Nivolumab vs docetaxel updated results for nonsquamous, squamous NSCLC
medwireNews: Follow-up results from two trials of the programmed death 1 (PD-1) receptor inhibitor nivolumab versus docetaxel in patients with advanced non-small cell lung cancer (NSCLC) were reported at a proffered paper session held at the European Cancer Congress in Vienna, Austria.
Overall survival benefit confirmed for nivolumab in nonsquamous NSCLC
Updated overall survival (OS) data for the CheckMate 057 trial in patients with stage IIIb or IV nonsquamous NSCLC confirm the study’s initial finding that nivolumab offers significantly longer OS than docetaxel.
At 12 months, the median OS was 12.2 versus 9.5 months, with a 1-year OS rate of 51% versus 39%, reported Leora Horn, from Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, USA, at the meeting . The research was simultaneously published in The New England Journal of Medicine .
Median OS did not change by the 18-month checkpoint, at 12.2 versus 9.4 months and a significant hazard ratio of 0.72, and the overall rate of survival at 18 months was 39% versus 23%.Progression-free survival was comparable in the nivolumab and docetaxel groups but the researchers note that the survival curves crossed at 1 year, at rates of 19% and 8%, respectively, indicating a potential delayed benefit for nivolumab for this outcome.
Furthermore, patients given nivolumab had a higher objective response rate and a longer lasting treatment response than those given docetaxel, at 19% versus 12% and 17.2 versus 5.6 months, respectively. Indeed, nivolumab therapy achieved a higher response rate than docetaxel in all patient subgroups except for patients with tumours positive for EGFR mutations (11 vs 16%) and those who had never smoked (9 vs 15%).
When patients were stratified by programmed death-ligand 1 (PD-L1) expression, those with levels of 1% or more, 5% or more and 10% or more all had significantly better OS, progression-free survival and objective response rates than patients with lower PD-L1 expression.
Although there was no significant benefit for nivolumab over docetaxel for patients without PD-L1 expression, the PD-1 inhibitor was associated with a lower rate of grade 3 and 4 adverse events, at 5% versus 18% for the taxane. Patients given nivolumab were also less likely to discontinue treatment because of side effects, at 5% versus 15%.
“[T]he improved safety profile and durability of responses to nivolumab suggest that it might be a reasonable option for patients regardless of PD-L1 expression”, the authors therefore conclude.
Nivolumab improves QoL for squamous NSCLC
Martin Reck, from LungenClinic Grosshansdorf in Germany, presented overall health status results for the CheckMate 017 trial of nivolumab versus docetaxel in metastatic advanced squamous NSCLC.
The randomised phase III study has previously reported superior OS and progression-free survival for the PD-1 inhibitor over the taxane and comparable safety results, and there has been an indication of benefit with regard to symptom burden, as measured on the Lung Cancer Symptom Scale (LCSS).
Reck explained that the current presentation would focus on the exploratory quality of life (QoL) endpoints for patient-reported outcomes, as measured using the EuroQoL-5 Dimensions (EQ-5D) Utility Index and the EQ-5D visual analogue scale (VAS).
The patients were assessed at baseline and again every 3 or 4 weeks for 6 months, and every 6 weeks thereafter, plus at two post-treatment follow-ups, with comparable EQ-5D and LCSS completion rates for the two study arms.
EQ-5D Utility Index results showed that, compared with baseline, there was a “somewhat stable improvement” in QoL for nivolumab over 36 weeks versus worsening for docetaxel-treated patients. And this was “more pronounced” among long-term responders, over 60 weeks, although Reck emphasised that this result was “exploratory” in a “very limited” number of patients.
Nevertheless, he suggested that the EQ-5D utility index results indicate that nivolumab-treated patients’ QoL plateaued at a level comparable to that of general population norm, whereas the QoL of docetaxel patients was around that seen generally for lung cancer patients.
EQ-5D VAS results confirmed these QoL findings, Reck said.
Furthermore, time to first disease-related deterioration of QoL was also longer for the nivolumab-treated patients than the docetaxel group, with hazard ratios of 0.55 and 0.59 for the utility index and VAS scores, respectively.
The secondary endpoint of LCSS improvement at week 12 was achieved by around 20% of both patient groups by week 12 and time to deterioration of symptom burden over 2 years was comparable at this time point.
But over 60 weeks, there was a continuous reduction in symptom burden for nivolumab-treated patients compared with a worsening burden in those given docetaxel, and time to deterioration over 2 years measured on the LCSS 3-item index was also longer in the nivolumab arm with a significant hazard ratio of 0.57.
Reck therefore concluded: “Patients remaining on treatment with nivolumab returned to population health-status norm, suggesting that prolonged survival occurs with a resumption of normal life”, adding that these patients had a “meaningful improvement in mean symptom burden”.
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1. Horn L, Brahmer J, Reck M, et al. Phase 3, randomized trial (CheckMate 057) of nivolumab (NIVO) vs docetaxel (DOC) in advanced non-squamous (non-SQ) non-small cell lung cancer (NSCLC): Subgroup analyses and patient reported outcomes (PROs). Presented at: European Cancer Congress; Vienna, Austria: 25–29 September 2015; 3010
2. Borghaei H, Paz-Ares L, Horn L et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med; Advance online publication 27 September 2015
3. Reck M, Coon C, Taylor F, et al. Evaluation of overall health status in patients with advanced squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 017. Presented at: European Cancer Congress; Vienna, Austria: 25–29 September 2015; 3011