When should patients with advanced or metastatic non–small cell lung cancer receive osimertinib plus platinum-based chemotherapy in the frontline setting and when is osimertinib enough on its own?
That is a question brewing among some oncologists now that the US Food and Drug Administration has approved osimertinib (Tagrisso, AstraZeneca) for both indications in patients with epidermal growth factor receptor (EGFR) mutations.
An answer began to emerge in research presented on April 9, 2024, in San Diego at the American Association For Clinical Research Annual Meeting.
An exploratory analysis of the FLAURA2 trial found that, when patients have EGFR mutations on baseline circulating tumor DNA (ctDNA) testing, the combination treatment can extend progression-free survival (PFS). In this patient group, those receiving osimertinib alongside pemetrexed plus cisplatin or carboplatin had a 9-month PFS advantage compared with those who received osimertinib alone.
Conversely, when patients do not have EGFR mutations following baseline ctDNA testing, osimertinib alone appears to offer similar PFS outcomes to the combination therapy, but with less toxicity.
“Baseline detection of plasma EGFR mutations may identify a subgroup of patients who derive most benefit from the addition of platinum-pemetrexed to osimertinib as first-line treatment of EGFR-mutated advance non–small cell lung cancer,” investigator Pasi Janne, MD, PhD, a lung cancer oncologist at the Dana-Farber Cancer Institute, Boston, Massachusetts, said during his presentation of the exploratory analysis.
The FLAURA2 trial randomized 557 patients equally to daily osimertinib either alone or with pemetrexed plus cisplatin or carboplatin every 3 weeks for four cycles followed by pemetrexed every 3 weeks until disease progression or unacceptable toxicity.
Patients were tested for Ex19del or L858R EGFR mutations at baseline and at 3 and 6 weeks; baseline mutations were found in 73% of evaluable patients.
In patients with baseline mutations, the median PFS was 24.8 months with the combination therapy vs 13.9 months with osimertinib alone (hazard ratio [HR], 0.60).
In patients without baseline mutations, the median PFS was similar in both groups — 33.3 months with the combination vs 30.3 months with monotherapy (HR, 0.93; 95% CI, 0.51-1.72).
The investigators also found that having baseline mutations was associated with worse outcomes regardless of study arm, and mutation clearance was associated with improved outcomes. Clearance occurred more quickly among patients receiving the combination treatment, but almost 90% of patients in both arms cleared their mutations by week 6.
“As we move forward and think about which of our patients we would treat with the combination…the presence of baseline EGFR mutations in ctDNA may be one of the features that goes into the conversation,” Janne said.
Study discussant Marina Garassino, MD, a thoracic oncologist at the University of Chicago, Chicago, Illinois, agreed that this trial can help oncologists make this kind of treatment decision.
Patients with baseline EGFR mutations also tended to have larger tumors, more brain metastases, and worse performance scores; the combination therapy makes sense when such factors are present in patients with baseline EGFR mutations, Garassino said.
The wrinkle in the findings is that the study used digital droplet polymerase chain reaction (Biodesix) to test for EGFR mutations, which is not commonly used. Clinicians often use next-generation sequencing, which is less sensitive and can lead to false negatives.
It makes it difficult to know how to apply the findings to everyday practice, but Janne hopes a study will be done to correlate next-generation sequencing detection with outcomes.
The study was funded by AstraZeneca, maker of osimertinib, and researchers included AstraZeneca employees. Janne is a consultant for and reported research funding from the company. He is a co-inventor on an EGFR mutations patent. Garassino is also an AstraZeneca consultant and reported institutional financial interests in the company.
M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected]
Source link : https://www.medscape.com/viewarticle/osimertinib-better-alone-or-chemotherapy-nsclc-2024a10007sx?src=rss
Author :
Publish date : 2024-04-23 12:20:05
Copyright for syndicated content belongs to the linked Source.