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Gabe Boldt
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EP1.14 - Targeted Therapy (ID 204)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.14-07 - Efficacy and Safety of ALK Inhibitors in ALK-Rearranged Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis (Now Available) (ID 785)
08:00 - 18:00 | Author(s): Gabe Boldt
- Abstract
Background
First and second generation ALK inhibitors were shown to delay disease progression and improve tumour response in ALK-rearranged advanced non-small cell lung cancer (NSCLC) patients. While a significant progression free survival (PFS) improvement has been consistently reported, no overall survival (OS) benefit was shown in randomized trials. We conducted a systematic review and meta-analysis to assess the efficacy and safety of ALK inhibitors compared to chemotherapy (ALK vs. chemo) and 2nd generation ALK inhibitors compared to 1st generation ALK inhibitors (ALK 2G vs. ALK 1G).
Method
The electronic databases PubMed and EMBASE, were searched for relevant randomized trials. Pooled hazard ratios (HR) for overall survival (OS) and progression free survival (PFS), and pooled risk ratios for objective response rates (ORR) and grade 3 or higher toxicity were meta-analyzed using the generic inverse variance and the Mantel-Haenszel methods. To account for between-studies heterogeneity, random-effect models were used. Subgroup analyses compared PFS by gender, smoking status, brain metastases, race and age.
Result
Six trials were included in the analysis of ALK vs. chemo and four in the analysis of ALK 2G vs. ALK 1G. Treatment with ALK inhibitors improved OS compared to chemotherapy (HR: 0.84, 95%CI 0.72-0.97) while a trend toward a better OS was seen with ALK 2G vs. ALK 1G without reaching statistical significance (HR: 0.64, 95%CI 0.36-1.16). PFS was improved with ALK vs. chemo and ALK 2G vs. ALK 1G (HR: 0.44, 95%CI 0.35-0.44 and HR: 0.38, 95%CI-0.29-0.51, respectively). Similarly, ORR was improved with ALK vs. chemo and ALK 2G vs. ALK 1G (RR: 2.68, 95%CI 1.89-3.81 and RR: 1.16, 95%CI 1.08-1.24, respectively). The risk of grade 3 or higher toxicity did not differ between treatments (RR 1.08, 95%CI 0.88-1.33 and RR 0.77, 95%CI 0.56-1.06, respectively). Overall the PFS benefit of ALK vs. chemo and ALK 2G vs. ALK 1G was homogenous across all subgroups with a greater degree of benefit within never-smokers when treated with ALK vs. chemo (p for subgroup differences=0.03).
Conclusion
This meta-analysis is the first, to our knowledge, to report an OS improvement with the use of ALK vs. chemo. A trend toward a better OS was also seen with ALK 2G vs. ALK 1G and this is likely because of crossover effects and limited OS follow-up. Longer follow up and further research are warranted to directly compare ALK inhibitor sequences and to understand the outcomes of 2nd generation ALK inhibitors as initial therapy.
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P1.17 - Treatment of Early Stage/Localized Disease (ID 188)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.17-21 - Safety and Effectiveness of Stereotactic Ablative Radiotherapy for Ultra-Central Lung Lesions: A Systematic Review (Now Available) (ID 1136)
09:45 - 18:00 | Author(s): Gabe Boldt
- Abstract
Background
The safety and effectiveness of stereotactic ablative radiotherapy (SABR) for patients with ultra-central lung tumours is currently unclear. We performed a systematic review to summarize existing data and identify trends in treatment-related toxicity and local control following SABR in patients with ultra-central lung lesions.
Method
We performed a systematic review using the PRISMA guidelines. The PubMed and Embase databases were queried from dates of inception until September 2018. Studies in the English language that reported treatment-related toxicity and local control outcomes post-SABR for patients with ultra-central lung lesions were included. Ultra-central lung lesions were defined as lesion whose gross tumour volume (GTV) or planning target volume (PTV) abutted or invaded the proximal tracheo-bronchial tree (PBT) or other mediastinal structures such as the great vessels or esophagus. Guidelines, reviews, non-peer reviewed correspondences, studies focused on re-irradiation and studies with fewer than 5 patients were excluded.
Result
A total of 446 studies were identified, with 10 meeting all criteria for inclusion. The total sample size from the identified studies was 250 patients with ultra-central lung lesions and all studies were retrospective in design. Six out of the 10 studies included a majority (>50%) of primary lung cancers. Radiotherapy dose and fractionation ranged from 30 to 60 Gy in 3 to 12 fractions, with biologically-effective doses (BED10) ranging from 48 to 138 Gy10 (median 78-103 Gy10). Median treatment-related grade >3 toxicity was 10% (range: 0-50%). Median treatment-related mortality was 5% (range: 0-22%), most commonly from pulmonary hemorrhage (55%). High-risk indicators for SABR-related mortality included gross endobronchial disease, maximum dose to the proximal bronchial tree (PBT) >180 Gy3 (BED3, corresponding to 45 Gy in 5 fractions or 55 Gy in 8 fractions), peri-SABR bevacizumab use, and antiplatelet/anticoagulant use. Median 1-year local control rate was 96% (range: 63-100%) and 2-year local control rate was 92% (range: 57-100%).
Conclusion
SABR for ultra-central lung lesions appears feasible and local control levels are comparable to those found in SABR for central lung lesions. There is a potential for severe toxicity in delivering SABR to ultra-central lung lesions especially in patients receiving high doses to the PBT, patients with endobronchial disease, and patients receiving bevacizumab or anticoagulants around the time of SABR. Prospective studies are required to establish the optimal doses, volumes and normal tissue tolerances for SABR in this patient population.
