Clin Drug Investig
DOI 10.1007/s40261-017-0515-2
CASE REPORT
Complete Tumor Response with Afatinib 20 mg Daily in EGFR-
Mutated Non-small Cell Lung Cancer: A Case Report
Raffaele Giusti1 • Marco Mazzotta1 • Daniela Iacono1 • Salvatore Lauro1
Paolo Marchetti1
Ó Springer International Publishing Switzerland 2017
Abstract Afatinib, a second-generation epidermal growth
factor receptor (EGFR) tyrosine kinase inhibitor, is effi-
cacious as first-line treatment in patients with EGFR-mu-
tated non-small cell lung cancer (NSCLC). Dosage
reduction is recommended in patients with intolerable
adverse events; however, data regarding the efficacy of
low-dose afatinib are limited. We report the case of a
71-year-old female patient who was diagnosed with
advanced EGFR-mutated NSCLC and started treatment
with oral afatinib 40 mg daily. The patient achieved partial
tumor response on computed tomography imaging, but
developed unacceptable skin-related toxicities requiring
dosage reduction to 20 mg daily. The patient subsequently
achieved complete tumor response and showed improve-
ments in performance status. These observations suggest
that low-dose afatinib is effective in patients with EGFR-
mutated NSCLC who require dosage reduction for intol-
erable adverse events.
& Raffaele Giusti
raffaelegiusti@yahoo.it; rgiusti@ospedalesantandrea.it
1 approved for the first-line treatment of advanced EGFR-
Medical Oncology Unit, Sant’Andrea Hospital of Rome, Via
di Grottarossa 1035-39, 00189 Rome, Italy
•
Key Points
The second-generation tyrosine kinase inhibitor
afatinib, at 40 mg daily, effectively prolongs
progression-free survival when used as first-line
therapy in patients with epidermal growth factor
(EGFR)-mutated non-small cell lung cancer
(NSCLC).
Afatinib is often associated with adverse events,
including skin rash, diarrhea, and stomatitis, that
may require dosage reduction.
Although randomized clinical studies with afatinib
have permitted dosage reductions for adverse events
to 20 mg daily, clinical data regarding the efficacy of
afatinib 20 mg daily in NSCLC are limited.
In this case report, low-dose afatinib (20 mg daily)
provided complete tumor response in a patient with
advanced EGFR-mutated NSCLC who experienced
intolerable skin-related toxicities while receiving
higher afatinib dosages.
Low-dose afatinib may be an effective option for
patients with advanced EGFR-mutated NSCLC who
develop intolerable adverse events at higher dosages.
1 Introduction
Afatinib is a second-generation, irreversible inhibitor of
epidermal growth factor receptor (EGFR) [1], and is
mutated non-small cell lung cancer (NSCLC) [2–4]. As

with other EGFR tyrosine kinase inhibitors (TKIs), the
most common adverse events with afatinib are diarrhea,
skin rash, paronychia, and stomatitis. The grade and the
severity of drug toxicity can lead to dosage reduction or
permanent treatment discontinuation. According to label-
ing recommendations, the starting dosage of afatinib
should be 40 mg daily, although dosage reduction to 30 or
20 mg daily is possible if treatment is not tolerated [2–4].
In the first-line treatment of EGFR-mutated NSCLC,
randomized clinical studies have demonstrated the superior
efficacy of afatinib 40 mg daily in prolonging progression-
free survival (PFS) compared with the first-generation
EGFR TKI gefitinib [5] and cisplatin-based chemotherapy
[6, 7]. Although these studies permitted afatinib dosage
reductions to 20 mg daily for treatment-related adverse
events of grade 3 or higher (or prolonged grade 2 events),
clinical data regarding the efficacy of afatinib 20 mg daily
in NSCLC are limited.
We report our experience with a patient with advanced
EGFR-mutated NSCLC who achieved complete tumor
response with afatinib 20 mg daily, after intolerable
adverse events developed at higher afatinib dosages.
2 Case Report
A 71-year-old female was admitted to an emergency
department for dysphonia and dyspnea. The patient’s
medical history included hypertension and osteoarthritis;
she had never smoked. Total body computed tomography
(CT) imaging showed a thoracic mass in the superior left
lobe, with multiple small bilateral nodules and pleural
effusion (Fig. 1a), but was negative for abdominal, brain,
Fig. 1 Computed tomography (CT) imaging: a at diagnosis; b after
2 months of afatinib 40 mg daily showing partial tumor response;
c after 8 months of afatinib therapy showing further partial response
(dosage reduced to 30 mg daily); and d after 11 months of afatinib
R. Giusti et al.
or bone metastases. Based on bronchoscopy with biopsy
findings, the patient was diagnosed with EGFR-mutated
(Exon 21, L858R) NSCLC adenocarcinoma, cT4 N2 M0,
stage IV according to the American Joint Committee on
Cancer staging system, 7th edition [8]. The patient under-
went palliative thoracentesis to manage dyspnea, from
which cytology examination detected NSCLC cells. Sur-
gery was excluded because of bilateral lung metastases and
pericardial involvement. Considering the tumor histologi-
cal and biological features and the patient’s good Karnof-
sky Performance Status (KPS) score (70% at diagnosis),
first-line treatment with oral afatinib 40 mg daily was
initiated.
After 2 months of afatinib 40 mg daily, the patient
presented with several adverse events based on Common
Terminology Criteria for Adverse Events (4.03 version):
grade 3 skin rash (Fig. 2a, b), grade 3 mucositis, grade 2
diarrhea, and grade 2 paronychia. In accordance with
labeling information, afatinib therapy was interrupted and
the patient was admitted to the oncology department for
further treatment. During hospitalization, CT imaging
showed partial response to afatinib therapy (Fig. 1b). After
dermatologic consultation, the patient started intravenous
and topical antibiotic (amoxicillin/clavulanic acid) and
antimycotic (fluconazole) treatment, as well as topical 3%
boric acid solution. Ten days later, her skin rash and
mucositis had regressed to grade 2, with complete resolu-
tion of gastrointestinal toxicities.
Twenty days after treatment interruption, the patient
restarted afatinib therapy at a reduced dosage of 30 mg
daily. Eight months after starting afatinib therapy, CT
imaging showed further partial response compared with the
previous scan, with resolution of the pleural effusion and
therapy (dosage reduced to 20 mg daily) showing complete tumor
response. CT scans a and c were conducted with contrast, b was
performed at high resolution, and d is a low-dose CT scan of positron
emission tomography
Afatinib 20 mg Daily in Advanced EGFR-Mutated NSCLC

Fig. 2 a, b Grade 3 skin rash

developed after 2 months of
afatinib 40 mg daily with
macules/papules covering
[30% of body-surface area
with associated pain and
limiting self-care. c, d Complete
resolution of skin rash after
3 months of afatinib 20 mg
daily without local or systemic
recurrence of non-small cell
lung cancer

multiple bilateral lesions (Fig. 1c). The patient’s dysphonia

had also improved. However, she continued to present with
grade 2 skin rash with infected lesions. The afatinib dosage
was further reduced to 20 mg daily, and the patient started
empiric antibiotic treatment with oral doxycycline 100 mg
twice daily until toxicity improved to grade 1.
After 3 months of afatinib 20 mg daily (i.e., 11 months
after starting afatinib therapy), positron emission tomogra-
phy-CT imaging showed complete regression of the tumor
(Figs. 1d, 3). The patient’s dyspnea had completely recov-
ered and she had an estimated KPS of 80%. At this time, we
observed complete resolution of skin toxicity (grade 0,
Fig. 2c, d) and the patient reported only grade 1 diarrhea.
At last follow-up, the patient had no local or systemic
recurrence of disease and PFS was about 11 months.

3 Discussion

Patients with advanced NSCLC, if untreated, have an

estimated median survival of 4–5 months following diag- Fig. 3 Positron emission tomography imaging after 11 months of
nosis [9]. Historically, first-line treatment for NSCLC has afatinib therapy

been platinum-based chemotherapy, which provides a
modest improvement in survival but carries a high risk of
toxicity [9, 10]. In patients with EGFR-mutated NSCLC,
EGFR TKIs, such as afatinib, are superior to conventional
chemotherapy with respect to overall response, PFS, and
quality of life [10], and are recommended as first-line
therapy [11].
Diarrhea and skin-related toxicities with afatinib are
common and can often lead to dosage reduction or
treatment discontinuation. According to afatinib labeling
information, treatment should be interrupted for prolonged
or intolerable grade 2 diarrhea or skin-related events or
any adverse event of grade 3 or higher [2–4]. After the
adverse event has resolved or improved to grade 1, afa-
tinib can be resumed at a reduced dosage (i.e., 10 mg/day
lower), but should be permanently discontinued in patients
who experience unacceptable toxicities at 20 mg daily
[2–4].
In this case report of a patient with advanced EGFR-
mutated NSCLC, complete tumor response was
achieved with afatinib after the dosage was reduced to
20 mg daily for intolerable skin-related toxicities. At
the time of the patient’s first visit, final data on head-to-
head comparisons of afatinib versus gefitinib or erloti-
nib were not available. Treatment with afatinib was
initiated because its broad spectrum of activity and
irreversible mechanism of action had been postulated to
be associated with improved inhibition of EGFR-de-
pendent tumor growth compared with first-generation
EGFR TKIs. Furthermore, the availability of different
dosages allowed for better management of drug-related
adverse reactions.
Although data on the use of afatinib 20 mg daily are
limited, our observations are consistent with a previous
case report [12] and clinical study [13]. In the previous
case, afatinib 20 mg/day in combination with pred-
nisolone was associated with primary tumor size reduction
and improvement in carcinomatous lymphangitis in a
patient with NSCLC adenocarcinoma [12]. In a clinical
study of afatinib 40 mg daily [5], post-hoc analysis of 160
patients showed that 39% required dosage reduction to
30 mg daily and 13% had a further dosage reduction to
20 mg daily [13]. However, patients who received afatinib
at a reduced dose showed no significant difference in
median PFS and a reduction in the incidence and severity
of drug-related adverse events compared with those who
received 40 mg or higher. This suggests that dosing of
afatinib can be adjusted to help manage treatment-related
adverse events, without any apparent reduction in effi-
cacy. This may provide physicians and their patients with
confidence and allow physicians to better address adverse
events.
R. Giusti et al.
4 Conclusion
Low-dose afatinib may be effective in patients with EGFR-
mutated NSCLC who develop unacceptable toxicities at
higher dosages. Further studies investigating the efficacy of
afatinib 20 mg daily in EGFR-mutated NSCLC are
warranted.
Acknowledgements The authors would like to thank Sarah Greig,
PhD, of Springer Healthcare Communications who prepared the first
draft and provided formatting of the manuscript prior to submission.
This medical writing assistance was funded by Boehringer Ingelheim.
Compliance with Ethical Standards
Funding The authors have no sources of funding to disclose.
Conflicts of interest The authors have no conflicts of interest to
disclose.
Ethical approval All procedures were in accordance with the 1964
Helsinki Declaration (and its amendments). No approval by ethical
committee or institutional review board was required.
Informed consent Written informed consent was obtained from the
patient for publication of her case.
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