Data from Advances in Precision Cancer Care - Curated by EPG Health - Last updated 23 October 2018

Sunday’s ESMO 2018 report comes from Presidential Symposium 2, moderated by Fortunato Ciardiello (Napoli, IT) and Josep Tabernero (Barcelona, ES). Here, we share key data and discussions from presentations on the STAMPEDE trial, looking at the role of prostate radiotherapy for patients with newly diagnosed metastatic prostate cancer and JAVELIN Renal 101, assessing avelumab plus axitinib as a first-line treatment option for patients with advanced renal cell carcinoma. 

Scroll down for key insights from each presentation.

LBA5_PR - Radiotherapy (RT) to the primary tumour for men with newly-diagnosed metastatic prostate cancer (PCa): Survival results from STAMPEDE (NCT00268476)

Today, Dr Parker presented survival data from the STAMPEDE trial, considering the role of prostate radiotherapy for patients with newly diagnosed metastatic prostate cancer.

In this study, patients with newly diagnosed metastatic disease were randomised in a 1:1 ratio to standard androgen-deprivation therapy (ADT) +/- docetaxel or the same treatment plus radiotherapy to the primary tumour (36 Gy/6 fractions/6 weeks or 55 Gy/20 fractions/4 weeks). The primary endpoint of the study was OS. 

2,061 patients were randomised. Of these, approximately 42% had low metastatic burden, as defined by no visceral metastases or <4 bone metastases, and the majority (82%) received docetaxel concurrently with ADT. 

The 3-year failure-free survival was 23% in the standard arm and 32% in the investigational arm (HR 0.76, p<0.001). No difference, however, was observed in 3-year OS (62% in the standard arm and 65% in the investigational arm, HR 0.92, p<0.266). Of note, a subgroup analysis showed the radiotherapy schedule (decided before randomisation) did not influence the survival outcome (interaction p value 0.27). 

On the other hand, adding primary tumour radiotherapy to standard therapy was associated with a significant OS improvement in patients with low metastatic tumour burden but not in those with high metastatic tumour burden (interaction p value 0.0098). In the former group, 3-year OS was 73% in the standard arm and 81% in the investigational arm, HR 0.68, p<0.007). No statistically significant difference was observed between treatment arms for time to first symptomatic local event or time to CTCAE grade ≥3 AE. 

Dr Parker concluded radiotherapy to the prostate should be considered a standard treatment option for patients with newly diagnosed metastatic prostate cancer and low tumour burden. He also suggested this strategy should be investigated in other tumour settings.  

LBA6_PR - JAVELIN Renal 101: a randomized, phase 3 study of avelumab + axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC)

Dr Motzer presented results from JAVELIN Renal 101, a randomised phase III study comparing avelumab plus axitinib with single agent sunitinib as first-line treatment for patients with advanced renal cell carcinoma. 

In a previous phase Ib trial, combining the anti-PD-L1 monoclonal antibody, avelumab and the TKI, axitinib showed a favourable safety profile and promising objective response rate, supporting the hypothesis behind simultaneous inhibition of the VEGF/VEGFR and PD-1/PD-L1 pathways. The JAVELIN Renal 101 trial addressed the question, ‘could this combination be superior to standard first line therapy?’.

In this study, patients with treatment-naive advanced RCC, measurable disease and tissue availability for PD-L1 testing were randomised in a 1:1 ratio to avelumab plus axitinib or sunitinib. The co-primary endpoints were PFS (as per central radiological assessment) and OS in patients with PD-L1 positive tumours. 886 patients were randomised, of which 63% had PD-L1 positive tumours. Baseline patient characteristics were well balanced across treatment groups in the general population and the PD-L1 positive group. 

The primary endpoint of PFS was met. Median PFS was 13.8 months in the investigational arm and 7.2 months in the control arm (HR 0.61, p<0.0001). A similar improvement was observed in the overall [PD-L1 unselected] population (median PFS was 13.8 months in the investigational arm and 8.4 months in the control arm (HR 0.69, p=0.0001)). These results did not differ when PFS was measured according to the local investigator assessment and were also consistent across patient subgroups. 

A significant improvement with combination treatment was also seen using objective response rate and did not appear to be affected by PD-L1 expression (51–55% in the investigational arm vs 26% in the standard arm). Regarding OS, median OS was not reached in either arm, suggesting data are immature. Nevertheless, a trend towards an improvement in OS was observed, in favour of combination treatment (HR 0.78, p=0679). 

Interestingly, combination treatment was not associated with an increased risk of treatment-related AEs. Grade ≥3 treatment-related AEs occurred in 4% of patients in the investigational arm and 7% in the control arm. Only 1% of patients experienced an immune-related grade ≥3 AE. 

Dr Motzer concluded that, in view of the improvements to PFS and objective response rate, plus a good safety profile, avelumab plus axitinib should be considered a new first-line treatment option for unselected patients with advanced RCC.  

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