Three main clinical trials for EGFR mutation non-small cell lung carcinoma presented at ESMO Virtual Congress 2020.
FLAURA 2
The partial results of this trial that evaluated the combination of osimertinib with chemotherapy in the first line for patients with EGFR mutation were presented. The first part of FLAURA 2 assesses the safety of combining osimertinib with chemotherapy. Patients were treated with carboplatin, osimertinib and pemetrexed or with a cisplatin, osimertinib and pemetrexed regimen.
The trial has shown that the combination of osimertinib with chemotherapy is safe, with no adverse events other than those already expected with these medications. Adverse events in the group receiving the cisplatin regimen were, as expected, more frequent than in the group receiving the carboplatin regimen.
The FLAURA 2 trial will now move to the phase III randomized portion and, when completed, it will be possible to define changes or not in the current treatment pattern in the 1st line of lung cancer EGFR +.
IMpower150
This trial evaluated the combination of carboplatin, paclitaxel, bevacizumab and atezolizumab compared to a carboplatin, paclitaxel, bevacizumab regimen, in addition to a third arm with carboplatin, paclitazel and atezolizumab in patients with EGFR mutation.
IMpower150 led to the approval of the first-line four-drug regimen in untreated patients. An interesting point of the study is that it included patients with an EGFR mutation, something unusual in first-line chemotherapy trials. However, a condition for the participation of these mutated patients in EGFR is that they needed to have exhausted their treatment options with tyrosine kinase inhibitors.
Of the 78 patients with EGFR mutations, 58 had classic sensitivity mutations. And of those 58, 50 patients had received previous treatment with tyrosine kinase inhibitors
Data from subgroups of patients in this trial showed that the hazard ratio (HR) varied depending on the patient’s profile. In patients with EGFR sensitivity mutations, the HR was 0.91 with the four-drug regimen. Patients with EGFR sensitivity mutation had an HR of 0.6. And patients with
both mutations and previous treatment had an HR of 0.74. The improvement in overall survival was not seen in the group that excluded the antiangiogenic bevacizumab from the regimen.
CHRYSALIS
CHRYSALIS brings a new strategy by combining lazertinib (3rd generation EGFR inhibitor) with amivantamab (an anti-EGFR and anti-MET monoclonal antibody). The trial treated 90 patients, 25% of whom had never received previous treatment and 60% had received 3rd generation TKI.
In this phase I trial, no unexpected toxicities were observed. Only 11% of patients had grade 3 toxicity. Preliminary efficacy data shows a response rate of 36% in patients who received osimertinib previously. In patients without prior treatment, the response rate was 100% and are followed up for another 7 months.
References:
Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med. 2018;378(24):2288-2301. doi:10.1056/NEJMoa1716948
Park, K. Et. Al. Amivantamab (JNJ-61186372), a EGFR-MET bispecific antibody, in combination with Lazertinib, a 3-rd generation TKI in advanced EGFR NSCLC. ESMO virtual congress sep. 2020
Planchard, et. Al. Osimertinib plus platinum-pemetrexed in newly-diagnosed EGFR mutation (EGFRm)-positive advanced NSCLC: safety run-in results from the FLAURA2 study. ESMO virtual congress sep. 2020
Reck, M. IMpower150: Updated Efficacy Analysis in Patients With EGFR Mutations. ESMO virtual congress sep. 2020