Personal highlights of NSCLC therapy were the presentations of the IMpower 130 and 132 studies, both phase III investigating the combination of immunotherapy (atezolizumab) plus chemotherapy versus chemotherapy alone in the 1st
line therapy of advanced stage non-squamous NSCLC [1
]. Importantly, among IMpower 132 and 130 the chemotherapy backbone and maintenance strategy varies: IMpower 132 included in analogy to the KEYNOTE-189 [3
] study the combination of platinum/pemetrexed combined with atezolizumab versus platinum/pemetrexed alone and in the maintenance setting atezolizumab and pemetrexed were continued until disease progression versus pemetrexed alone maintenance. In contrast, IMpower 130 investigates the use of carboplatin/nab–paclitaxel plus atezolizumab (experimental arm) versus carboplatin/nab–paclitaxel alone and in the maintenance setting atezolizumab versus possible switch maintenance. Both studies showed a significant prolongation of progression-free survival (PFS; IMpower 132: PFS = 7.6 in combination chemotherapy/atezolizumab versus 5.2 months in chemotherapy alone; hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.49–0.72; p
< 0.0001; IMpower 130: PFS = 7.0 in combination chemotherapy/atezolizumab versus 5.5 months in chemotherapy alone; hazard ratio [HR] = 0.64, 95% CI: 0.54–0.77; p
< 0.0001). Furthermore the PFS benefit observed in IMpower 130 study translated to a significant prolongation of overall survival (OS; median OS was 18.6 months for the combinational arm compared with 13.9 months for the chemotherapy alone arm HR = 0.79; 95% CI, 0.64–0.98, p
= 0.033). While in the IMpower 132 only a numerical improvement of 4.5 months OS was observed, at this interim analysis statistical significance has not yet been met (median OS 18.1 versus 13.6 months; HR = 0.81, 95% CI: 0.64–1.03; p
= 0.0797). Updated OS data for the IMpower 132 will be presented in 2019.
In conclusion both studies highlighted that combinational therapy of chemotherapy and immunotherapy is the new standard of care in advanced stage NSCLC without driver alterations and these therapies were already incorporated into the most recent ESMO guidelines [4
]. The optimal therapeutic combination and predictive biomarker has not yet been identified; however PD-L1 expression crystallizes as the best biomarker at the moment. Furthermore in our opinion the maintenance strategy is an important issue in light of the IMpower 130 showing an OS benefit including a switch maintenance strategy to pemetrexed and in the experimental arm the continuation of atezolizumab. Therefore I think that however highly speculative also continuation with PD-1/PD-L1 maintenance monotherapy could be effective and opens the question if combinational maintenance therapy is necessary and hopefully these open questions will be answered at the next meetings this year.