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P. Economopoulou
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MA 09 - The Current Status of Radiation Oncology (ID 666)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:Tomoki Kimura, Yong Chan Ahn
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 316
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MA 09.05 - Evidence in Favor of or against the Use of TKIs with Concurrent Cranial Radiotherapy in Patients with NSCLC and CNS Involvement (ID 8082)
11:30 - 11:35 | Author(s): P. Economopoulou
- Abstract
- Presentation
Background:
Central nervous system (CNS) metastases, including brain metastases (BM) and leptomeningeal metastases (LM) represent a frequent complication of non-small cell lung cancer (NSCLC). Patients with CNS metastases comprise a heterogeneous group, with a median survival that ranges from 3 to 14 months. Local therapies, such as whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS) or surgical resection, are available treatment strategies for BM. Introduction of tyrosine kinase inhibitors (TKIs) in clinical practice has led to individualization of therapy based upon the presence of the exact abnormality, resulting in a major therapeutic improvement in patients with NSCLC who harbor epidermal growth factor receptor (EGFR) activating mutations or anaplastic lymphoma kinase (ALK) gene rearrangements, respectively, but their role in combination with radiotherapy is controversial
Method:
We performed a systematic literature review of published data in PUBMED, SCOPUS and COCHRANE databases, as well as a manual search of reported data in major congresses, using the terms "EGFR-TKIs", "ALK-TKIs", "CNS", "BM" or ""LM" and "concurrent radiotherapy" or "stereotactic radiotherapy" from January 2000 through May 2017. Only prospective or retrospective clinical trials and meta-analyses reported in English language were included
Result:Author/year Phase No of pts EGFR status Treatment groups Control Outcomes Lind et al 2009 I 11 NA Cohort 1: Erlotinib 100 mg +WBRT Cohort 2: Erlotinib 150 mg +WBRT -Grade 3-5 toxicity in cohort 2 -High IDCR Welsh et al 2013 II 40 EGFR mutant: 9 of 15 pts tested Erlotinib 150 mg + WBRT -ORR 86%, -Median OS 11.8 m -Median OS 19.1 m in EGFR mutant Sperduto et al 2013 III 126 (closed early) NA Arm 2:TMZ+WBRT+ SRS Arm 3: Erlotinib 150 mg + WBRT+SRS Arm 1: WBRT +SRS OS not improved with addition of drugs -No difference in CNS-TTP between the three arms -49% grade 3-5 toxicity in arm 3 Lee et al.2014 II 80 EGFR mutant 1 out of 35 pts tested WBRT + Erlotinib WBRT No difference in OS Ma et al. 2009 II 21 NA WBRT +Gefitinib ORR 86% -Median OS 13 m -No significant grade 3 toxicity Pesce et al 2012 Randomized Phase II 59 NA WBRT + Gefitinib vs WBRT+ TMZ Median OS 6.3 m (Gefitinib arm), 4.9 m (TMZ arm) -No relevant toxicity Zeng et al 2012 Retrospective 90 NA WBRT +Gefitinib Gefitinib Higher ORR and OS with WBRT+ Gefitinib Luo et al 2015 Metaanalysis 980 (8 trials) NA Radiotherapy + TKI (TKI group) Radiotherapy or Radiotherapy+ chemotherapy (non-TKI group) -Higher RR, CNS-TTP and OS in radiotherapy +TKI group -No difference is serious AEs jiang et al 2016I Metaanalysis 1552 (15 trials) NA Radiotherapy + TKI Radiotherapy or Radiotherapy+ chemotherapy Higher RR, DCR, CNS-TTP and OS in radiotherapy +TKI group -Increased rate of any grade AEs
Conclusion:
At this time, concurrent use of TKIs with radiotherapy, although appearing to be safe, is not recommended outside of a clinical trial. Interestingly, data in EGFR mutant patients treated with an EGFR-TKI alone prompt the question whether this could be a front line approach in patients with asymptomatic BM, reserving WBRT for symptomatic cases. In clinical practice, burden of extracranial disease might also guide treatment decisions; physicians might select not to discontinue a TKI during WBRT in case of extensive extracranial organ involvement Ongoing clinical trials are currently evaluating the effectiveness of concomitant use of radiotherapy and TKIs.
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