January 2017 were included into the analyses….The median progression-free survival (PFS) was 17.8 months (95% CI: 13.7- 21.5 months). The overall survival (OS) was 39.5 months (95% CI: 34.4- not reached)....In the real practice in Japan, afatinib in first-line and re-challenge settings showed comparable or better efficacy compared with previous clinical trials.

A total of 620 treatment-naive EGFR mutated patients with stage III/IV NSCLC were analysed with follow-up time of 24.5 months. A significantly longer median PFS (p=0.005) and higher 1-year OS rate (p=0.004) for afatinib (16.4 months and 78.2%) vs gefitinib (10.3 months and 69.1%) and erlotinib (12.1 months and 71.6%) were observed.

Afatinib led to longer PFS for patients with common EGFR mutations but not for those with rare mutations.

This was a multicenter, single-arm, open-label, phase II trial involving treatment-naïve patients with advanced EGFR mutation-positive NSCLC….Patients initially received afatinib 20 mg/day orally. For patients in whom the tumor progressed within stable disease, the investigators were able to increase the afatinib dose (10 mg increments)....The median PFS, and overall survival were 12.6 months (90% confidence interval [CI]: 9.7-14.3 months), and not reached, respectively. The primary endpoint was met. The objective response rate and disease control rate were 66.0% (95% CI: 51.7-78.5) and 92.5% (95% CI: 81.8-97.9), respectively.

Targetable EGFR mutations in tumor specimens were detected in 5 patients with predicted non-small-cell lung cancer (5.2%), 4 of whom were treated with afatinib; 2 of these patients achieved a durable PFS of longer than 6 months.

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).

Clinical activity (Asian/non-Asian) was observed against major uncommon mutations (ORR: 66/59%; median DoR: 14.7/15.9 mos; G719X: 62/65%; L861Q: 60/50%; S768I: 80/25%), compound mutations (ORR: 81/100%; median DoR: 11.5/18.6 mos) and other uncommon mutations (ORR: 79/60%; median DoR: 9.0/10.7 mos). Some pts with Ins20 responded (21/23%)…Afatinib is effective in pts with NSCLC with major uncommon and compound EGFR mutations, with broad activity against other uncommon EGFR mutations and some Ins20 mutations, unaffected by ethnicity.

... we found that afatinib and dacomitinib exhibit a monomer preference: cells expressing dimerization-impaired EGFR mutants exhibited increased sensitivity to afatinib and dacomitinib relative to those with dimerization-competent EGFR mutants...These findings provide novel insights into treatment strategies for EGFR-TKI-refractory non-small cell lung cancer.