Patients with resectable non-small cell lung cancer (NSCLC) often develop (fatal) distant recurrences after surgery. Recently, the ADAURA trial showed a significant improvement in disease-free survival (DFS) in patients with resectable, EGFR-mutated NSCLC who were treated with the tyrosine kinase inhibitor osimertinib. More detailed analysis of ADAURA now shows osimertinib significantly decreases development of brain metastases.

Approximately 30% of patients with NSCLC present with resectable disease at the time of diagnosis. Surgery with curative intent is the primary treatment for these patients. In addition, adjuvant cisplatin-based chemotherapy is recommended for patients with resected stage II-IIIA NSCLC and selected patients with stage IB disease to decrease the risk of recurrence [1]. However, rates of disease recurrence after surgery and adjuvant chemotherapy remain high across disease stages and postoperative chemotherapy used. Distant recurrence, like CNS recurrence, are associated with poor prognosis. Recently, a first analysis of the phase 3 ADAURA trial demonstrated a highly significant and clinically meaningful improvement in DFS in patients with EGFR-mutated, resectable NSCLC (stage IB/II/IIIA) who were treated with adjuvant osimertinib (80 mg/day) until recurrence or for a maximum of 3 years [2]. At ESMO 2020, Dr Masahiro Tsuboi (National Cancer Center Hospital East, Japan) presented updated results from ADAURA [3].

Median DFS in patients (stage IB/II/IIIA) treated with osimertinib (n=339) was not yet reached versus 27.5 months in patients treated with placebo (n=343; HR 0.20; P<0.0001). In patients with stage II/IIIA, median DFS was not reached for patients treated with osimertinib (n=233) and 19.6 months for patients treated with placebo (n=237; HR 0.17; P<0.0001). In the osimertinib arm, 11% had an event (disease recurrence or death) at the time of cut-off versus 46% of patients in the placebo arm. In the osimertinib arm, recurrences were mostly local or regional (62%), whereas in the placebo arm the majority of recurrences were distant (61%). Of all patients treated with osimertinib, 1% developed an CNS recurrence versus 10% of all patients treated with placebo. In line with this, median CNS DFS was not yet reached in the osimertinib arm versus 48.2 months in the placebo arm (HR 0.18; P<0.0001). In other words, the estimated probability of observing CNS recurrence (or death) after 18 months was <1% with osimertinib and 9% with placebo.

Based on these results, Prof. Tsuboi concluded that adjuvant treatment with osimertinib in patients with resected, EGRF-mutated NSCLC (stage IB-IIIA) is a highly effective practice to reduce the risk of CNS recurrence. Commenting on the presentation, Prof. Johan Vansteenkiste (University Hospital Leuven, Belgium) cautioned that impressive DFS data eventually have to be translated into better cure rates (i.e. significant improvement in overall survival). So, we have to wait for mature OS data. In addition, Prof. Vansteenkiste remarked, a substantial proportion of NSCLC patients stage IA-IIIA is cured after surgery. Therefore, to minimise overtreatment, parameters have to be developed to select the right patients for adjuvant osimertinib.

 

  1. Postmus PE, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017;28 (Suppl 4):iv1–iv21.
  2. Herbst RS, et al. Osimertinib as adjuvant therapy in patients (pts) with stage IB–IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. ASCO 2020, abstract LBA5.
  3. Tsuboi M, et al. Osimertinib adjuvant therapy in patients (pts) with resected EGFR mutated (EGFRm) NSCLC (ADAURA): Central nervous system (CNS) disease recurrence. ESMO 2020 Virtual, abstract LBA1.