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ESMO 2019: Dr. Ramalingam Discusses Confirmatory Data in Advanced NSCLC

Suresh S. Ramalingam, MD
Published: Friday, Oct 18, 2019



Suresh S. Ramalingam, MD, deputy director, Winship Cancer Institute of Emory University, discusses confirmatory data in advanced non–small cell lung cancer (NSCLC) presented at the 2019 ESMO Congress.

Data from several key trials in lung cancer were presented at the 2019 ESMO Congress. Among the meeting highlights was the overall survival (OS) analysis from the phase III FLAURA trial. In the trial, treatment-naïve patients with advanced EGFR-mutant NSCLC were randomized 1:1:1 to osimertinib (Tagrisso), gefitinib (Iressa), or erlotinib (Tarceva). Notably, patients who acquired a T790M resistance mutation to gefitinib or erlotinib were allowed to crossover to osimertinib. Previously, data published in the New England Journal of Medicine demonstrated an 18.9-month median progression-free survival with osimertinib versus 10.2 months with gefitinib and erlotinib (HR, 0.46; 95% CI, 0.37-0.57; P <.0001). Updated findings showed that despite crossover, median OS was 38.6 months with osimertinib versus 31.8 months with the standard EGFR TKIs (HR, 0.799; 95% CI, 0.647-0.997; P = .0462). Based on these data, osimertinib should be the frontline standard of care for patients with EGFR-mutant NSCLC, rather than a second-line therapy wherein less patients are going to be eligible to receive it, explains Ramalingam. In order to further improve outcomes, osimertinib will be evaluated in combination in the advanced-stage disease and as adjuvant therapy, as in the phase III ADAURA trial.

Given the availability of targeted therapy, it is crucial that every patient with nonsquamous NSCLC be tested for a potentially targetable alteration, says Ramalingam. Although tissue-based assays are considered the gold standard, liquid-based assays are beginning to enter the field, due, in part, to trials like the phase II/III global BFAST trial, which confirmed the ability of blood-based next-generation sequencing to identify ALK alterations. These results serve as additional proof that plasma-based testing can be used if patients do not have enough tissue for traditional sequencing, explains Ramalingam.

Moreover, data from the phase III CheckMate-227 and IMpower110 trials demonstrated the expanding role of immunotherapy in the field. Data from the CheckMate-227 trial showed an improvement in median OS with the frontline combination of nivolumab (Opdivo) and ipilimumab (Yervoy) versus chemotherapy in patients with advanced NSCLC, irrespective of PD-L1 status (17.1 months vs. 13.9 months, respectively; HR, 0.73; 97.72% CI, 0.65-0.96; P = .007). In the IMpower110 trial, atezolizumab (Tecentriq) monotherapy was compared with platinum-based chemotherapy in previously untreated patients with advanced NSCLC who had ≥50% expression of PD-L1 on tumor cells or ≥10% expression on tumor-infiltrating immune cells. Patients who received atezolizumab alone experienced a 61% reduction in the risk of progression or death versus chemotherapy, similar to the data from the phase III KEYNOTE-042 trial with pembrolizumab (Keytruda), concludes Ramalingam.
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Suresh S. Ramalingam, MD, deputy director, Winship Cancer Institute of Emory University, discusses confirmatory data in advanced non–small cell lung cancer (NSCLC) presented at the 2019 ESMO Congress.

Data from several key trials in lung cancer were presented at the 2019 ESMO Congress. Among the meeting highlights was the overall survival (OS) analysis from the phase III FLAURA trial. In the trial, treatment-naïve patients with advanced EGFR-mutant NSCLC were randomized 1:1:1 to osimertinib (Tagrisso), gefitinib (Iressa), or erlotinib (Tarceva). Notably, patients who acquired a T790M resistance mutation to gefitinib or erlotinib were allowed to crossover to osimertinib. Previously, data published in the New England Journal of Medicine demonstrated an 18.9-month median progression-free survival with osimertinib versus 10.2 months with gefitinib and erlotinib (HR, 0.46; 95% CI, 0.37-0.57; P <.0001). Updated findings showed that despite crossover, median OS was 38.6 months with osimertinib versus 31.8 months with the standard EGFR TKIs (HR, 0.799; 95% CI, 0.647-0.997; P = .0462). Based on these data, osimertinib should be the frontline standard of care for patients with EGFR-mutant NSCLC, rather than a second-line therapy wherein less patients are going to be eligible to receive it, explains Ramalingam. In order to further improve outcomes, osimertinib will be evaluated in combination in the advanced-stage disease and as adjuvant therapy, as in the phase III ADAURA trial.

Given the availability of targeted therapy, it is crucial that every patient with nonsquamous NSCLC be tested for a potentially targetable alteration, says Ramalingam. Although tissue-based assays are considered the gold standard, liquid-based assays are beginning to enter the field, due, in part, to trials like the phase II/III global BFAST trial, which confirmed the ability of blood-based next-generation sequencing to identify ALK alterations. These results serve as additional proof that plasma-based testing can be used if patients do not have enough tissue for traditional sequencing, explains Ramalingam.

Moreover, data from the phase III CheckMate-227 and IMpower110 trials demonstrated the expanding role of immunotherapy in the field. Data from the CheckMate-227 trial showed an improvement in median OS with the frontline combination of nivolumab (Opdivo) and ipilimumab (Yervoy) versus chemotherapy in patients with advanced NSCLC, irrespective of PD-L1 status (17.1 months vs. 13.9 months, respectively; HR, 0.73; 97.72% CI, 0.65-0.96; P = .007). In the IMpower110 trial, atezolizumab (Tecentriq) monotherapy was compared with platinum-based chemotherapy in previously untreated patients with advanced NSCLC who had ≥50% expression of PD-L1 on tumor cells or ≥10% expression on tumor-infiltrating immune cells. Patients who received atezolizumab alone experienced a 61% reduction in the risk of progression or death versus chemotherapy, similar to the data from the phase III KEYNOTE-042 trial with pembrolizumab (Keytruda), concludes Ramalingam.
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