HRQoL Maintained With Everolimus In Patients With Advanced Lung, Gastrointestinal NETs

In patients with unresectable, locally advanced or metastatic, nonfunctional neuroendocrine tumours of gastrointestinal or lung origin, overall health-related quality of life is preserved during treatment with everolimus

medwireNews: Treatment with the mammalian target of rapamycin inhibitor everolimus does not worsen health-related quality of life (HRQoL) relative to placebo in patients with advanced, nonfunctional, well-differentiated gastrointestinal or lung neuroendocrine tumours (NETs), suggests an analysis of the double-blind RADIANT-4 trial. 

“In view of the previous RADIANT-4 findings of longer progression-free survival [PFS] with everolimus , our findings suggest that everolimus delays disease progression while preserving overall HRQOL, even with the usual toxic effects related to active targeted drug treatment for cancer”, the investigators comment in The Lancet Oncology

The prespecified secondary endpoint of time to definitive deterioration – defined as a decrease of at least 7 points in the Functional Assessment of Cancer Therapy–General (FACT-G) total score – was comparable for the 205 participants randomly assigned to receive everolimus 10 mg/day and the 97 given placebo, occurring at a median of 11.27 and 9.23 months, respectively. 

In a post-hoc analysis, the median times to definitive deterioration in the FACT-G subscales (decrease ≥3 points) of physical, social and functional wellbeing were also similar for the everolimus- and placebo-treated patients. 

But interestingly, participants in the everolimus group had a significantly longer median time to definitive deterioration in the emotional wellbeing subscale than their counterparts in the placebo group, at 22.21 versus 17.64 months. 

A possible reason for this finding could be that “some patients assigned [to] everolimus might have had the perception of receiving treatment because of the presence of adverse events” or the improved PFS could have had a positive effect on emotional status, the team speculates. 

Of note, a higher proportion of everolimus- than placebo-treated patients were “quite a bit” or “very much” bothered by side effects at various timepoints, with ranges of 12–20% versus 2–6%, but “such level of discomfort did not produce significant differences in overall HRQOL”, write Simron Singh, from the Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada, and co-researchers. 

Commenting on the findings, Thomas Walter, from Hospices Civils de Lyon in France, reflects on the reasons for the comparable HRQoL between the study arms. 

One hypothesis is that “the toxic effects of everolimus are counterbalanced perfectly by its higher efficacy and potentially fewer disease-related symptoms than are reported with placebo”, he writes. 

But it is also possible that “we do not have good methods to assess small differences in HRQOL between treatments for NETs”, says the commentator, adding that study used a general questionnaire for cancer patients in the absence of a NET-specific tool adapted for nonfunctional tumours. 

Therefore, he concludes that “new simple methods to assess HRQOL, which take into account the specificities of this disease, are needed, but in the meantime a longer term assessment of HRQOL of patients with NETs might provide some important insight into the effectiveness of treatment.”  


Pavel ME, Singh S, Strosberg JR, et al. Health-related quality of life for everolimus versus placebo in patients with advanced, non-functional, well-differentiated gastrointestinal or lung neuroendocrine tumours (RADIANT-4): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol; Advance online publication 21 August 2017. doi:  

Walter T. Maintaining quality of life for patients with neuroendocrine tumours. Lancet Oncol; Advance online publication 21 August 2017. doi:  

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