Treatment of Advanced Non–small-cell Lung Cancer: a Fast Changing Paradigm

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P Teo

Hong Kong J Radiol 2012;15(Suppl):S64-71

Palliative chemotherapy and / or radiotherapy continue to represent the standard of care for patients with inoperable, advanced-stage non–small-cell lung cancer. However, histology and ‘driving’ mutations play an increasingly pertinent role in clinical decision-making in advanced non–small-cell lung cancer, with improved understanding of the molecular pathogenesis of lung cancer paving the way for tailored treatment in selected patient populations. This review describes pragmatic treatment paradigms for the first-line, maintenance, and second-line settings in advanced non–small-cell lung cancer. A key consideration in selecting a suitable treatment in the first-line setting is the presence of an actionable molecular pathway for which a specific targeted therapy is available. In the case of epidermal growth factor receptor–overexpressing tumours, treatment with an epidermal growth factor receptor–tyrosine kinase inhibitor such as erlotinib, gefitinib, or afatinib is a viable option. In patients without driving mutations, non-squamous disease can be treated with platinum-based chemotherapy plus pemetrexed with or without bevacizumab or cetuximab. Bevacizumab, in particular, is emerging as an effective option in both the first-line and maintenance settings. However, platinum-based chemotherapy that includes gemcitabine and docetaxel is preferred for squamous cell carcinomas. Failure after first-line chemotherapy with or without subsequent maintenance treatment requires a change to another targeted therapy or a change of chemotherapy. Second-line chemotherapy is currently offered to selected patients upon progression and may include pemetrexed for disease with non-squamous histology and docetaxel or erlotinib for all histological types. At present, only erlotinib is offered as a third-line option for unselected patients who have failed first- and secondline chemotherapy.





對於不能手術切除的非小細胞肺癌患者來說,紓緩性化療和/或放療仍然是標準的治理方法。然 而,病理組織和「驅動性」基因突變在晚期非小細胞肺癌的臨床決策中漸漸發揮重要作用,對肺癌 的分子發病機制更加了解可方便為個別患者進行針對性治療。本文探討晚期非小細胞肺癌實用的一 線、維持和二線治療。在進行一線治療時,是否存在一個有具體標靶治療的可行分子途徑是選擇合 適治療的一項重要考慮因素。對於有表皮生長因子受體(EGFR)過度表現的腫瘤,EGFR﹣酪胺酸 激酶抑制劑,如erlotinib、gefitinib或 afatinib是可行的選擇。在沒有「驅動性」基因突變的患者中, 非鱗狀細胞癌可以鉑類為基礎的化療加上pemetrexed(有或無bevacizumab或cetuximab)來治理。在一線和維持治療中,bevacizumab是一種新興而有效的選擇。然而,對於鱗狀細胞癌的患者,以包括 gemcitabine和docetaxel的鉑類為基礎的化療方案是可取的。無論有沒有後續的維持治療,如果一線化 療未見成效,便需改為進行另一種標靶治療或化療。如果患者病程惡化,便須進行二線化療,非鱗 狀癌的患者可以使用pemetrexed,而對於所有肺癌種類則可以使用docetaxel或erlotinib。目前,對於一 線和二線化療無效的患者來說,只有erlotinib可提供作為第三線治療。