Adagrasib improves on docetaxel in previously treated NSCLC

Dr Robert Jotte - Rocky Mountain Cancer Centers, Colorado

KRYSTAL-12 was a global study evaluating second-line therapy of an oral therapy, adagrasib, versus standard of care docetaxel, IV therapy; adagrasib being dosed an oral drug daily, versus docetaxel once every three weeks, in standard dosing 75mg/m2. It was a 450-patient study randomised 2:1 adagrasib to docetaxel evaluating primary progression free survival as well as overall survival although our data at this point is still immature as far as the overall survival data. But the trial did demonstrate improvement in progression free survival as well as improved response rates, almost more than tripled response rates compared to standard of care docetaxel.

Importantly, as well, is the response rates that we saw intracranially for patients that had metastatic disease to the brain. Just under 20 patients in both arms had metastatic disease to the brain but adagrasib, the oral therapy, demonstrating a 40% intracranial response which is fairly remarkable in this patient population.

So it definitely met its primary endpoint of the progression free survival although, of course, we’re eagerly awaiting the results of the overall survival.

Adagrasib is currently indicated in this setting and this data simply continues to support its utilisation. In this KRASG12C population of patients that have that mutation, this has clearly become a new standard of care for that patient population superseding the previous standard of care, docetaxel.

Anything else you would like to add?

Another important aspect of this trial that we need to await on the results of which in part will impact the overall survival is the fact that it was a trial that allowed patients on the docetaxel arm to cross over to the adagrasib arm. So that will be something that will need to be utilised as part of the interpretation of those results once they’re available.