Real-world evidence

Real-world evidence: a major area of untapped potential?

What is meant by real-world evidence, and why does it matter for physicians? Watch the clip below for some thoughts on this topic.

Rate this

Dr Claas Frohn considers what is meant by real-world evidence, and the role it can play in clinical research and clinical practice. Filmed in November 2018.

The value of real-world evidence to clinical practice

Real-world evidence may complement clinical trials by providing information on the effectiveness and side-effect profile of therapies in patients treated in routine clinical practice.

Rate this

Physicians consider the value of real-world evidence to clinical practice. Filmed in October 2018 at the European Society for Medical Oncology Congress.

RealGiDo: a real-world study of afatinib dose adjustment

Rate this

Watch this animated overview of the RealGiDo study.

RealGiDo was a global, non-interventional study of afatinib* dose adjustment in real-world clinical practice in patients with advanced epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC).1 Over a median time on treatment of 18.7 months (95% confidence interval [CI]: 15.1–21.5), using tolerability to guide afatinib dose adjustments reduced the frequency and intensity of adverse drug reactions (ADRs), without affecting clinical effectiveness.1 As reported in the LUX-Lung trials,2,3 the effectiveness of afatinib was consistent regardless of whether patients had a dose reduction or a modified starting dose.1

The results show that treatment with afatinib can be optimised by tailoring the dose according to individual patient characteristics and ADRs. For more information on the RealGiDo study, view the study page here, a summary of the study here and the online publication here.

Rate this

Professor Angela Märten discusses the RealGiDo study of afatinib dose adjustment in a real-world setting. Filmed in October 2018.

GioTag: a study of sequential therapy with afatinib followed by osimertinib in clinical practice

GioTag was a global, observational study of sequential therapy with afatinib followed by osimertinib in routine clinical practice.4,5 Eligible patients (N=204) had EGFR mutation-positive NSCLC and were treated with first-line afatinib followed by second-line osimertinib on development of the T790M mutation.5 The study reflected the situation in clinical practice more closely than traditional randomised controlled trials as it included patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (15% of patients) and those with and those with central nervous system metastases at baseline (10% of patients).5

At the time of the final analysis (December 2019), median follow-up was 33.9 months.5 Median overall survival (OS) was 37.6 months (90% CI: 35.5–41.3) in the overall patient population, 44.8 months (90% CI: 37.0‒57.8) in Asian patients (n=50), and 41.6 months (90% CI: 36.9‒45.0) in patients with the Del19 EGFR mutation (n=149) (73% of patients had a Del19 mutation; 26% had the L858R mutation).5 The 2-year OS rate from the start of afatinib treatment was 80% in the overall patient population, 90% in Asian patients, and 84% in patients with Del19-positive tumors.5

These findings suggest that sequential afatinib followed by osimertinib can be a feasible and effective therapeutic strategy in real-world patients with EGFR mutation-positive NSCLC who develop T790M, particularly in Asian patients and patients with Del19-positive tumors.5

The main limitations of the GioTag study were its retrospective nature, the lack of a comparator arm, and the potential for selection bias by excluding patients who died after first-line afatinib treatment or under-representing patients who derived long-term benefit from first-line afatinib treatment.5

For more information on the GioTag study, view the study page here, a summary of the study here and the publication here.


Real-world study of afatinib in EGFR-mutation positive NSCLC

A Phase IIIb exploratory trial investigated the safety and efficacy of afatinib in 479 patients with EGFR tyrosine kinase (TKI) inhibitor-naïve, EGFR mutation-positive NSCLC in a real-world setting.6 The patient population included patients with uncommon EGFR mutations (18% of patients had any uncommon mutation; 8% had exon 20 insertions), older patients (aged ≥65 years) and those with comorbidities, poor performance status and brain metastases

In an interim analysis of this study, the objective response rate (ORR) was 46% and median duration of response was 14.1 months (95% CI: 12.2–16.4).6 Median time to symptomatic progression was 14.9 months (95 % CI: 13.8–17.6) and median progression-free survival (PFS) was 13.4 months (95 % CI: 11.8–14.5).6 Most patients (478/479) experienced an adverse event (AE), and Grade ≥3 AEs were reported in 315 (66%) patients.6 The most common any grade treatment-related AEs were diarrhea (87%), rash (51%) and paronychia (30%).6

Overall, afatinib administration in routine clinical practice was well tolerated with no new safety signals, and the safety and efficacy results support previous findings from the LUX-Lung 3, 6 and 7 trials and other real-world studies.6


Safety and effectiveness of afatinib in routine clinical practice

There is an increasing body of real-world evidence on the first-line use of afatinib in routine clinical practice. The combined literature supporting the safety and effectiveness of first-line afatinib in diverse patient populations treated in routine care are discussed in a recent systematic review by Professor Park and colleagues.7

  • Clinical measures of activity in real-world studies, which included patients with brain metastases and uncommon EGFR mutations, are similar to those reported in clinical trials7
  • Available data suggests that the efficacy of afatinib may be favorable in comparison with first-generation EGFR TKIs in patients with common and uncommon EGFR mutations7
  • The tolerability profile of afatinib in real-world studies is similar to that reported in clinical trials7
  • Available data indicates that AEs can be managed with supportive care and/or tolerability-guided dose reduction to minimize the rate of treatment discontinuation7


Summary of comparative real-world studies of afatinib in EGFR mutation-positive NSCLC7

Summary of real-world studies of afatinib

Table adapted from Park et al. (2019).7

*Unadjusted p value.

**Patients with EGFR exon 20 insertions were excluded.

NR, not reached; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; TTF, time to treatment failure.

Afatinib in patients with advanced NSCLC who progressed following prior therapies: results of a global compassionate use program

This afatinib compassionate use program included 5,622 patients with advanced/metastatic NSCLC from 49 countries.17 Data from 3,966 patients in 41 countries were analyzed. All patients had progressed after clinical benefit on erlotinib or gefitinib and/or had a mutation in EGFR or HER2 and had exhausted all other treatment options. Median time to treatment failure with afatinib was 4.4 months in 2,862 patients for which data were available.17 Of these, response assessments were available in 1,141 patients; ORR was 23.4% (267/1,141).17 In patients with an EGFR mutation, the ORR was 25.0% (181/723); ORR was 19.0% (11/58) in T790M mutation-positive patients and 35.0% (7/20) in patients with insertions in exon 20.17 The safety profile of afatinib was as expected in this patient population. Overall, these data suggest that afatinib can provide clinical benefit in heavily pretreated patients with NSCLC, including those with uncommon EGFR mutations. For more information, view the published article here.

Afatinib in advanced NSCLC following progression on prior therapies: subanalysis in Asian centers

A subanalysis was performed in patients who had participated in the afatinib compassionate use program in Asian countries (N=2,242) and received a median of three lines of prior therapy.18 Response data were available from 431 patients; ORR was 24.4% in the overall population, 27.4% in patients with common EGFR mutations (n=230) and 28.1% in patients with uncommon EGFR mutations (n=32).18 Median TTF with afatinib was 7.6 months in 1,550 patients for whom data were available, 6.4 months in patients with common EGFR mutations (n=692), 8.4 months in patients with uncommon EGFR mutations (n=83) and 12.2 months in patients with HER2 mutations.18 The safety profile of afatinib in Asian patients was consistent with that in non-Asian patients.

Did you find this information useful?



Halmos B, et al. Lung Cancer 2019;127:103–11.


Sequist LV, et al. J Clin Oncol 2013;31(27):3327–34.


Hirsch V, et al. Poster presented at ASCO 2016 (Poster 369).


Hochmair MJ, et al. Future Oncol 2018;14(27):2861–7.


Hochmair MJ, et al. Future Oncol 2020;16(34):2799–808.


de Marinis F, et al. Lung Cancer 2021;152:127–34.


Park K, et al. Ther Adv Med Oncol 2019;11:1–17.


 Tu C-Y, et al. Oncotarget 2018;9(36):24237–47.


Kuan FC, et al. Oncotarget 2017;8(1):1343–53.


Lin YT, et al. Int J Cancer 2018;144(11):2887–96.


Ito K, et al. Ann Oncol 2018;29(Suppl. 8): Abstract 1455P.


Kim Y, et al. Cancer Res Treat 2019;51(2):502–9.


Kim Y, et al. J Thorac Oncol 2017;12(Suppl. 2): Abstract P3.01–023.


Shen YC, et al. Lung Cancer 2017;110:56–62.


Skřičková J, et al. J Thorac Oncol 2017;12(Suppl. 2): Abstract P2.03–023.


Fujiwara A, et al. Oncol Res 2018;26:1031–36.


Cappuzzo F, et al. Future Oncol 2018;14(15):1477–86.


Chang G-C, et al. Poster presented at WCLC 2018 (Poster P1.01-11).

*Afatinib is approved in more than 80 markets, including the EU, Japan, Taiwan and Canada under the brand name GIOTRIF®, in the US under the brand name GILOTRIF® and in India under the brand name Xovoltib®; for the full list, please click here. Registration conditions differ internationally; please refer to locally approved prescribing information.


© 2021 Boehringer Ingelheim International GmbH. All rights reserved.


Page last updated: January 2021