An Amazing PFS with Icotinib in a Lung Adenocarcinomas Patient Harboring Rare Complex Gene Mutations: G719C/ S768I
Cai-hua Wang, Ting-ting Gu, Jie Zhang, Xiao-xiao Li and Jun-hong Jiang*
Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, China
Submission: November 16, 2018;Published: December 10, 2018
*Corresponding author: Jun-hong Jiang, Department of Respiratory Medicine of the First Affiliated Hospital of Soochow University, NO. 188 Shizi Street, Suzhou, Jiangsu 215006, China
How to cite this article: Cai-hua W, Ting-ting G, Jie Z, Xiao-xiao L, Jun-hong J. An Amazing PFS with Icotinib in a Lung Adenocarcinomas Patient Harboring Rare Complex Gene Mutations: G719C/ S768I. J Complement Med Alt Healthcare. 2018; 8(4): 555744. DOI:10.19080/JCMAH.2018.08.555744
Background and purpose: Nowadays, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) targeted therapy has developed to be the standard therapy for patients with advanced lung adenocarcinomas harboring common EGFR mutations. But the efficacy for the so-called rare and especially for the very rare complex EGFR mutations is not clear.
Methods: We describe a case of a 61-year-old male with advanced lung adenocarcinomas harboring rare complex EGFR mutations (G719C and S768I), and observe the clinical efficacy of icotinib, We discuss our case with other literatures.
Results: he has a good clinical response to icotinib. His progression-free survival (PFS) has reached to 36 months.
Conclusion: It may suggest that lung adenocarcinomas patients harboring rare complex gene mutations (G719C/ S768I) have relatively good efficacy and safety to icotinib.
Lung cancer is the leading cause of cancer related mortality worldwide and non-small cell lung cancer (NSCLC) represents 80% of all lung cancers. EGFR mutations are found approximately in 10% to 20% of the Caucasian population and from 30% to 60% of the Asian population with NSCLC . In recent years, EGFR-TKIs have improved to be the standard therapy for NSCLC with common EGFR mutations. However, the efficacy for rare complex EGFR mutations is not clear . We herein report a case of a patient with adenocarcinoma of the lung exhibiting two rare mutations, G719C in exon 18 and S768I in exon 20. He was treated with icotinib, and his PFS has reached to an amazing number (36 months).
A 61-year-old man with a 40-pack-year smoking history was admitted to our hospital in August 2015 because of an incidentally found mass in the lung. He underwent the right nephrectomy because of his right renal cyst in 2000. Physical examination revealed nothing of significance in the chest, abdominal regions, nor in the extremities. A computed tomography (CT) scan of the chest (Figure 1a) on 20, August 2015 revealed a 22-mm mass in the left lower lobe with multiple lung nodules in both lung fields without
mediastinal lymph nodes enlargement. Fiberoptic bronchoscopy was performed in our hospital. He was diagnosed advanced lung adenocarcinomas. He had two cycles of chemotherapy (pemetrexed 500mg/m2, day 1, oxaliplatin 130mg/m2, day 1). The levels of alanine aminotransferase (ALT, 174.5U/L) and aspartate aminotransferase (AST, 106.4U/L) in the serum were significantly increased within one month after the first cycle of chemotherapy. Fortunately, in his specimen of brush biopsy, rare complex EGFR mutations (G719C in exon 18 with abundance 11.65% and S768I in exon 20 with abundance 18.46%) were detected by the approach of next-generation sequencing. Then he received EGFR-tyrosine kinase inhibitor, gefitinib, as the second line treatment in a standard dose of 250 mg per day from October 2015. But he underwent severe diarrhea and serious hepatic damage, his levels of ALT, AST and serum creatinine (Scr) rose up to the highest peak (ALT 488U/L, AST 358U/L, Scr 157umol/L) after three weeks. Then his drug usage was stopped for about half a month and dose of 250 mg per day was reduced to 250mg every other day. Diarrhea and hepatic damage relieved half a month later. His chest CT (Figure 1b) on 28 November 2015, showed little smaller size in pulmonary lesion and multiple pulmonary nodules Then gefitinib was changed to icotinib in a standard dose of 150
mg three times a day from December 2015 and no diarrhea and
other complications occurred from then on. His levels of ALT and
AST went back to normal and a follow-up chest CT (Figure 1c) on
February 12, 2016, showed a decrease in tumor size as well as the
multiple pulmonary nodules. His chest CT (Figure 1d) on July 02,
2018, showed smaller size of the cancer and several nodules disappeared
without diarrhea or hepatic damage. Now the patient is
in good condition with follow-up.
Exon 19 deletions and L858R point mutations in exon 21,
are classical mutations, constituting 80-90% of EGFR mutations
. They are confirmed as sensitive mutations to EGFR-TKIs.
With the clinical application of more sensitive and precise tumor
genotyping systems, rare EGFR mutations, such as various point
mutations, insertions, and double mutants, are also frequently
encountered in routine clinical practice. S768I, a mutation in
exon 20, is one of those rare mutations and occurs approximately
1-2% in EGFR mutant of lung cancers . G719C is also a very
rare mutation in exon 18 of EGFR gene and is not often described
in literatures. Compound EGFR mutations, defined as double or
multiple independent mutations of the EGFR tyrosine kinase
domain, comprise 14% of all mutations identified during routine
sequencing of exons 18-21 of EGFR . But the rare compound
mutations with G719C and S768I are absolutely rare.
EGFR-TKIs have effective in the treatment of non-small cell
lung cancer with common EGFR mutations. Nowadays, Gefitinib,
erlotinib, afatinib and icotinib have been used in clinical practice.
But the relationship between rare EGFR mutations and sensitivity
to EGFR-TKI in NSCLC remains controversial. A retrospective
analysis by Baek et al.  reported that patients with rare or
complex mutations had inferior response and survival when treated
with EGFR-TKIs compared with patients harboring common EGFR
mutations. Chiu et al  indicated that the type of EGFR mutation
was an independent predictor of EGFR-TKI treatment response.
They proved patients with uncommon mutations had significant
shorter PFS (median, 7.7 vs 11.4 months; p < 0.001) and overall
survival (median, 17.2 vs 27.8 months; p<0.001) than that of
patients with common mutations.
By contrast, one prior clinical case of an EGFR S768I mutant
of lung adenocarcinoma reported apparent sensitivity to gefitinib
with a PFS more than 15 months . Hellmann et al.  reported a
case which provided conclusive evidence that EGFR S768I mutant
of lung adenocarcinomas was sensitive to erlotinib. Pasello et
al.  proved that afatinib seemed to be effective in rare and
complex mutations. Based on these findings, we hypothesized that
cases with different type of mutations had different response to
In our case, the patient harboring the rare mutations (G719C/
S768I) received gefitinib as the targed therapy, but severe diarrhea
and hepatic damage occurred. Then he started to take icotinib
and achieved stable disease and his PFS was 36 months. From
our case and literatures, it confirms that, the described complex EGFR mutations (G719C/ S768I) have relatively good sensitivity
to icotinib. It is expected that such rare complex mutations may be
more frequently detected with wider adoption of NGS-based tests.
More dedicated efforts are needed to clarify their biologic effects
on disease course and drug responsiveness.