Substantially more patients in the docetaxel arm received subsequent immune checkpoint inhibitor (ICI) treatment than patients in the avelumab arm of the phase 3 JAVELIN Lung 200 study, which could have led to the trial’s failure to meet its primary end point, according to data from a post hoc analysis published in Lung Cancer.
Avelumab did not meet the primary end point of overall survival (OS) compared with docetaxel in patients with platinum-treated, PD-L1-expressing, non-small cell lung cancer (NSCLC). This post hoc analysis of the JAVELIN Lung 200 study (NCT02395172) evaluated whether ICI therapy administered after the study treatment affected OS.
In the open-label trial, JAVELIN Lung 200 investigators randomly assigned 729 adults with previously treated stage IIIB to stage IV or recurrent NSCLC to receive either avelumab or docetaxel. Secondary end points included progression-free survival (PFS). The post hoc analysis estimated the survival difference between the arms when the data were adjusted for subsequent ICI therapy.
In the PD-L1-positive population, 26.4% of patients in the docetaxel arm and 5.7% of patients in the avelumab arm received subsequent ICI therapy. “In all subgroups defined by PD-L1 expression, the proportion of patients receiving subsequent ICI in the docetaxel [arm] was consistently greater compared with the avelumab arm,” the investigators wrote.
OS was longer in patients who received subsequent ICI therapy compared with those who did not, regardless of random assignment to avelumab or docetaxel treatment during the study period. Among those who received subsequent ICI, the median OS was 19.4 months with docetaxel compared with 23.9 months with avelumab. In the subset of patients who did not receive a subsequent ICI, the median OS was 6.8 months with docetaxel vs 9.9 months with avelumab.
In the full analysis set, the median OS from the start of subsequent ICI therapy (ie, the start of third-line treatment) was 10.9 months and 10.7 months with avelumab and docetaxel, respectively.
Subsequent ICI use was also found to prolong PFS. Among ICI-receiving patients, the median PFS was 5.6 months with docetaxel and 6.9 months with avelumab. Patients who did not receive a subsequent ICI had a median OS of 3.2 months with docetaxel and 2.8 months with avelumab.
The study authors concluded that data from this post hoc analysis and other exploratory evaluations “support the hypothesis that the relatively high proportion of patients who received subsequent ICI in the docetaxel arm of JAVELIN Lung 200 may have confounded the OS outcomes in the study.”
They added that these results “highlight the potential impact of subsequent treatment in oncology trials, which has implications for study designs.”
Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.
Park K, Özgüroğlu M, Vansteenkiste J, et al. Impact of subsequent immune checkpoint inhibitor treatment on overall survival with avelumab vs docetaxel in platinum-treated advanced NSCLC: post hoc analyses from the phase 3 JAVELIN Lung 200 trial. Lung Cancer. Published online February 5, 2021. Doi:10.1016/j.lungcan.2021.01.026