EGFR mutasyonu veya ALK translokasyonu olan küçük hücreli dışı akciğer kanseri (KHDAK) tanılı hastaların klinik özelliklerinin ve yönetiminin incelenmesi: retrospektif gözlemsel çok merkezli vaka serisi çalışması

Yıl 2018, Cilt: 10 Sayı: 3, 361 - 367, 30.09.2018

Ali Murat Sedef , Züleyha Çalıkuşu , Yasemin Bakkal Temi Serkan Gökçay , Hüseyin Mertsoylu , Ali Ayberk Beşen Fatih Köse

https://doi.org/10.21601/ortadogutipdergisi.343275

Öz

Giriş:
Akciğer kanseri, kansere bağlı ölümlerin önde gelen nedenlerinden biridir.
Akciğer kanserinin en yaygın tipi Küçük hücreli dışı akciğer kanseri (KHDAK)
'dir. Moleküler hedefli ilaçlar, sürücü mutasyon içeren metastatik KHDAK'lı
hastaların tedavisinde kullanılır. Bu çalışmada, sürücü mutasyonu bulunan KHDAK
hastalarında birinci basamakta seçilen tedavi şekli, hasta özellikleri ve
sonuçları arasındaki ilişkiyi araştırmayı amaçladık.

Materyal-Metod:
Bu retrospektif çalışmayı, KHDAK hastalarında tirozin kinaz inhibitörlerinin kullanıldığı
tedavi basamağının sağkalım parametreleri ve hastalık prognozu üzerine etkisini
analiz etmek için tasarladık. Üç kanser merkezinden (Şanlıurfa Araştırma ve
Eğitim Hastanesi, Başkent Üniversitesi ve Acıbadem Mehmet Ali Aydınlar
Üniversitesi medikal onkoloji) sürücü mutasyonları bulunan 62 KHDAK hastasını
kayıt ettik

Sonuçlar:
Ortanca yaş 62 idi (aralık 30-81). EGFR mutasyonu ve EML4-ALK füzyon geni bulunan
sırasıyla 45 (% 71.4) ve 18 (% 28.6) hasta vardı. EGFR mutant 45 hastanın
22'sinde (% 34.9) ekson 19 delesyon vardı ve diğer 16 hastada (% 25.4) ekson 21
mutasyonu vardı. Ortanca genel sağkalım (OS) ve progresyonsuz sağkalım (PFS)
sırasıyla 31 ve 9 (% 95 CL, 5.4-12.6) ay idi. Tek değişkenli istatistiksel
analiz, EGFR mutasyonu pozitif ve FISH-ALK pozitif hastalar arasında OS ve PFS
açısından anlamlı farklılık göstermedi (p: 0.33). EGFR mutasyonu bulunan
hastalar arasında, ekson 19 delesyonu olan hastalarda sağkalım süresi, ekson 21
mutasyonları olanlara göre istatistiksel olarak anlamlı derecede yüksekti (p:
0.02). Oligometastatik hastaların genel sağkalım süresi diğer hastalardan
istatistiksel olarak anlamlı derecede yüksekti (p: 0.001). Birinci basamak
tedavide tirozin kinaz inhibitörü alan hastaların PFS'si birinci basamakta
kemoterapiyi kullanan hastalardan istatistiksel olarak anlamlı derecede
yüksekti. (14 ay vs 5 ay) (p: 0.01).

Tartışma: Bu çalışma, birinci basamak tedavide tirozin
kinaz inhibitörleri lehine tedavi tercihinin, sürücü mutasyonları olan
metastatik KHDAK hastalarında oldukça iyi sonuçlar verdiğini göstermiştir

Anahtar Kelimeler

Sürücü mutasyon, TKİ, KHDAK

Non-small-cell lung cancer (NSCLC) harboring driver mutation (EGFR mutation or ALK translocations) with clinical characteristics and management in a real-life setting: a retrospective observational multicenter case series study

Öz

Introduction: Lung
cancer is a leading cause of cancer-related mortality. The most common type of
lung cancer is Non-small-cell lung cancer (NSCLC). Molecular targeting drugs are
used in the treatment of patients with metastatic NSCLC who have a driver
mutation. In this study, we aimed to investigate the relationship between the
selected treatment modality in the first line setting, patients characteristics
and outcomes on NSCLC patients who had driver mutations.

Material
and Method: We designed this retrospective study to analyze
the effect of the treatment line of tyrosine kinase inhibitors on survival
parameters and disease prognosis in NSCLC patients. We enrolled 62 patients with
NSCLC who had driver mutations from three cancer centers; Şanlıurfa Research
and Training Hospital, Başkent University, and Acıbadem Mehmet Ali Aydınlar
University medical oncology departments.

Results: Median age
was 62 years old (range 30-81). There were 45 (71.4%) and 18 (28.6%) patients
with EGFR mutation and EML4-ALK fusion gene rearrangement, respectively. Out of
45 EGFR mutant patients, 22 (34.9%) patients had exon 19 deletion and other 16
(25.4%) patients had exon 21 mutation. Median overall survival (OS) and
progression free survival (PFS) was 31 and 9 (95% CI, 5.4-12.6) months, respectively. Univariate
statistical analysis failed to show significant difference between EGFR
mutation positive and FISH-ALK positive patients regarding OS and PFS (p:0.33).
Among patients with EGFR mutation, survival times for patients with exon 19
deletions were statistically significantly higher than those with exon 21
mutations (p:0.02). The overall survival time of oligometastatic patients was
statistically significantly higher than the other patients (p:0.001). The PFS
of patients who received tyrosine kinase inhibitor in first-line treatment was
statistically significantly higher than patients using chemotherapy in first
line setting. (14 months vs 5 months) (p:0.01)

Conclusion:
This study showed that treatment preference in favor of tyrosine kinase
inhibitors in first line setting produce fairly good outcomes in metastatic
NSCLC patients who had driver mutations.

Anahtar Kelimeler

Driver mutation, TKI, NSCLC

Kaynakça

• Reference 1: Detterbeck FC, Boffa DJ and Tanoue LT. The new lung cancer staging system. Chest 2009; 136: 260–271.
• Reference 2. Molina JR, Yang P, Cassivi SD, et al. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 2008; 83: 584–594.
• Reference 3: C.-H. Yang, C.-J. Yu, J.-Y. Shih, et al., Specific EGFR mutations predict treatment outcome of stage IIIB/IV patients with chemotherapy-naive non-small-cell lung cancer receiving first-Line gefitinib monotherapy, J. Clin. Oncol. 26 (16) (2008) 2745–2753.
• Reference 4: Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4- ALK fusion gene in non-small-cell lung cancer. Nature 2007; 448: 561-6. Reference 5. Rikova K, Guo A, Zeng Q, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 2007; 131: 1190-203.
• Reference 6: Benjamin J. Solomon, Tony Mok, Dong‑Wan Kimat al: First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer. N Engl J Med 2014;371:2167-77. DOI: 10.1056/NEJMoa1408440
• Reference 7: Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: Current standards and the promise of the future. Transl Lung Cancer Res. 2015;4:36–54. [PMC free article] [PubMed]
• Reference 8: Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002; 346:92-98
• Reference 9: Okamoto I, Mitsudomi T, Nakagawa K at al: The emerging role of epidermal growth factor receptor (EGFR) inhibitors in first-line treatment for patients with advanced non-small cell lung cancer positive for EGFR mutations. Ther Adv Med Oncol. 2010 Sep;2(5):301-7. doi: 10.1177/1758834010370698.
• Reference 10: Maemondo M, Inoue A, Kobayashi K at al: Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010 Jun 24;362(25):2380-8. doi: 10.1056/NEJMoa0909530.
• Reference 11: Cadranel J, Zalcman G, Sequist L at al: Genetic profiling and epidermal growth factor receptor-directed therapy in nonsmall cell lung cancer. Eur Respir J. 2011 Jan;37(1):183-93. doi: 10.1183/09031936.00179409. Epub 2010 Oct 28.
• Reference 12: Kim MH, Kim HR, Cho BC, et al. Impact of cigarette smoking on response to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in lung adenocarcinoma with activating EGFR mutations. Lung Cancer 2014; 84: 196–202.
• Reference 13: Riely GJ, Pao W, Pham D, et al. Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib. Clin Cancer Res 2006; 12: 839–844.
• Reference14: Jackman DM, Yeap BY, Sequist LV, et al. Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib. Clin Cancer Res 2006; 12: 3908–3914.
• Reference 15. Morita S, Okamoto I, Kobayashi K, et al. Combined survival analysis of prospective clinical trials of gefitinib for non-small cell lung cancer with EGFR mutations. Clin Cancer Res 2009; 15: 4493–4498.
• Reference 16. Yang CH, Yu CJ, Shih JY, et al. Specific EGFR mutations predict treatment outcome of stage IIIB/IV patients with chemotherapy-naive non-small-cell lung cancer receiving first-line gefitinib monotherapy. J Clin Oncol 2008; 26: 2745–2753.
• Reference 17. Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS).J Clin Oncol 2011; 29: 2866–2874.
• Reference18: Rusthoven KE, Hammerman SF, Kavanagh BD, et al. Is there a role for consolidative stereotactic body radiation therapy following first-line systemic therapy for metastatic lung cancer? A patterns-of-failure analysis. Acta Oncol 2009; 48:578.
• Reference 19: Parikh RB, Cronin AM, Kozono DE, et al. Definitive primary therapy in patients presenting with oligometastatic non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2014; 89:880.
• Reference 20: Albain KS, Crowley JJ, LeBlanc M, Livingston RB. Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest Oncology Group experience. J Clin Oncol 1991; 9:1618.