Adding chemotherapy to gefitinib improves EGFR-mutated NSCLC outcomes
medwireNews: Supplementing the EGFR–tyrosine kinase inhibitor (TKI) gefitinib with pemetrexed and carboplatin doubles progression-free survival (PFS) in patients with advanced, chemotherapy-naïve non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations, according to phase III results.
As reported at the 2019 ASCO Annual Meeting in Chicago, Illinois, USA, median PFS was 16 months for the 176 participants with stage IIIB or IV disease who were randomly assigned to receive gefitinib 250 mg/day together with four cycles of pemetrexed 500 mg/m2 and carboplatin delivered to an area under the curve of 5 every 21 days, followed by pemetrexed maintenance.
This was significantly longer than the median PFS of 8 months for the 174 patients who received gefitinib alone, and equated to a significant reduction in the risk for progression or death of 49% with the combination regimen.
In addition, overall survival (OS) was also significantly improved with the combination of gefitinib and chemotherapy, with the median unreached versus 17 months for gefitinib alone, and a significant 55% decrease in the risk for death, reported Vanita Noronha, from the Tata Memorial Center in Mumbai, India.
She added that the gefitinib–chemotherapy regimen led to a “25% absolute increase” in the 18-month OS rate, rising to 78.3% from 48.7% with just gefitinib.
These improvements came on the back of significantly greater activity with the combination than gefitinib alone, with objective response rates of 75.3% and 62.5%, respectively.
However, the boost in survival with the combination came at the cost of more adverse events (AEs), with the presenter highlighting a significantly higher rate of all and clinically relevant toxicities of at least grade 3, at 75.0% versus 49.4% and 50.6% versus 25.3%, respectively.
This increase was primarily due to a significantly higher incidence of grade 3 or worse hematologic AEs in the combination than gefitinib group, she noted, adding that “the only other toxicities that were significantly higher in the combination arm included nephrotoxicity and hypokalemia.”
Putting their findings in context, Noronha remarked that to date most of the landmark trials comparing a TKI with either chemotherapy or another TKI have failed to show an OS benefit, making gefitinib plus pemetrexed and carboplatin “one of the only regimens that prolongs overall survival in EGFR-mutant NSCLC.”
And therefore this regimen “represents a new first-line therapy option” for these patients, she concluded.
By Catherine Booth
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