NorthWest Biotherapeutics Inc (NWBO)

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I don't make the news, I just read it... " T.O. declares that he has no competing interest. D.M. is an inventor on patents related to gene and cell therapy,"
9. Conclusion
This dendritic vaccine trial has several limitations. These limitations include changing the primary endpoint (OS instead of PFS), creating a new study population (recurrent glioblastoma), conducting unplanned analyses, using external controls in a design originally intended to be randomized, all changes occurring years after the trial finished enrollment. The selected external controls likely included patients with less favorable outcomes, which opposes the “fit-for-purpose” criteria usually applied in selecting external controls. Therefore, the purported survival benefit from the vaccine is unreliable. The accumulation of limitations, along with multiple changes made over nearly two decades; further hamper the reliability of the reported results. Without data sharing, those concerns cannot be alleviated. Glioblastoma is the most common primary brain tumor, and there is no valid reason to stray from the gold standard of a randomized-controlled trial with overall survival as the primary endpoint in order to change clinical practice. Dendritic cell vaccination is a very promising approach for GBM, the neuro-oncology medical community can only regret that due to the described DCVax-L trial weaknesses, we cannot draw any conclusions on potential efficacy.

4. Removing PFS as the primary endpoint: no satisfactory explanation
The authors state that they removed PFS as the primary endpoint because estimates were unreliable due to pseudoprogression, which could occur in patients receiving the vaccine product. The modified Macdonald criteria, which cannot distinguish between true progression and pseudoprogression, were used. However, pseudoprogression had already been described before the study began, [8] and the RANO working group updated the criteria in 2010 to address the issue [9]. Considering that 91.5% of patients were enrolled between 2012 and 2015, accounting for pseudoprogression in the PFS assessment could have been done with an amendment before most participants were enrolled. Lastly, one could ask why it took almost 13 years after the first enrolled patient to decide PFS was no longer a valid endpoint in this trial, which would be a major deviation from the original design. We are concerned that changes in endpoints were made because PFS was ultimately negative.
https://www.sciencedirect.com/science/article/pii/S0035378723009190