ESMO Asia 2015 News: Pembrolizumab ‘New Standard-Of-Care’ In Advanced NSCLC After Platinum-based Chemotherapy

The KEYNOTE-010 phase II/III trial supports the use of the immune checkpoint inhibitor pembrolizumab in advanced non-small-cell lung cancer patients

Compared with docetaxel, pembrolizumab significantly extends survival in previously treated patients with advanced non-small-cell lung cancer (NSCLC) positive for programmed death-ligand 1 (PD-L1), research shows.

The KEYNOTE-010 findings were presented at the European Society for Medical Oncology Asia 2015 Congress in Singapore and simultaneously published in The Lancet, with an accompanying commentary.

The phase II/III trial included 1034 patients with PD-L1–positive NSCLC who had progressed after at least two cycles of platinum-based chemotherapy. Study participants were randomly allocated to receive either pembrolizumab at a dose of 2 mg/kg or 10 mg/kg every three weeks or docetaxel 75 mg/m2 once in three weeks, with a respective 344, 346 and 343 patients in each group.

Median overall survival was significantly longer for the pembrolizumab 2 mg/kg and 10 mg/kg groups than for the docetaxel group. This was the case not only for patients harbouring tumours with PD-L1 expression of at least 50% (so-called tumour proportion score (TPS) of ≥50%), at 14.9 and 17.3 versus 8.2 months, respectively, but also for the total study population (TPS ≥1%), at 10.4 and 12.7 versus 8.5 months.

Both dosages of pembrolizumab also prolonged the co-primary endpoint of progression-free survival compared with docetaxel, but the differences were significant only for patients with a PD-L1 TPS of 50% or more (5.0 and 5.2 vs 4.1 months).

The objective response rate was significantly higher for participants given pembrolizumab 2 mg/kg or 10 mg/kg than for docetaxel-treated patients, both for patients with a TPS of at least 50% (30 and 29 vs 8%) and the total population (18 and 18 vs 9%).

Patients who received pembrolizumab experienced fewer treatment-related adverse events of grades 3–5 than those given docetaxel, at 13% in the low-dose arm, 16% in the high-dose arm and 35% in the docetaxel arm. And the rate of discontinuation due to side effects was also lower for both doses of pembrolizumab than docetaxel (4 and 5 vs 10%).

Roy Herbst, from Yale School of Medicine in New Haven, Connecticut, USA, reported that the incidence of immune-related toxicities was similar for the 2 mg/kg and 10 mg/kg groups – for instance, grade 3 or worse pneumonitis occurred in a respective 2.1% and 2.0% of patients and skin reactions in 0.9% and 1.7%.

He concluded that the data “support pembrolizumab as a new standard-of-care for advanced NSCLC that progressed on platinum-containing chemotherapy” and “validate the use of PD-L1 selection”.

The discussant Tony Mok, from The Chinese University of Hong Kong, drew attention to the key take-home messages from the trial.

First, as nearly a third of the participants had received two or more lines of systemic therapy, the positive findings confirmed the possibility of response in heavily pretreated patients and supported the use of pembrolizumab as second- or third-line treatment.

Second, the comparable efficacy and immune-related toxicity profiles of the low and high doses of pembrolizumab helped to define the optimum dose of the drug at 2 mg/kg every three weeks. Tony Mok commended the study authors for “aiming for the minimum effective dose”, but wondered whether an even lower dose would elicit similar outcomes.

Third, he noted that patients with PD-L1 levels of at least 50% and also those with levels between 1% and 49% derived a significant and moderate benefit, respectively, from pembrolizumab therapy. These findings together with those of the KEYNOTE-001 trial, which did not find a difference in survival outcomes between patients with a PD-L1 TPS of 1–49% and below 1%, begs the question: “Why should we test for PD-L1?”

And finally, the discussant admitted that the cost-effectiveness of immune checkpoint inhibitors is debatable and difficult to establish at present, especially without a robust biomarker.

Nevertheless, Tony Mok concluded that with these findings we are “almost ready” to integrate immune checkpoint inhibitors into the standard therapy algorithm for advanced stage NSCLC.


Herbst RS, Kim D-W, Felip E, et al. KEYNOTE-010: Phase 2/3 Study of Pembrolizumab (MK-3475) vs Docetaxel for PD-L1–Positive NSCLC After Platinum-Based Therapy. Presented at: ESMO Asia 2015 Congress. Singapore; 18–21 December 2015; LBA3 PR

Herbst RS, Baas P, Kim D-W, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 2015; Advance online publication 19 December

Mok TSK, Loong HH. Are we ready for immune checkpoint inhibitors for advanced non-small-cell lung cancer? Lancet 2015; Advance online publication 19 December