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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- Key Points
cacious as first-line treatment in patients with EGFR-mu-
tated non-small cell lung cancer (NSCLC). Dosage The second-generation tyrosine kinase inhibitor
reduction is recommended in patients with intolerable afatinib, at 40 mg daily, effectively prolongs
adverse events; however, data regarding the efficacy of progression-free survival when used as first-line
low-dose afatinib are limited. We report the case of a therapy in patients with epidermal growth factor
71-year-old female patient who was diagnosed with (EGFR)-mutated non-small cell lung cancer
advanced EGFR-mutated NSCLC and started treatment (NSCLC).
with oral afatinib 40 mg daily. The patient achieved partial
tumor response on computed tomography imaging, but Afatinib is often associated with adverse events,
developed unacceptable skin-related toxicities requiring including skin rash, diarrhea, and stomatitis, that
dosage reduction to 20 mg daily. The patient subsequently may require dosage reduction.
achieved complete tumor response and showed improve- Although randomized clinical studies with afatinib
ments in performance status. These observations suggest have permitted dosage reductions for adverse events
that low-dose afatinib is effective in patients with EGFR- to 20 mg daily, clinical data regarding the efficacy of
mutated NSCLC who require dosage reduction for intol- afatinib 20 mg daily in NSCLC are limited.
erable adverse events.
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

& Raffaele Giusti Afatinib is a second-generation, irreversible inhibitor of


raffaelegiusti@yahoo.it; rgiusti@ospedalesantandrea.it epidermal growth factor receptor (EGFR) [1], and is
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 mutated non-small cell lung cancer (NSCLC) [2–4]. As
R. Giusti et al.

with other EGFR tyrosine kinase inhibitors (TKIs), the or bone metastases. Based on bronchoscopy with biopsy
most common adverse events with afatinib are diarrhea, findings, the patient was diagnosed with EGFR-mutated
skin rash, paronychia, and stomatitis. The grade and the (Exon 21, L858R) NSCLC adenocarcinoma, cT4 N2 M0,
severity of drug toxicity can lead to dosage reduction or stage IV according to the American Joint Committee on
permanent treatment discontinuation. According to label- Cancer staging system, 7th edition [8]. The patient under-
ing recommendations, the starting dosage of afatinib went palliative thoracentesis to manage dyspnea, from
should be 40 mg daily, although dosage reduction to 30 or which cytology examination detected NSCLC cells. Sur-
20 mg daily is possible if treatment is not tolerated [2–4]. gery was excluded because of bilateral lung metastases and
In the first-line treatment of EGFR-mutated NSCLC, pericardial involvement. Considering the tumor histologi-
randomized clinical studies have demonstrated the superior cal and biological features and the patient’s good Karnof-
efficacy of afatinib 40 mg daily in prolonging progression- sky Performance Status (KPS) score (70% at diagnosis),
free survival (PFS) compared with the first-generation first-line treatment with oral afatinib 40 mg daily was
EGFR TKI gefitinib [5] and cisplatin-based chemotherapy initiated.
[6, 7]. Although these studies permitted afatinib dosage After 2 months of afatinib 40 mg daily, the patient
reductions to 20 mg daily for treatment-related adverse presented with several adverse events based on Common
events of grade 3 or higher (or prolonged grade 2 events), Terminology Criteria for Adverse Events (4.03 version):
clinical data regarding the efficacy of afatinib 20 mg daily grade 3 skin rash (Fig. 2a, b), grade 3 mucositis, grade 2
in NSCLC are limited. diarrhea, and grade 2 paronychia. In accordance with
We report our experience with a patient with advanced labeling information, afatinib therapy was interrupted and
EGFR-mutated NSCLC who achieved complete tumor the patient was admitted to the oncology department for
response with afatinib 20 mg daily, after intolerable further treatment. During hospitalization, CT imaging
adverse events developed at higher afatinib dosages. showed partial response to afatinib therapy (Fig. 1b). After
dermatologic consultation, the patient started intravenous
and topical antibiotic (amoxicillin/clavulanic acid) and
2 Case Report antimycotic (fluconazole) treatment, as well as topical 3%
boric acid solution. Ten days later, her skin rash and
A 71-year-old female was admitted to an emergency mucositis had regressed to grade 2, with complete resolu-
department for dysphonia and dyspnea. The patient’s tion of gastrointestinal toxicities.
medical history included hypertension and osteoarthritis; Twenty days after treatment interruption, the patient
she had never smoked. Total body computed tomography restarted afatinib therapy at a reduced dosage of 30 mg
(CT) imaging showed a thoracic mass in the superior left daily. Eight months after starting afatinib therapy, CT
lobe, with multiple small bilateral nodules and pleural imaging showed further partial response compared with the
effusion (Fig. 1a), but was negative for abdominal, brain, previous scan, with resolution of the pleural effusion and

Fig. 1 Computed tomography (CT) imaging: a at diagnosis; b after therapy (dosage reduced to 20 mg daily) showing complete tumor
2 months of afatinib 40 mg daily showing partial tumor response; response. CT scans a and c were conducted with contrast, b was
c after 8 months of afatinib therapy showing further partial response performed at high resolution, and d is a low-dose CT scan of positron
(dosage reduced to 30 mg daily); and d after 11 months of afatinib 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
R. Giusti et al.

been platinum-based chemotherapy, which provides a 4 Conclusion


modest improvement in survival but carries a high risk of
toxicity [9, 10]. In patients with EGFR-mutated NSCLC, Low-dose afatinib may be effective in patients with EGFR-
EGFR TKIs, such as afatinib, are superior to conventional mutated NSCLC who develop unacceptable toxicities at
chemotherapy with respect to overall response, PFS, and higher dosages. Further studies investigating the efficacy of
quality of life [10], and are recommended as first-line afatinib 20 mg daily in EGFR-mutated NSCLC are
therapy [11]. warranted.
Diarrhea and skin-related toxicities with afatinib are
common and can often lead to dosage reduction or Acknowledgements The authors would like to thank Sarah Greig,
PhD, of Springer Healthcare Communications who prepared the first
treatment discontinuation. According to afatinib labeling
draft and provided formatting of the manuscript prior to submission.
information, treatment should be interrupted for prolonged This medical writing assistance was funded by Boehringer Ingelheim.
or intolerable grade 2 diarrhea or skin-related events or
any adverse event of grade 3 or higher [2–4]. After the Compliance with Ethical Standards
adverse event has resolved or improved to grade 1, afa-
Funding The authors have no sources of funding to disclose.
tinib can be resumed at a reduced dosage (i.e., 10 mg/day
lower), but should be permanently discontinued in patients Conflicts of interest The authors have no conflicts of interest to
who experience unacceptable toxicities at 20 mg daily disclose.
[2–4].
Ethical approval All procedures were in accordance with the 1964
In this case report of a patient with advanced EGFR- Helsinki Declaration (and its amendments). No approval by ethical
mutated NSCLC, complete tumor response was committee or institutional review board was required.
achieved with afatinib after the dosage was reduced to
20 mg daily for intolerable skin-related toxicities. At Informed consent Written informed consent was obtained from the
patient for publication of her case.
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
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