Metastatic NSCLC (Dr Riyaz Shah)
Result: Compared with placebo + chemotherapy, pembrolizumab + chemotherapy yielded superior overall survival (OS) and progression-free survival, higher objective response rate, durable response and generally expected toxicity in patients with non-squamous metastatic NSCLC. Health-related quality of life (HRQoL) in patients in the pembrolizumab arm was shown to maintain or improve compared with the placebo arm, despite a higher Grade 3–5 treatment-related adverse event rate.
KEYNOTE-407 PHASE III TRIAL (ABSTRACT 105)
Result: Similar results to KEYNOTE-189 have been reported for KEYNOTE-407, which compared combination pembrolizumab + chemotherapy with placebo + chemotherapy in patients with squamous metastatic NSCLC.
Interpretation: Practice-changing results have been reported for the KEYNOTE-189 and KEYNOTE-407 studies, particularly the OS results which showed dramatic improvements in the overall group and statistically significant improvement in all subgroups by programmed death-ligand 1 (PD-L1) status. The additional analysis on HRQoL for KEYNOTE-189 adds to the body of evidence that this treatment approach is applicable in clinical practice. Taken together, the results from KEYNOTE-189 and KEYNOTE-407 establish pembrolizumab + chemotherapy as the new standard of care for first-line treatment in NSCLC; although monotherapy with pembrolizumab has also shown excellent results in patients expressing high levels of PD-L1 (≥50%; KEYNOTE-024). The question yet to be answered by the data available is how to select between monotherapy or combination therapy with pembrolizumab – physicians are eagerly awaiting a rationale and resolution of this practice-changing query.
KEYNOTE-042 PHASE III TRIAL (ABSTRACT LBA4)
Result: Pembrolizumab monotherapy significantly improved OS in patients with squamous or non-squamous metastatic NSCLC compared with chemotherapy in ≥1%, ≥20% and ≥50% PD-L1 expression subgroups. Exploratory analysis of OS in patients with PD-L1 expression ≥1–49% reported a hazard ratio of 0.92 (95% confidence interval [CI]: 0.77–1.11).
Interpretation: While these results are positive as per the trial endpoints, the reporting of an upper CI which crosses 1 in the exploratory analysis of OS in patients with PD-L1 expression ≥1–49% indicates that the positive results seen for OS in the ≥1% and ≥20% subgroups are skewed by the result for the ≥50% subgroup. Dr Riyaz Shah indicated that this trial is negative in terms of clinical applicability and that current practice will remain unchanged.