The mix of osimertinib (Tagrisso, AstraZenca) plus chemotherapy is connected with ongoing advantages in formerly unattended innovative EGFR-altered non–small-cell lung cancer (NSCLC) even after illness development, according to a postprogression analysis of the FLAURA2 trial.
The outcomes, provided on March 21 at the European Lung Cancer Congress 2024 (Abstract4O), likewise recommend a possible general survival advantage with the addition of chemotherapy to the third-generation EGFR-tyrosine kinase inhibitor.
Offering the mix as first-line treatment “supplies long-lasting medically significant advantages beyond that seen for the preliminary progression-free survival,” stated research study speaker Natalia Isabel Valdiviezo Lama, MD, a medical oncologist from the National Institute of Neoplastic Diseases in Lima, Peru.
As formerly reportedby Medscape Medical Newsosimertinib was just recently authorized by the United States Food and Drug Administration in mix with platinum-based chemotherapy for first-line treatment of clients with EGFR-altered in your area advanced or metastatic NSCLC.
This approval was based upon arise from FLAURA2, which revealed that including platinum-based chemotherapy to osimertinib enhanced mean progression-free survival by 38%. At the time, the total survival information were immature however recommended an advantage with the mix compared to osimertinib alone.
The existing outcomes taken a look at postprogression results from FLAURA2 along with a 2nd interim total survival analysis.
The trial consisted of 557 advanced-NSCLC clients with EGFR exon 19 removals or exon 21 L858R anomalies who had actually gotten no previous systemic treatment. The clients might have likewise had steady main nerve system metastases and went through brain imaging at standard.
Research study individuals were arbitrarily appointed to osimertinib plus pemetrexed and carboplatin or cisplatinfollowed by upkeep osimertinib plus pemetrexed or osimertinib monotherapy up until radiologically specified illness development or other withdrawal requirements were satisfied.
The mix treatment was related to a longer time to second-line treatment at a mean of 30.7 months vs 25.4 months for osimertinib alone (threat ratio [HR]0.73).
There was likewise an enhancement in the time to third-line treatment with osimertinib plus chemotherapy, with the average not reached vs 33.2 months with osimertinib monotherapy (HR, 0.69).
The scientists kept in mind a distinction in the option of second-line treatment in between the 2 research study arms.
Of the 46% of clients in the mix group who began second-line treatment, 37% got a non– platinum-based chemotherapy and 32% got a platinum-based chemotherapy; 14% started an EGFR tyrosine kinase inhibitor aside from osimertinib.
In the osimertinib monotherapy arm, of the 60% of clients who started second-line treatment, 81% were offered a platinum-based chemotherapy, 3% were offered a non– platinum-based chemotherapy, and 7% were offered another EGFR tyrosine kinase inhibitor.
Even after beginning second-line treatment, clients in the osimertinib-plus-chemotherapy group continued to reveal an enhancement in results, with a mean 2nd progression-free survival of 30.6 months vs 27.8 months (HR, 0.70) with osimertinib monotherapy.
The 2nd interim total survival analysis exposed an “motivating pattern” in favor of the mix, stated Lama, after an average follow-up of roughly 31 months in both research study arms and an information maturity of 41%.
Far, the mean total survival has actually not been reached with osimertinib plus chemotherapy compared with 36.7 months in the osimertinib-alone group (HR, 0.75; P=.0280). This total survival advantage was seen throughout all prespecified subgroups.
Constant Benefit however More Toxicity
The magnitude of advantage seen with osimertinib plus chemotherapy remains in line with expectations provided the outcomes of previous mix treatment trials, stated Joop de Langen, MD, PhD, a thoracic oncologist at the Netherlands Cancer Institute in Amsterdam, who was not associated with the trial.
The results attained in the standard-of-care osimertinib monotherapy control arm, with roughly 60% of clients advancing after 2 years, reveal that there was “plainly space for enhancement.”
De Langen asked, is the advantage seen with this mix big enough to validate supplying it as first-line treatment for all our clients? The chemotherapy is “an [intravenous] treatment with cytotoxic negative effects, and clients need to go into the center every 3 weeks.”
He kept in mind that 64% clients in FLAURA2 who were offered osimertinib plus chemotherapy experienced any grade 3 or greater negative occasion compared to 27% in the osimertinib-alone arm, with most of occasions common of chemotherapy toxicity.
In addition, the progression-free survival information suggest that a large percentage of clients succeed with osimertinib alone, with 41% staying progression-free at 2 years, he included.
The outcomes reveal a constant advantage in favor of osimertinib plus chemotherapy, it comes “at the expense of extra toxicity,” de Langen stated.
“You can ask yourself whether these clients require to be treated with chemotherapy,” de Langen included. “Ideally, we would choose those clients in advance,” however that is tough based upon the presently offered information.
He recommended that the problem might be partly addressed by an approaching randomized trialin which clients with EGFR-altered NSCLC will be begun on 3 cycles of osimertinib then will go through distributing growth DNA screening.
The arise from this trial, stated de Langen, “may result in a more customized technique to stabilizing effectiveness and toxicity for each client that we see in our center.”
FLAURA2 was moneyed by AstraZeneca. Lama states no appropriate monetary relationships. Other authors state many monetary relationships, consisting of AstraZeneca, Merck Sharp & & Dohme, Bristol-Myers Squibb, Roche, Pfizer, Eisai, Sanofi, BeiGene, Chugai Pharmaceutical Co., Ltd., Takeda, Ono Pharmaceutical Co., Ltd., Novartis, Lilly, Amgen, Yuhan Pharmaceutical, Alpha Pharmaceuticals.
De Langen states relationships with AstraZeneca, BMA, Boehringer, Pfizer, Lilly, and MSD.