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V. Gebski



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    P1.08 - Poster Session 1 - Radiotherapy (ID 195)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P1.08-021 - Outcomes of Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer and Pulmonary Metastases. (ID 2578)

      09:30 - 09:30  |  Author(s): V. Gebski

      • Abstract

      Background
      Stereotactic ablative body radiotherapy (SABR) can achieve high local control rates in patients with Stage I non-small cell lung cancer (NSCLC) and pulmonary metastases. We report the outcomes of patients treated at Royal North Shore Hospital between January 2010 and January 2012.

      Methods
      Patients were discussed in a multi-disciplinary meeting and were medically inoperable, or refused surgery. Lesions were divided into central or peripheral zone lesions. Peripheral lesions received 48 Gy in 4 fractions, and central lesions 50 Gy in 5 fractions. Minimum coverage was 98% of the target to receive the prescribed dose. Treatment was delivered on a Varian Clinac with 7-10 field IMRT. Toxicity was graded according to CTC-AE version 4.0.

      Results
      Patient Characteristics Thirty-four lesions were treated in 27 patients. Eleven patients (41%) had Stage I NSCLC, 15 (56%) pulmonary metastases, and 1 patient presented with synchronous primary NSCLC and brain metastases. The commonest primary site for pulmonary metastases was colorectal cancer (n=6). The median age was 72 years. Sixty-seven percent (n=18) of patients were medically inoperable with the other patients refusing surgery. Radiotherapy Dosimetry Eighteen tumours received 48 Gy in 4 fractions, and 12 tumours received 50 Gy in 5 fractions. Three patients with multiple lesions received 18 Gy in 1 fraction to their third lesion. One patient, with a tumour adjacent to the brachial plexus, received 49 Gy in 7 fractions. Survival With a median follow-up period of 24 months, 4 patients with pulmonary metastases and 3 patients with primary NSCLC have died. In patients with pumonary metastases the first site of failure was distant in 5 patients and pulmonary in 5 patients, with 1 in-field recurrence. In NSCLC patients there were 4 pulmonary recurrences, 3 of these were in-field. Two patients have developed metastatic disease. The median time to first event was 18 months in NSCLC patients and 7 months in patients with pulmonary metastases. Figure 1 Toxicity Two patients developed grade 2 pneumonitis. Grade 1 chest, dyspnoea or cough were seen in 7 patients. No other toxicity was seen.

      Conclusion
      Our data support the increasing use of SABR lung as an effective and non-toxic treatment. However, there were a number of local recurrences in NSCLC patients occurring after 15 months, supporting the need for long-term follow-up. In patients with pulmonary metastases the median time to further disease progression was 7 months- more rigorous patient selection may help to identify patients in whom SABR lung will be most beneficial.

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    P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 2
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      P1.11-002 - Toxicity of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs) in the Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC): A Meta-analysis (ID 292)

      09:30 - 09:30  |  Author(s): V. Gebski

      • Abstract

      Background
      We performed a meta-analysis to evaluate the risk of toxic death, treatment discontinuation and grade 3 or 4 (G3/4) adverse events (AEs) of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of advanced non-small cell lung cancer (NSCLC).

      Methods
      Randomized trials comparing EGFR-TKI monotherapy or combination EGFR-TKI-chemotherapy with chemotherapy or placebo were included. We extracted data on toxicity events, and computed pooled relative risks (RR) adjusted for median treatment duration as the ratio of the risks in the EGFR-TKI arm versus the control group. Three treatment comparisons were analysed: EGFR-TKI versus placebo, EGFR-TKI versus chemotherapy, EGFR-TKI-chemotherapy versus chemotherapy. All statistical tests were two-sided.

      Results
      Thirty-five trials (16,507 patients) were included. EGFR-TKI was associated with 1.7% risk of toxic death (95% CI 1.4-2.0). Compared with EGFR-TKI, we demonstrated no difference in risk of toxic death for placebo (RR 1.15, 95% CI 0.08-1.86, p=0.86) or chemotherapy (RR 0.77, 95% CI 0.50–1.16, p=0.22), but higher risk for EGFR-TKI-chemotherapy compared to chemotherapy (RR 4.23, 95% CI 1.12-14.41, p=0.03). The risks of treatment-related discontinuation and G3/4 AEs were lower for EGFR-TKI than chemotherapy (RR 0.41, 95% CI 0.34-0.50, p<0.001; RR 0.35, 95% CI 0.32-0.38, p<0.001 respectively) but higher for EGFR-TKI than placebo (RR 2.43, 95% CI 1.73-3.40, p<0.001; RR 1.18, 95% CI 1.04-1.33, p=0.008) and for EGFR-TKI-chemotherapy than chemotherapy (RR 1.99, 95% CI 1.66-2.39, p<0.001; RR 1.50, 95%CI 1.32-1.70, p<0.001).

      Conclusion
      EGFR-TKI therapy in advanced NSCLC has a low incidence of toxic death and similar safety to chemotherapy with fewer serious AEs. Likelihood of benefit and careful consideration of toxicity profiles should inform treatment selection. Improved toxicity reporting in future trials would allow better quantification of EGFR-TKI-associated toxicity.

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      P1.11-003 - Exon 19 deletions, smoking history and gender as additional predictive factors for treatment benefit with EGFR Tyrosine Kinase Inhibitors in patients harbouring activating EGFR mutations: A Meta-analysis of 1432 patients in six randomised trials. (ID 1789)

      09:30 - 09:30  |  Author(s): V. Gebski

      • Abstract

      Background
      Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are now recognised as the standard first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harbouring activating EGFR mutations. Many studies consistently demonstrated superior tumour response and progression-free survival (PFS) over chemotherapy. However, there are still ongoing questions whether there are any significant differences in treatment outcomes between patients of different ethnicity, gender, age, performance status, smoking history, tumour histology and different subtypes of EGFR mutation. We performed a meta-analysis to assess the impact of these factors on the PFS benefit of EGFR-TKIs in advanced NSCLC patients harbouring activating EGFR mutations.

      Methods
      An electronic search of all randomised controlled trials comparing efficacy of first-line therapy of EGFR-TKI vs chemotherapy in advanced NSCLC patients harbouring EGFR mutation was performed. We extracted the published hazard ratio (HR) and the 95% confidence interval (CI) for PFS, if available, or obtained unpublished data, for subgroups defined by each factor. For each subgroup, pooled estimates of treatment efficacy of EGFR-TKI vs chemotherapy were calculated with the fixed-effects inverse variance weighted method. The predictive effect of each factor was analysed by a test for interaction between the factor and treatment effect; P<0.05 was considered statistically significant. All statistical tests were two-sided.

      Results
      We included 6 eligible studies, with two trials for each of these different EGFR-TKIs - Gefitinib, Erlotinib, and Afatinib – with a total of 1432 patients. As expected, overall the use of EGFR-TKIs in this mutated population significantly prolonged PFS as compared with chemotherapy (HR 0.37, 95% CI 0.32 to 0.43, P<0.001). While mutations at both Exon 19 (deletions) and at Exon 21 (L858R point mutations) were associated with significantly prolonged PFS, the benefit with Exon 19 mutations was greater: HR 0.26, 95% CI 0.21 to 0.31, P<0.001; as contrasted to Exon 21: HR 0.42, 95% CI 0.34 to 0.52, P<0.001 (treatment-EGFR mutation interaction P=0.001). Smoking status also showed differential benefit in this mutated population: never smokers: HR 0.30, 95% CI 0.26 to 0.36, P<0.001; contrasted to current or ex-smokers: HR 0.48, 95% CI 0.37 to 0.61, P<0.001; treatment-smoking history interaction P=0.003). There was also a trend for greater benefit for females with EGFR-TKI therapy as contrasted to males (HR [females] 0.32, 95% CI 0.27 to 0.38, P<0.001; HR [males] 0.42, 95% CI 0.33 to 0.53, P<0.001; treatment-gender interaction P=0.06). Interestingly, several parameters were not significant predictors of PFS benefit with EGFR-TKI treatment in this mutated population: performance status (ECOG 0 and 1 vs 2; interaction P=0.86); age (<65 vs ≥65 years; interaction P=0.58); ethnicity (Asian vs others; interaction P=0.18); and tumour histology (adenocarcinoma vs others; interaction P=0.52).

      Conclusion
      While EGFR-TKIs significantly prolong PFS in all advanced NSCLC patients harbouring classic activating EGFR mutations when compared with chemotherapy, other molecular and demographic factors have a further influence on benefit. Exon 19 deletions, never-smoking history, and possibly female gender were all associated with longer PFS in these patients when treated with EGFR-TKIs as compared with chemotherapy. These findings should enhance better trial design in future clinical trials.