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

Year 2023, , 645 - 650, 30.09.2023
https://doi.org/10.18663/tjcl.1346853

Abstract

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.

References

  • Planchard D, Popat S, Kerr K et al. ESMO Guidelines Committee. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow- up. Ann Oncol. 2018 Oct 1;29(Suppl 4): iv192-iv237. doi: 10.1093/annonc/ mdy275. Erratum in: Ann Oncol. 2019 May;30(5):863-870. PMID: 30285222.
  • Cappuzzo F, Ligorio C, Toschi L et al. EGFR and HER2 gene copy number and response to first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). J Thorac Oncol. 2007 May;2(5):423-9. doi: 10.1097/01.JTO.0000268676.79872.9b. Erratum in: J Thorac Oncol. 2007 Jul;2(7):676. Ligorio, Claudio [corrected to Ligorio, Claudia]. PMID: 17473658.
  • Ettinger DS, Wood DE, Aisner D L et al. NCCN Guidelines® Insights: Non–Small Cell Lung Cancer, Version 2.2023: Featured Updates to the NCCN Guidelines. J Natl Compr Canc Netw., 21(4), 340-350.
  • M i t s u d o m i T, K o s a k a T, Ya t a b e Y. B i o l o g i c a l a n d c l i n i c a l i m p l i c a t i o n s o f EGFR mutations in lung cancer. Int J Clin Oncol. 2006 Jun;11(3):190- 8. doi: 10.1007/s10147- 006-0583-4. PMID: 16850125.
  • Schuette W, Schirmacher P, Eberhardt WE et al. EGFR mutation status and first-line treatment in patients with stage III/IV non-small cell lung cancer in Germany: an observational study. Cancer Epidemiol Biomarkers Prev. 2015 Aug;24(8):1254-61. doi: 10.1158/1055-9965. EPI-14-1149. Epub 2015 Jun 12. PMID: 26070531.
  • Yang P, Kulig K, Boland JM et al. Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma. J Thorac Oncol. 2012 Jan;7(1):90-7. doi: 10.1097/JTO.0b013e31823c5c32. PMID: 22134072; PMCID: PMC3931519.
  • Shaw AT, Yeap BY, Mino-Kenudson M et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol. 2009 Sep 10;27(26):4247-53. doi: 10.1200/JCO.2009.22.6993. Epub 2009 Aug 10. PMID: 19667264; PMCID: PMC2744268.
  • Kalikaki A, Koutsopoulos A, Hatzidaki D et al. Clinical outcome of patients with non- small cell lung cancer receiving front- line chemotherapy according to EGFR and K-RAS mutation status. Lung Cancer. 2010 Jul;69(1):110-5. doi: 10.1016/j. lungcan.2009.09.010. Epub 2009 Oct 24. PMID: 19854533.
  • Koh Y, Kim DW, Kim TM et al. Clinicopathologic characteristics and outcomes of patients with anaplastic lymphoma kinase- positive advanced pulmonary adenocarcinoma: suggestion for an effective screening strategy for these tumors. J Thorac Oncol. 2011 May;6(5):905-12. doi: 10.1097/JTO.0b013e3182111461. PMID: 21358343.
  • Camidge DR, Kim HR, Ahn MJ et al. Brigatinib versus Crizotinib in ALK-Positive Non- Small-Cell Lung Cancer. N Engl J Med. 2018 Nov 22;379(21):2027-2039. doi: 10.1056/NEJMoa1810171. Epub 2018 Sep 25. PMID: 30280657.
  • Ramalingam SS, Vansteenkiste J, Planchard D et al.; FLAURA Investigators. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. doi: 10.1056/NEJMoa1913662. Epub 2019 Nov 21. PMID: 31751012.
  • SEER*Stat Databases: November 2022 Submission [cited 2023 Aug 18]. Available from: https://seer.cancer.gov/statfacts/html/lungb.html
  • Wu M, Zhao J, Song SW et al. EGFR mutations are associated with prognosis but not with the response to front-line chemotherapy in the Chinese patients with advanced non- small cell lung cancer. Lung cancer. 2010; 67(3), 343-347. PMID: 19477549.
  • Dziadziuszko R, Holm B, Skov BG et al. Epidermal growth factor receptor gene copy number and protein level are not associated with outcome of non-small-cell lung cancer patients treated with chemotherapy. Ann Oncol. 2007;18(3), 447-452. PMID: 17082511.
  • Hotta K, Kiura K, Toyooka S et al. Clinical significance of epidermal growth factor receptor gene mutations on treatment outcome after first-line cytotoxic chemotherapy in Japanese patients with non-small cell lung cancer. J Thorac Oncol. 2007;2(7), 632-637. PMID: 17607119.

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

Year 2023, , 645 - 650, 30.09.2023
https://doi.org/10.18663/tjcl.1346853

Abstract

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.

References

  • Planchard D, Popat S, Kerr K et al. ESMO Guidelines Committee. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow- up. Ann Oncol. 2018 Oct 1;29(Suppl 4): iv192-iv237. doi: 10.1093/annonc/ mdy275. Erratum in: Ann Oncol. 2019 May;30(5):863-870. PMID: 30285222.
  • Cappuzzo F, Ligorio C, Toschi L et al. EGFR and HER2 gene copy number and response to first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). J Thorac Oncol. 2007 May;2(5):423-9. doi: 10.1097/01.JTO.0000268676.79872.9b. Erratum in: J Thorac Oncol. 2007 Jul;2(7):676. Ligorio, Claudio [corrected to Ligorio, Claudia]. PMID: 17473658.
  • Ettinger DS, Wood DE, Aisner D L et al. NCCN Guidelines® Insights: Non–Small Cell Lung Cancer, Version 2.2023: Featured Updates to the NCCN Guidelines. J Natl Compr Canc Netw., 21(4), 340-350.
  • M i t s u d o m i T, K o s a k a T, Ya t a b e Y. B i o l o g i c a l a n d c l i n i c a l i m p l i c a t i o n s o f EGFR mutations in lung cancer. Int J Clin Oncol. 2006 Jun;11(3):190- 8. doi: 10.1007/s10147- 006-0583-4. PMID: 16850125.
  • Schuette W, Schirmacher P, Eberhardt WE et al. EGFR mutation status and first-line treatment in patients with stage III/IV non-small cell lung cancer in Germany: an observational study. Cancer Epidemiol Biomarkers Prev. 2015 Aug;24(8):1254-61. doi: 10.1158/1055-9965. EPI-14-1149. Epub 2015 Jun 12. PMID: 26070531.
  • Yang P, Kulig K, Boland JM et al. Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma. J Thorac Oncol. 2012 Jan;7(1):90-7. doi: 10.1097/JTO.0b013e31823c5c32. PMID: 22134072; PMCID: PMC3931519.
  • Shaw AT, Yeap BY, Mino-Kenudson M et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol. 2009 Sep 10;27(26):4247-53. doi: 10.1200/JCO.2009.22.6993. Epub 2009 Aug 10. PMID: 19667264; PMCID: PMC2744268.
  • Kalikaki A, Koutsopoulos A, Hatzidaki D et al. Clinical outcome of patients with non- small cell lung cancer receiving front- line chemotherapy according to EGFR and K-RAS mutation status. Lung Cancer. 2010 Jul;69(1):110-5. doi: 10.1016/j. lungcan.2009.09.010. Epub 2009 Oct 24. PMID: 19854533.
  • Koh Y, Kim DW, Kim TM et al. Clinicopathologic characteristics and outcomes of patients with anaplastic lymphoma kinase- positive advanced pulmonary adenocarcinoma: suggestion for an effective screening strategy for these tumors. J Thorac Oncol. 2011 May;6(5):905-12. doi: 10.1097/JTO.0b013e3182111461. PMID: 21358343.
  • Camidge DR, Kim HR, Ahn MJ et al. Brigatinib versus Crizotinib in ALK-Positive Non- Small-Cell Lung Cancer. N Engl J Med. 2018 Nov 22;379(21):2027-2039. doi: 10.1056/NEJMoa1810171. Epub 2018 Sep 25. PMID: 30280657.
  • Ramalingam SS, Vansteenkiste J, Planchard D et al.; FLAURA Investigators. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. doi: 10.1056/NEJMoa1913662. Epub 2019 Nov 21. PMID: 31751012.
  • SEER*Stat Databases: November 2022 Submission [cited 2023 Aug 18]. Available from: https://seer.cancer.gov/statfacts/html/lungb.html
  • Wu M, Zhao J, Song SW et al. EGFR mutations are associated with prognosis but not with the response to front-line chemotherapy in the Chinese patients with advanced non- small cell lung cancer. Lung cancer. 2010; 67(3), 343-347. PMID: 19477549.
  • Dziadziuszko R, Holm B, Skov BG et al. Epidermal growth factor receptor gene copy number and protein level are not associated with outcome of non-small-cell lung cancer patients treated with chemotherapy. Ann Oncol. 2007;18(3), 447-452. PMID: 17082511.
  • Hotta K, Kiura K, Toyooka S et al. Clinical significance of epidermal growth factor receptor gene mutations on treatment outcome after first-line cytotoxic chemotherapy in Japanese patients with non-small cell lung cancer. J Thorac Oncol. 2007;2(7), 632-637. PMID: 17607119.
There are 15 citations in total.

Details

Primary Language English
Subjects Clinical Oncology, Cancer Genetics, Chemotherapy, Molecular Targets
Journal Section Research Article
Authors

Abdülkadir Erçalışkan 0000-0002-1795-5773

Zeynep Turna 0000-0003-0558-9371

Publication Date September 30, 2023
Published in Issue Year 2023

Cite

APA Erçalışkan, A., & Turna, Z. (2023). EGFR ve ALK mutasyonu taşiyan akciğer adenokarsinomlarinda platin bazli tedavi yanitlari ve hedefe yönelik tedavi ihtiyacinin arka plani. Turkish Journal of Clinics and Laboratory, 14(3), 645-650. https://doi.org/10.18663/tjcl.1346853
AMA Erçalışkan A, Turna Z. EGFR ve ALK mutasyonu taşiyan akciğer adenokarsinomlarinda platin bazli tedavi yanitlari ve hedefe yönelik tedavi ihtiyacinin arka plani. TJCL. September 2023;14(3):645-650. doi:10.18663/tjcl.1346853
Chicago Erçalışkan, Abdülkadir, and Zeynep Turna. “EGFR Ve ALK Mutasyonu taşiyan akciğer Adenokarsinomlarinda Platin Bazli Tedavi Yanitlari Ve Hedefe yönelik Tedavi Ihtiyacinin Arka Plani”. Turkish Journal of Clinics and Laboratory 14, no. 3 (September 2023): 645-50. https://doi.org/10.18663/tjcl.1346853.
EndNote Erçalışkan A, Turna Z (September 1, 2023) EGFR ve ALK mutasyonu taşiyan akciğer adenokarsinomlarinda platin bazli tedavi yanitlari ve hedefe yönelik tedavi ihtiyacinin arka plani. Turkish Journal of Clinics and Laboratory 14 3 645–650.
IEEE A. Erçalışkan and Z. Turna, “EGFR ve ALK mutasyonu taşiyan akciğer adenokarsinomlarinda platin bazli tedavi yanitlari ve hedefe yönelik tedavi ihtiyacinin arka plani”, TJCL, vol. 14, no. 3, pp. 645–650, 2023, doi: 10.18663/tjcl.1346853.
ISNAD Erçalışkan, Abdülkadir - Turna, Zeynep. “EGFR Ve ALK Mutasyonu taşiyan akciğer Adenokarsinomlarinda Platin Bazli Tedavi Yanitlari Ve Hedefe yönelik Tedavi Ihtiyacinin Arka Plani”. Turkish Journal of Clinics and Laboratory 14/3 (September 2023), 645-650. https://doi.org/10.18663/tjcl.1346853.
JAMA Erçalışkan A, Turna Z. EGFR ve ALK mutasyonu taşiyan akciğer adenokarsinomlarinda platin bazli tedavi yanitlari ve hedefe yönelik tedavi ihtiyacinin arka plani. TJCL. 2023;14:645–650.
MLA Erçalışkan, Abdülkadir and Zeynep Turna. “EGFR Ve ALK Mutasyonu taşiyan akciğer Adenokarsinomlarinda Platin Bazli Tedavi Yanitlari Ve Hedefe yönelik Tedavi Ihtiyacinin Arka Plani”. Turkish Journal of Clinics and Laboratory, vol. 14, no. 3, 2023, pp. 645-50, doi:10.18663/tjcl.1346853.
Vancouver Erçalışkan A, Turna Z. EGFR ve ALK mutasyonu taşiyan akciğer adenokarsinomlarinda platin bazli tedavi yanitlari ve hedefe yönelik tedavi ihtiyacinin arka plani. TJCL. 2023;14(3):645-50.


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