Antonio Passaro: The phase 3 KRYSTAL-12 trial represents a significant advancement in our understanding and treatment of KRAS-mutated NSCLC
Antonio Passaro, Medical Oncologist at European Institute of Oncology, shared a post on LinkedIn:
“Why is this Bristol Myers Squibb | Mirati Therapeutics press release on the phase 3 KRYSTAL-12 trial so crucial for our lung cancer community?
This collaborative effort marks a pivotal moment for our community. The phase 3 KRYSTAL-12 trial represents a significant advancement in our understanding and treatment of KRAS-mutated non-small cell lung cancer (NSCLC).
During ESMO20, the results of CodeBreak-200 were presented, later published in The Lancet, showcasing a noteworthy progression-free survival (PFS) improvement with sotorasib compared to docetaxel by just over a month: 5.6 vs. 4.5 months, with a hazard ratio (HR) of 0.66.
While these results mark a positive step forward, they have also left stakeholders perplexed, given the pressing therapeutic need for targeted anti-KRAS agents in clinical practice.
Following these results, the FDA Oncologic Drug Advisory Committee (ODAC) took a significant stance. They voted (10/2) that the PFS of sotorasib cannot be reliably interpreted versus docetaxel in this trial.
Instead of deliberating whether CodeBreak-200 should be utilized to transition accelerated approval to traditional approval for sotorasib, the committee focused on whether the primary endpoint of PFS per BICR (Blinded Independent Central Review) could be accurately interpreted in CodeBreak-200. Ultimately, the committee decided that the PFS could not be reliably interpreted, raising questions about the trial’s methodology and implications for future decision-making processes.
Despite the uncertainties surrounding sotorasib’s efficacy, it’s crucial to recognize the global disparity in access to direct KRAS p.G12C agents like sotorasib. The results of the KRYSTAL-12 study present a glimmer of hope for clinicians and patients worldwide. However, it’s important to note that initiating indirect comparisons versus sotorasib may not be currently fruitful, emphasizing the need for continued research and equitable access to innovative treatments.
We look forward to fully understanding the results of the KRYSTAL-12 study, potentially to be presented during ASCO24. This event could mark a turning point in the fight against lung cancer, offering new hope to NSCLC patients with KRAS mutations.”
Source: Antonio Passaro/LinkedIn