Efficacy observed for stage IB-IIIA disease

Patients with resectable stage IB to III non-small-cell lung cancer who undergo adjuvant therapy with osimertinib, which targets the epidermal growth factor receptor (EGFR), were significantly more likely to be alive and disease free at 2 years than those randomized to placebo post-surgery.

That finding from the 682-patient ADAURA trial was reported at the European Society for Medical Oncology (ESMO) virtual congress and simultaneously published online by The New England Journal of Medicine.

“At 24 months, 90% of the patients with stage II to IIIA disease in the osimertinib group (95% confidence interval [CI], 84-93) and 44% of those in the placebo group (95% CI, 37-51) were alive and disease-free (overall hazard ratio for disease recurrence or death, 0.17; 99.06% CI, 0.11-0.26; P<0.001),” wrote Yi-Long Wu, MD, of the Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, and Guangdong Academy of Medical Sciences, in Guangzhou, China, and colleagues.

Looking at the entire ADAURA population—stages IB to IIIA—89% of the patients in the osimertinib group (95% CI, 85 to 92) and 52% of those in the placebo group (95% CI, 46 to 58) were alive and disease-free at 24 months (overall hazard ratio for disease recurrence or death, 0.20; 99.12% CI, 0.14 to 0.30; P<0.001). At 24 months, 98% of the patients in the osimertinib group (95% CI, 95 to 99) and 85% of those in the placebo group (95% CI, 80 to 89) were alive and did not have central nervous system disease (overall hazard ratio for disease recurrence or death, 0.18; 95% CI, 0.10 to 0.33).”

At this time, overall survival data are not yet mature, but “29 patients died (9 in the osimertinib group and 20 in the placebo group).”

Wu and colleagues noted that the current standard postoperative adjuvant therapy recommendation is cisplatin-based chemotherapy, but that therapy “is associated with only a 16% decrease in the risk of disease recurrence or death at 5 years,” and just a 5% decrease in risk of death at 5 years. Moreover, the 5 year follow-up data with or without postoperative chemotherapy are disappointing: for stage IB patients the risk of disease recurrence is about 45% and that jumps to 76% for those with stage III disease.

The ADAURA researchers enrolled patients with completely resected EGFR mutation positive NSCLC from November 2015 through February 2019. They randomized 339 to osimertinib (80 mg once daily) and 343 placebo for 3 years. Prior to randomization, standard adjuvant chemotherapy was allowed. “Most patients with stage II to IIIA disease (76%) and approximately a quarter of the patients with stage IB disease (26%) received adjuvant platinum-based chemotherapy,” they wrote. Radiation therapy, pre or postoperative, was not allowed.

Among the findings:

  • At 24 months 26 of stage II or IIIA patients in the osimertinib group (11% maturity) had disease recurrence or death.
  • At 24 months 130 of stage II or IIIA patients in the control group (55% maturity) had disease recurrence or death.
  • Median disease-free survival was not reached (95% CI, could not be calculated to could not be calculated) in the osimertinib group.
  • Median disease-free survival was 27.5 months (95% CI, 22.0-35.0) in the placebo group.

The benefit of osimertinib was “observed irrespective of whether the patients received adjuvant chemotherapy or not. “Of patients who received adjuvant chemotherapy, 89% who received osimertinib and 49% who received placebo were alive and disease-free at 24 months (overall hazard ratio for disease recurrence or death, 0.16); of patients who not receive adjuvant chemotherapy, these percentages were 89% and 58%, respectively (overall hazard ratio, 0.23),” Wu and colleagues wrote.

The researchers explained that they are continuing to collect more mature data and to that end both investigators and patients “have continued to remain unaware of trial assignments.”

The concluded that in their “international randomized trial, adjuvant osimertinib was associated with significant improvement in disease-free survival among patients with stage IB to IIIA EGFR mutation–positive NSCLC. Osimertinib as adjuvant therapy is an effective new treatment strategy for these patients after complete tumor resection.”

Patients with resectable stage IB to III non-small-cell lung cancer who undergo adjuvant therapy with osimertinib, which targets the epidermal growth factor receptor (EGFR), were significantly more likely to be alive and disease free at 2 years than those randomized to placebo post surgery.

That finding from the 682-patient ADAURA trial was reported at the European Society for Medical Oncology (ESMO) virtual congress and simultaneously published online by The New England Journal of Medicine.

“At 24 months, 90% of the patients with stage II to IIIA disease in the osimertinib group (95% confidence interval [CI], 84-93) and 44% of those in the placebo group (95% CI, 37-51) were alive and disease-free (overall hazard ratio for disease recurrence or death, 0.17; 99.06% CI, 0.11-0.26; P<0.001),” wrote Yi-Long Wu, MD, of the Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, and Guangdong Academy of Medical Sciences, in Guangzhou, China, and colleagues.

Looking at the entire ADAURA population—stages IB to IIIA—89% of the patients in the osimertinib group (95% CI, 85 to 92) and 52% of those in the placebo group (95% CI, 46 to 58) were alive and disease-free at 24 months (overall hazard ratio for disease recurrence or death, 0.20; 99.12% CI, 0.14 to 0.30; P<0.001). At 24 months, 98% of the patients in the osimertinib group (95% CI, 95 to 99) and 85% of those in the placebo group (95% CI, 80 to 89) were alive and did not have central nervous system disease (overall hazard ratio for disease recurrence or death, 0.18; 95% CI, 0.10 to 0.33).”

At this time, overall survival data are not yet mature, but “29 patients died (9 in the osimertinib group and 20 in the placebo group).”

Wu and colleagues noted that the current standard postoperative adjuvant therapy recommendation is cisplatin-based chemotherapy, but that therapy “is associated with only a 16% decrease in the risk of disease recurrence or death at 5 years,” and just a 5% decrease in risk of death at 5 years. Moreover, the 5 year follow-up data with or without postoperative chemotherapy are disappointing: for stage IB patients the risk of disease recurrence is about 45% and that jumps to 76% for those with stage III disease.

The ADAURA researchers enrolled patients with completely resected EGFR mutation positive NSCLC from November 2015 through February 2019. They randomized 339 to osimertinib (80 mg once daily) and 343 placebo for 3 years. Prior to randomization, standard adjuvant chemotherapy was allowed. “Most patients with stage II to IIIA disease (76%) and approximately a quarter of the patients with stage IB disease (26%) received adjuvant platinum-based chemotherapy,” they wrote. Radiation therapy, pre or postoperative, was not allowed.

Among the findings:

  • At 24 months, 26 of stage II or IIIA patients in the osimertinib group (11% maturity) had disease recurrence or death.
  • At 24 months, 130 of stage II or IIIA patients in the control group (55% maturity) had disease recurrence or death.
  • Median disease-free survival was not reached (95% CI, could not be calculated to could not be calculated) in the osimertinib group.
  • Median disease-free survival was 27.5 months (95% CI, 22.0-35.0) in the placebo group.

The benefit of osimertinib was “observed irrespective of whether the patients received adjuvant chemotherapy or not. “Of patients who received adjuvant chemotherapy, 89% who received osimertinib and 49% who received placebo were alive and disease-free at 24 months (overall hazard ratio for disease recurrence or death, 0.16); of patients who not receive adjuvant chemotherapy, these percentages were 89% and 58%, respectively (overall hazard ratio, 0.23),” Wu and colleagues wrote.

The researchers explained that they are continuing to collect more mature data and to that end both investigators and patients “have continued to remain unaware of trial assignments.”

The concluded that in their “international randomized trial, adjuvant osimertinib was associated with significant improvement in disease-free survival among patients with stage IB to IIIA EGFR mutation–positive NSCLC. Osimertinib as adjuvant therapy is an effective new treatment strategy for these patients after complete tumor resection.”

  1. Be aware that this report discusses an off-label treatment of osimertinib.
  2. Note that the findings from ADAURA suggest that adjuvant chemotherapy does not affect the activity of osimertinib.

Peggy Peck, Editor-in-Chief, BreakingMED™

The ADAURA trial was funded by AstraZeneca.

Wu reported grants and personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, grants and personal fees from BMS, personal fees from Eli Lilly, personal fees from MSD, grants and personal fees from Pfizer, personal fees from Sanofi, grants and personal fees from Roche, outside the submitted work.

 

Cat ID: 24

Topic ID: 78,24,24,697,935,192,65,925,696