EGFR ve ALK mutasyonu taşiyan akciğer adenokarsinomlarinda platin bazli tedavi yanitlari ve hedefe yönelik tedavi ihtiyacinin arka plani

Öz

Amaç: EGFR ve EML-4/ALK mutasyonlu akciğer adenokarsinomu hastalarındaki deneyimlerimizi sunmak. Gereç ve Yöntemler: 2580 hasta retrospektif olarak değerlendirildi. Çalışmaya yalnızca evre 4 akciğer adenokarsinomu olup ilk sıra en az 2 siklus platin bazlı rejimlerle tedavi edilen hastalar dahil edilmiştir. Bulgular: Çalışmaya uygun 105 vakanın 14’ü EGFR, 4’ü EML-4/ALK mutant iken 75 vaka her iki mutasyonu da taşımıyordu. Medyan yaş ve tanı yaşı sırasıyla 61 ve 58.5 idi. %81'i erkekti ve %78'i sigara içiyordu. EGFR ve EML-4/ALK-mutant hastalar ağırlıklı olarak kadındı ve sigara içmiyordu (sırasıyla EGFR; p=0.025 ve 0.002, EML-4/ALK; p=0.003 ve 0.012). EML-4/ALK- mutant hastalar, bu mutasyonu taşımayanlara göre daha gençti (p=0,02) (Tablo 1). EGFR ekson-19, 20 ve 21 mutasyonları sırasıyla karaciğer, kemik ve plevral metastazlarla ilişkiliydi (sırasıyla p=0.046, 0.05 ve 0.035). Birinci basamak platin bazlı kemoterapiden sonra tam remisyon ve kısmi yanıt oranları sırasıyla %4,7 ve %24,6 idi. Eşzamanlı radyoterapi ve tanı sırasında kemik metastazlarının olmaması birinci basamak platin bazlı tedavi yanıtlarını etkileyen faktörlerdi (sırasıyla p=0.004 ve p=0.046). EGFR veya EML-4/ALK mutasyon durumu platin bazlı tedavi yanıtı açısından anlamlı fark göstermemiştir (sırasıyla p=0,933 ve 0,184). Medyan progresyonsuz sağkalım 10 ay iken eşzamanlı radyoterapi ve kemik metastazının tedavi yanıtı üzerinde gözlenen etkisi PFS sonuçlarına yansımamıştır (sırasıyla p=0,079 ve 0,285). Sonuçlar: EGFR ve ALK mutasyonlarının varlığı, platin bazlı rejimlerin tedavi yanıtını etkilememektedir. EGFR ekson alt gruplarının metastaz noktaları ile ilişkisi araştırılması gereken bir nokta olarak saptanmıştır.

Anahtar Kelimeler

• EGFR
• EML-4/ALK
• ALK
• platin
• akciğer adenokarsinomu.

Background of the need for targeted therapy options and platinum-based therapy responses in EGFR and ALK-mutated lung adenocarcinoma

Öz

Aim: To present our experience in EGFR and EML-4/ALK-mutated lung adenocarcinoma patients. Material and Methods: 2580 patients were retrospectively evaluated. Only stage-4 lung adenocarcinoma patients who treated with at least 2-cycles of platinum-based regimens at frontline were included. Results: Among 105 eligible patients, EGFR and EML-4/ALK mutations was detected in 14 and 4 patients. 75 were wild- type for both mutations. The median age and age of diagnose was 61 and 58.5, respectively. 81% was male and 78% was smoker. EGFR and EML-4/ALK-mutant patients were predominantly female and non-smoker (EGFR; p=0.025 and 0.002, EML-4/ALK; p=0.003 and 0.012,respectively). EML-4/ALK- mutant patients were significantly younger than EML- 4/ALK wild-type (p=0.02) (Table 1). EGFR exon-19, 20 and 21 mutations were associated with liver, bone and pleural metastases, respectively (p=0.046, 0.05 and 0.035,respectively). After firstline platinum-based chemotherapy, complete remission (CR) and partial remission (PR) rates were 4.7% and 24.6%,respectively. Concurrent radiotherapy and absence of bone metastases at diagnosis were significant factors influencing firstline platinum-based therapy responses (p=0.004 and p=0.046,respectively). EGFR or EML-4/ALK mutation status didn’t show significant difference in terms of platinum- based treatment response (p=0.933 and 0.184,respectively). Median progression-free survival (PFS) was 10 months. The observed effect of concurrent radiotherapy and the presence of bone metastases on treatment response didn’t reflected in the PFS results (p=0.079 and 0.285,respectively). Conclusion: The presence of EGFR and ALK mutations does not effect the treatment response of platinum-based regimens. The association of EGFR exon subsets with metastasis points is worth investigating.

Anahtar Kelimeler

• EGFR
• EML-4/ALK
• ALK
• platinum
• lung adenocarcinoma

Kaynakça

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