Highlights from

World Conference on Lung Cancer

19th annual meeting

Toronto, Canada 23-26 September 2018

Avelumab vs docetaxel for previously treated advanced non-small-cell lung cancer

The multinational, phase 3 JAVELIN Lung 200 trial investigated the PD-L1 antibody avelumab vs docetaxel in patients with advanced NSCLC after failure of platinum-based treatment. Outcomes showed that avelumab had a favourable safety profile but did not improve OS in patients with platinum-treated PD-L1 positive NSCLC. Eligible patients were ≥18 years old and had stage 3B/4 or recurrent NSCLC with disease progression after platinum doublet therapy. Between April 2015 and February 2017, 792 patients were randomised to avelumab (10 mg/kg Q2W) or docetaxel (75 mg/m2 Q3W). Randomisation was stratified by PD-L1 status (PD-L1+/PD-L1-) and histology (squamous/non-squamous).

Of these patients, 264 in the avelumab arm and 265 in in the docetaxel arm had PD-L1+ tumours. In this group, there was no significant difference in median OS between the treatment arms (11.4 vs 10.3 months; HR 0.90; one-sided P=0.16). OS findings may have been confounded by subsequent checkpoint inhibitor therapy in the docetaxel arm (26% vs 6% in the avelumab arm). Pre-planned exploratory analyses based on higher PD-L1 cut-offs found increased OS with avelumab vs docetaxel. The PD-L1 high subgroup (≥80% cut-off) included 29% of patients. Their OS was 17.1 months for avelumab vs 9.3 months for docetaxel (HR 0.59; two-sided P=0.0022). The PD-L1- medium/high subgroup group (≥50% cut-off) included 40% of patients. Their OS was 13.6 vs 9.2 months (HR 0.67; two-sided P=0.0052) (Figure 11). Post-hoc analysis also showed a trend for longer OS for avelumab in the squamous NSCLC population.

[Figure 11] Overall survival in medium and high PD-L1 subgroups (pre-planned analyses)

WCLC 2018: Figure 11 Overall survival in medium and high PD-L1 subgroups

The ORR in the PD-L1+ (≥1% cut-off) population was 18.9% in the avelumab-treated group vs 11.7% in the docetaxel arm (OR 1.76; one-sided P=0.0105). Median duration of response (DoR) was not reached for avelumab. It was 6.9 months with docetaxel (95% CI 3.5-not established).

Rates of treatment-related AEs were lower with avelumab than docetaxel for all grades (63.9% vs 85.8%) and grade ≥3 (9.9% vs 49.3%). Immune-related AEs occurred in 16.5% of patients treated with avelumab; 2.8% of patients had grade ≥3 AEs. Treatment-related deaths occurred in 1% of patients treated with avelumab vs 4% of those in the docetaxel group. Several trials of avelumab are ongoing in patients with NSCLC, including a phase 3 trial of avelumab monotherapy as first-line treatment for PD-L1+ NSCLC (JAVELIN Lung 100; NCT02576574).

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The content and interpretation of these conference highlights are the views and comments of the speakers/authors.