Frontline Tagrisso Improves Survival Among Specific Subgroup of Patients with NSCLC

First-line Tagrisso significantly extended overall survival compared with first generation EGFR-TKIs in patients with Ex19del/L858R EGFR mutated advanced non–small cell lung cancer, according to results from the phase 3 FLAURA study.
BY Kristie L. Kahl
PUBLISHED September 29, 2019
First-line Tagrisso (osimertinib) significantly extended overall survival compared with first generation EGFR-TKIs in patients with Ex19del/L858R EGFR mutated advanced non–small cell lung cancer (NSCLC), according to results from the phase 3 FLAURA study presented at the European Society of Medical Oncology (ESMO) Congress 2019 in Barcelona, Spain,

“The survival results are both statistically significant and clinically meaningful with first-line osimertinib for EGFR mutated patients,” study author Dr. Suresh Ramalingam, from Winship Cancer Institute of Emory University in Atlanta, said in a press release issued by ESMO. “This is the first time a TKI has proven to extend survival relative to another TKI in lung cancer therapy.”

Tagrisso, a third-generation, irreversible, oral EGFR-TKI that potently and selectively inhibits both EGFR-mutated and EGFR T790M resistance mutations, has previously demonstrated efficacy in NSCLC central nervous system metastases. Therefore, in the phase 3 trial, researchers evaluated Tagrisso, compared with older EGFR-TKIs, in 556 treatment-naïve patients with Ex19del/L858R EGFR-mutated advanced NSCLC.

Progression-free survival, or the time from first treatment to disease progression, served as the study’s primary endpoint and was previously reported on. Overall survival was the secondary endpoint.

Overall, 279 patients received 80 mg of oral Tagrisso once daily and 277 patients were treated with a comparator EGFR-TKI – either 250 mg of Iressa (gefitinib) on daily or 150 mg of Tarceva (erlotinib) once daily.

Crossover was allowed for 31% of patients in the comparator EGFR-TKI arm upon central confirmation of progression and T790M positivity. This represened 47% of patients in the control group that received post-study therapy. “That is consistent with what we would expect in the real-world setting, since only about 50% of patients develop the T790M mutation and will be candidates for osimertinib,” Ramalingam said.

The median overall survival with Tagrisso was 38.6 months versus 31.8 months with first generation EGFR-TKIs. Moreover, Moreover, 54% of patients in the Tagrisso arm were alive at three years, compared to 44% in the older generation EGFR-TKI arm.

The researchers noted that the safety profile appeared consistent with previously reported data.

“The results further reinforce the clinical utility and superiority of osimertinib in the front-line setting,” Ramalingam said. “Based on these data, osimertinib should be the preferred front-line therapy for EGFR-mutated lung cancer patients.”

Dr Pilar Garrido, from Ramón y Cajal University Hospital in Madrid, Spain, commented on the findings, noting that the magnitude of benefit in overall survival offers insight into what the best sequence of treatment is, given that Tagrisso is the only TKI approved for second-line treatment in patients who develop resistance due to T790M.

“If osimertinib is used as first-line therapy, there is no TKI available when the disease progresses,” she said. “Patients should be told that osimertinib offers an overall survival advantage and is well tolerated, but when the treatment fails, the only option is chemotherapy. Maximizing the duration of chemotherapy-free treatment is important for many patients, but if we want to know the most effective sequence of TKIs we need studies specifically designed for that.”
 
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