Atezolizumab vs best supportive care in resected NSCLC

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Published: 9 Aug 2022
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Dr Enriqueta Felip - Vall d'Hebron University Hospital, Barcelona, Spain

Dr Enriqueta Felip speaks to ecancer upon her study of the overall survival interim analysis of a phase III study of atezolizumab vs best supportive care in resected NSCLC.

An interim analysis of overall survival data from the IMpower010 trial showed an overall survival trend in favour of atezolizumab in the PD-L1 TC > 1% stage II-IIIA population, but not in the all randomised stage II-IIIA or intent-to-treat population.

At the clinical cutoff date, the median follow-up was 45 months and 25% of patients had died. An overall survival trend in favour of atezolizumab was observed in the PD-L1 TC ≥1% stage II-IIIA population.

Adverse events of Grade 3-4 occurred in 22% of the atezolizumab arm and 11.5% of the best supportive care arm and led to atezolizumab discontinuation in 18.2% of patients.

Grade 5 treatment-related adverse events occurred in 0.8% of patients who received atezolizumab and 0% in the best supportive care arm.

Adverse events of special interest occurred in 52.1% of atezolizumab-treated patients, and 7.9% were in Grades 3-4.

 

IMpower010 is a trial in patients with early stage non-small cell lung cancer, including patients with stage 1b with tumour size of at least 4cm to 3a completely resected and according to the 7th TNM classification. The patients received the standard of care that is cisplatin-based chemotherapy, 1-4 cycles, and then 1,005 patients were randomised to receive atezolizumab for one year or best supportive care. The primary objective of this trial was disease free survival. In our trial the statistical design was a hierarchical one so first disease free survival in patients with stage 2 and 3a and PD-L1 positive tumours; if positive disease free survival in patients with stage 2 and 3a; if positive disease free survival in patients with stage 1b, 2 and 3a and if positive overall survival in patients with stage 1b, 2 and 3a.

We previously published the results of disease free survival in this trial in The Lancet last October. For patients with stage 2 and 3a and PD-L1 positive tumours atezolizumab improved disease free survival with a hazard ratio of 0.66. In patients with stage 2 and 3a including those with PD-L1 negative tumours atezolizumab improved disease free survival with a hazard ratio of 0.79. For the patients with stage 1b, 2 and 3a the hazard ratio was 0.81 and the statistical significance boundary was not crossed.

Today here we have presented the first pre-specified interim analysis for overall survival. This has been done with a median follow-up of the patients of 49 months and the data cut-off was April 2022. With this follow-up we have analysed and for those patients with stage 2 and 3 and PD-L1 positive tumours there was a trend towards an improvement in overall survival in those receiving atezolizumab. The hazard ratio was 0.71 for overall survival. This is a trend and the 95% confidence interval is between 0.85 to 1.03. 

Then we have analysed also for those patients with stage 2 and 3a together, including those patients with PD-L1 negative tumours there is no difference in overall survival between the two treatment arms. 

Finally when we analyse the patients with stage 1b, 2 and 3a, again irrespective of PD-L1, including those patients with PD-L1 negative tumours, there is no difference in overall survival. But, importantly for those patients with stage 2 and 3a and PD-L1 50% or higher, longer survival was observed with atezolizumab with a hazard ratio of 0.43. 

So we have also updated toxicity with this additional follow-up of 13 months and with this longer follow-up we have also observed that immunotherapy is well tolerated and there is not any difference, a very well tolerated agent in this setting.

So I think it’s important because for the first time we have presented a pre-specified interim analysis for overall survival. We know that it’s not the last one. So in these trials with early stage disease we need more than ten years to have mature results. But even in this first interim analysis for overall survival we have observed this trend in patients with stage 2 and 3a and PD-L1 positive tumours and also this hazard ratio of 0.43 for overall survival in the group of patients with stage 2 and 3a and PD-L1 50% or higher.

How can these results impact the future treatment of NSCLC?

It’s important to focus also in these patients with potentially curable disease. Immunotherapy is now part of the standard of care in patients with stage 4 disease but this study with the NADIM trial also presented and also the CheckMate 816, is helping also to introduce immunotherapy in these patients with non-metastatic disease.

In my opinion there is a need for testing also in patients with early stage disease. We need to test for EGFR mutation, ALK and PD-L1 and also it’s important, this group of investigators, the multidisciplinary team involving all groups of physicians treating these lung cancer malignancies in order to individualise each treatment in each patient. So it’s key, the multidisciplinary work, testing and also investigation.