Should the LAURA trial change our practice, and how? A PRO-CON debate!
Maintenance osimertinib in unresectable stage III EGFR-mutant cancer.
Today we tackle the LAURA trial. Out at ASCO and the NEJM.
The data from the LAURA trial have been presented at ASCO, and published the same day in the NEJM. The main result is an impressive benefit in progression-free survival in patients taking osimertinib as compared to those receiving placebo. The presentation even got a standing ovation, which is the new trend in oncology meetings. The median PFS was 5.6 months in the placebo group, and 39.1 months in the osimertinib group. Here, we provide PROs and CONs arguments that could be told to a patient.
PROs favoring the LAURA strategy
1) by not taking the pill, your risk of progression or death is massive (9 chance out of 10)
2) the progression can be local, can be distant and treated by the pill later, but it could also be a recurrence in the brain! No one wants a recurrence in the brain!
3) even if survival is not yet better, data are not mature and by not taking the pill right now, you take the risk of missing your chance of lowering your risk of death before the data are mature in the future!
4) the side effects are manageable. PS Side effects are always manageable*! (*according to the sponsor)
CONs against the LAURA strategy
1) in the LAURA trial, the placebo group underperformed compared to other data. A proportion of stage III unresectable lung cancer are deemed curable by chemoradiation alone, maybe 20, 30%? It is likely that a proportion of patients in LAURA were already metastatic, but they did not had proper staging with PET-CTs, and the metastases were likely missed. This could explain the very high rates of progression in those not taking osimertinib in LAURA.
2) we can monitor you closely, and treat you if and only if the disease progresses. Yes, the progression could be in the brain, but brain metastases can be treated. They are sometimes asymptomatic, only visible on brain MRI. And, by watching you closely, it is the only way to know if you will be among the fraction of patients that will never recur without any further treatment.
3) overall survival is not yet improved in the osimertinib group. Even if it’s shown to be improved in future analyses, we will have to make sure all patients that could have received osimertinib upon progression in the control arm actually received it. For now, the cross-over looks high, but we cannot exclude it could have been even higher.
4) side effects can be painful. Osi is a continuous treatment and 36% of patients in the osimertinib group got diarrhea. Even low grade diarrhea can impact your social life and quality of life. Grade 3 or higher adverse events were reported in 35% of patients taking the pill.
5) the cost of the pill is high, and we know it can affect many aspects of your life. Financial toxicity is a real concern.
Patients preferences and values
At the end of the day, patients may choose to receive osimertinib depending on many factors:
some will lean toward not taking any risk of progression or death, at any costs (including physical and financial toxicities).
others will lean at the other side of the spectrum, valuing the fact of being off-treatment, and trying all they can do to avoid receiving further treatment.
some will be on the middle, and their decision may be influenced by other factors, their age, having small children or not, having financial difficulties or not, etc.
Real shared-decision making takes time, and one needs to know the data. There is no unique roadmap that will apply to all patients. If you found this PRO-CON debate helpful, become a free or paid subscriber.