‘Practice Changing’ Results for Osimertinib in Unresectable Stage III EGFR+ NSCLC

CHICAGO — Osimertinib (Tagrisso) may soon have approvals across all stages of epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer (NSCLC).

The third-generation EGFR tyrosine kinase inhibitor (TKI) already carries indications for metastatic disease and for adjuvant use in earlier-stage EGFR-mutated NSCLC.

Results from the phase 3 LAURA trial, presented at the American Society of Clinical Oncology (ASCO) annual meeting and funded by AstraZeneca, will likely lead to an approval for the remaining indication: Unresectable stage III disease.

Among patients randomized to either osimertinib or placebo following definitive chemoradiation, osimertinib extended median progression-free survival by 33.5 months compared with placebo — 39.1 vs 5.6 months, respectively (hazard ratio, 0.16; P = .001).

The news was greeted with a standing ovation at the meeting where it was presented by lead investigator and medical oncologist Suresh S. Ramalingam, MD, a lung cancer specialist at Emory University, Atlanta.

David R. Spigel, MD, a discussant on the trial, called the results “outstanding.”

“To have an 84% reduction in the risk of cancer progression or death is meaningful,” said Dr. Spigel, a medical oncologist at the Sarah Cannon Research Institute, Nashville, Tennessee, who reported ties to AstraZeneca. “This will be practice changing as soon as the label gets expanded.”

In the trial, investigators randomized 216 patients with unresectable stage III EGFR-mutated NSCLC who had not progressed after definitive platinum-based chemoradiation to receive either 80 mg osimertinib (n = 143) or placebo (n = 73). Baseline characteristics were generally balanced between the study arms, with a mostly even split between stage III subtypes.

Patients were staged by biopsy or CT at baseline plus MRI to confirm the absence of brain lesions. Subsequent imaging was repeated at regular intervals.

Twelve-month progression-free survival, assessed by blinded independent central review, was 74% with osimertinib vs 22% with placebo. At 24 months, the rates were 65% and 13%, respectively.

The progression-free survival benefit held across numerous subgroups but was statistically significant only among Asian individuals, who made up over 80% of both study arms.

Although the data are immature, osimertinib is also showing a trend toward improved overall survival, despite 81% of placebo patients crossing over to osimertinib after progression, Dr. Ramalingam reported. Mature overall survival results are expected within 2 years.

Based on these results, “osimertinib will become the new standard of care” after definitive chemoradiation in this patient population, Dr. Ramalingam said.

EGFR mutation testing “is now critical for stage III patients to ensure optimal” treatment, he added. Nearly a third of patients with NSCLC present with stage III disease, and the majority are unresectable. Of those, about a third are EGFR mutated.

Placebo was a fair comparator in the trial, Dr. Ramalingam stressed. While the current standard of care for unresectable stage III disease is 1 year of durvalumab after chemoradiation, durvalumab has proven ineffective in EGFR-mutated disease and often isn›t used in the setting.

If the control arm had been on durvalumab, patients would have needed to wait until it was safe to give them an EGFR TKI after progression, which didn’t seem to be in their best interest, he told this news organization.

A total of 68% of patients receiving placebo developed new lesions during the study, including brain metastases in 29%. New lesions developed in 22% of those on osimertinib, with new brain lesions in 8%.

The incidence of radiation pneumonitis, the most common adverse event, was 48% with osimertinib and 38% with placebo. Skin rash, diarrhea, and other known TKI side effects were also more common with osimertinib.

Treatment-related grade 3 or worse adverse events occurred in 13% of osimertinib patients vs 3% of placebo patients. Overall, 8% of osimertinib patients developed interstitial lung disease; most cases were low grade, but one person died.

About half of patients interrupted osimertinib dosing due to side effects, with a minority discontinuing.

Another study discussant, medical oncologist Lecia Sequist, MD, called the results “practice-changing” and said the findings support immediate consolidation with osimertinib instead of waiting for patients to progress.

Dr. Sequist, who reported ties to AstraZeneca, noted that patients were treated with osimertinib until progression, not for a limited duration as in past EGFR TKI trials, raising the possibility of indefinite, life-long treatment.

Treating until progression acknowledges the fact that for most patients, unresectable stage III NSCLC can’t be cured. However, she said a minority of patients might not need indefinite treatment — an important cohort to identify, given the drug costs more than $18,000 a month.

The study was funded by osimertinib maker AstraZeneca. Investigators included employees. Dr. Ramalingam, Dr. Spigel, and Dr. Sequist are advisers for and disclosed research funding from AstraZeneca. Dr. Spigel also disclosed travel funding.

A version of this article appeared on Medscape.com.

CHICAGO — Osimertinib (Tagrisso) may soon have approvals across all stages of epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer (NSCLC).

The third-generation EGFR tyrosine kinase inhibitor (TKI) already carries indications for metastatic disease and for adjuvant use in earlier-stage EGFR-mutated NSCLC.

Results from the phase 3 LAURA trial, presented at the American Society of Clinical Oncology (ASCO) annual meeting and funded by AstraZeneca, will likely lead to an approval for the remaining indication: Unresectable stage III disease.

Among patients randomized to either osimertinib or placebo following definitive chemoradiation, osimertinib extended median progression-free survival by 33.5 months compared with placebo — 39.1 vs 5.6 months, respectively (hazard ratio, 0.16; P = .001).

The news was greeted with a standing ovation at the meeting where it was presented by lead investigator and medical oncologist Suresh S. Ramalingam, MD, a lung cancer specialist at Emory University, Atlanta.

David R. Spigel, MD, a discussant on the trial, called the results “outstanding.”

“To have an 84% reduction in the risk of cancer progression or death is meaningful,” said Dr. Spigel, a medical oncologist at the Sarah Cannon Research Institute, Nashville, Tennessee, who reported ties to AstraZeneca. “This will be practice changing as soon as the label gets expanded.”

In the trial, investigators randomized 216 patients with unresectable stage III EGFR-mutated NSCLC who had not progressed after definitive platinum-based chemoradiation to receive either 80 mg osimertinib (n = 143) or placebo (n = 73). Baseline characteristics were generally balanced between the study arms, with a mostly even split between stage III subtypes.

Patients were staged by biopsy or CT at baseline plus MRI to confirm the absence of brain lesions. Subsequent imaging was repeated at regular intervals.

Twelve-month progression-free survival, assessed by blinded independent central review, was 74% with osimertinib vs 22% with placebo. At 24 months, the rates were 65% and 13%, respectively.

The progression-free survival benefit held across numerous subgroups but was statistically significant only among Asian individuals, who made up over 80% of both study arms.

Although the data are immature, osimertinib is also showing a trend toward improved overall survival, despite 81% of placebo patients crossing over to osimertinib after progression, Dr. Ramalingam reported. Mature overall survival results are expected within 2 years.

Based on these results, “osimertinib will become the new standard of care” after definitive chemoradiation in this patient population, Dr. Ramalingam said.

EGFR mutation testing “is now critical for stage III patients to ensure optimal” treatment, he added. Nearly a third of patients with NSCLC present with stage III disease, and the majority are unresectable. Of those, about a third are EGFR mutated.

Placebo was a fair comparator in the trial, Dr. Ramalingam stressed. While the current standard of care for unresectable stage III disease is 1 year of durvalumab after chemoradiation, durvalumab has proven ineffective in EGFR-mutated disease and often isn›t used in the setting.

If the control arm had been on durvalumab, patients would have needed to wait until it was safe to give them an EGFR TKI after progression, which didn’t seem to be in their best interest, he told this news organization.

A total of 68% of patients receiving placebo developed new lesions during the study, including brain metastases in 29%. New lesions developed in 22% of those on osimertinib, with new brain lesions in 8%.

The incidence of radiation pneumonitis, the most common adverse event, was 48% with osimertinib and 38% with placebo. Skin rash, diarrhea, and other known TKI side effects were also more common with osimertinib.

Treatment-related grade 3 or worse adverse events occurred in 13% of osimertinib patients vs 3% of placebo patients. Overall, 8% of osimertinib patients developed interstitial lung disease; most cases were low grade, but one person died.

About half of patients interrupted osimertinib dosing due to side effects, with a minority discontinuing.

Another study discussant, medical oncologist Lecia Sequist, MD, called the results “practice-changing” and said the findings support immediate consolidation with osimertinib instead of waiting for patients to progress.

Dr. Sequist, who reported ties to AstraZeneca, noted that patients were treated with osimertinib until progression, not for a limited duration as in past EGFR TKI trials, raising the possibility of indefinite, life-long treatment.

Treating until progression acknowledges the fact that for most patients, unresectable stage III NSCLC can’t be cured. However, she said a minority of patients might not need indefinite treatment — an important cohort to identify, given the drug costs more than $18,000 a month.

The study was funded by osimertinib maker AstraZeneca. Investigators included employees. Dr. Ramalingam, Dr. Spigel, and Dr. Sequist are advisers for and disclosed research funding from AstraZeneca. Dr. Spigel also disclosed travel funding.

A version of this article appeared on Medscape.com.

CHICAGO — Osimertinib (Tagrisso) may soon have approvals across all stages of epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer (NSCLC).

The third-generation EGFR tyrosine kinase inhibitor (TKI) already carries indications for metastatic disease and for adjuvant use in earlier-stage EGFR-mutated NSCLC.

Results from the phase 3 LAURA trial, presented at the American Society of Clinical Oncology (ASCO) annual meeting and funded by AstraZeneca, will likely lead to an approval for the remaining indication: Unresectable stage III disease.

Among patients randomized to either osimertinib or placebo following definitive chemoradiation, osimertinib extended median progression-free survival by 33.5 months compared with placebo — 39.1 vs 5.6 months, respectively (hazard ratio, 0.16; P = .001).

The news was greeted with a standing ovation at the meeting where it was presented by lead investigator and medical oncologist Suresh S. Ramalingam, MD, a lung cancer specialist at Emory University, Atlanta.

David R. Spigel, MD, a discussant on the trial, called the results “outstanding.”

“To have an 84% reduction in the risk of cancer progression or death is meaningful,” said Dr. Spigel, a medical oncologist at the Sarah Cannon Research Institute, Nashville, Tennessee, who reported ties to AstraZeneca. “This will be practice changing as soon as the label gets expanded.”

In the trial, investigators randomized 216 patients with unresectable stage III EGFR-mutated NSCLC who had not progressed after definitive platinum-based chemoradiation to receive either 80 mg osimertinib (n = 143) or placebo (n = 73). Baseline characteristics were generally balanced between the study arms, with a mostly even split between stage III subtypes.

Patients were staged by biopsy or CT at baseline plus MRI to confirm the absence of brain lesions. Subsequent imaging was repeated at regular intervals.

Twelve-month progression-free survival, assessed by blinded independent central review, was 74% with osimertinib vs 22% with placebo. At 24 months, the rates were 65% and 13%, respectively.

The progression-free survival benefit held across numerous subgroups but was statistically significant only among Asian individuals, who made up over 80% of both study arms.

Although the data are immature, osimertinib is also showing a trend toward improved overall survival, despite 81% of placebo patients crossing over to osimertinib after progression, Dr. Ramalingam reported. Mature overall survival results are expected within 2 years.

Based on these results, “osimertinib will become the new standard of care” after definitive chemoradiation in this patient population, Dr. Ramalingam said.

EGFR mutation testing “is now critical for stage III patients to ensure optimal” treatment, he added. Nearly a third of patients with NSCLC present with stage III disease, and the majority are unresectable. Of those, about a third are EGFR mutated.

Placebo was a fair comparator in the trial, Dr. Ramalingam stressed. While the current standard of care for unresectable stage III disease is 1 year of durvalumab after chemoradiation, durvalumab has proven ineffective in EGFR-mutated disease and often isn›t used in the setting.

If the control arm had been on durvalumab, patients would have needed to wait until it was safe to give them an EGFR TKI after progression, which didn’t seem to be in their best interest, he told this news organization.

A total of 68% of patients receiving placebo developed new lesions during the study, including brain metastases in 29%. New lesions developed in 22% of those on osimertinib, with new brain lesions in 8%.

The incidence of radiation pneumonitis, the most common adverse event, was 48% with osimertinib and 38% with placebo. Skin rash, diarrhea, and other known TKI side effects were also more common with osimertinib.

Treatment-related grade 3 or worse adverse events occurred in 13% of osimertinib patients vs 3% of placebo patients. Overall, 8% of osimertinib patients developed interstitial lung disease; most cases were low grade, but one person died.

About half of patients interrupted osimertinib dosing due to side effects, with a minority discontinuing.

Another study discussant, medical oncologist Lecia Sequist, MD, called the results “practice-changing” and said the findings support immediate consolidation with osimertinib instead of waiting for patients to progress.

Dr. Sequist, who reported ties to AstraZeneca, noted that patients were treated with osimertinib until progression, not for a limited duration as in past EGFR TKI trials, raising the possibility of indefinite, life-long treatment.

Treating until progression acknowledges the fact that for most patients, unresectable stage III NSCLC can’t be cured. However, she said a minority of patients might not need indefinite treatment — an important cohort to identify, given the drug costs more than $18,000 a month.

The study was funded by osimertinib maker AstraZeneca. Investigators included employees. Dr. Ramalingam, Dr. Spigel, and Dr. Sequist are advisers for and disclosed research funding from AstraZeneca. Dr. Spigel also disclosed travel funding.

A version of this article appeared on Medscape.com.