Dr Ramalingam on Osimertinib Post-Chemoradiotherapy in Unresectable EGFR-Mutated NSCLC

Suresh S. Ramalingam, MD, FACP, FASCO, professor, Department of Hematology and Medical Oncology, Roberto C. Goizueta Distinguished Chair for Cancer Research, Emory University School of Medicine, executive director, Winship Cancer Institute of Emory University, associate vice president, cancer, Woodruff Health Sciences Center, discusses primary findings from the phase 3 LAURA trial (NCT03521154) investigating the use of osimertinib (Tagrisso) after definitive chemoradiotherapy in patients with unresectable stage III 

-mutated non–small cell lung cancer (NSCLC).

Ramalingam begins by noting that investigators enrolled patients with locally advanced NSCLC whose disease harbored 

 exon 19 deletions or L858R mutations. All patients received definitive chemoradiotherapy before being randomly assigned to osimertinib or placebo, and they were required to have a response or stable disease following chemoradiotherapy, he explains.

 demonstrated that patients treated with osimertinib (n = 143) achieved a median PFS of 39.1 months (95% CI, 31.5–not calculable) vs 5.6 months (95% CI, 3.7-7.4) for patients who received placebo (n = 73; HR, 0.16; 95% CI, 0.10-0.24; 

The 12- and 24-month PFS rates in the osimertinib arm were 74% and 65%, respectively, as opposed to respective rates of 22% and 13% in the placebo arm.

In terms of safety, Ramalingam explains that the results for osimertinib after chemoradiotherapy aligned with the established safety profile of the EGFR inhibitor, chemotherapy, and radiation, and most toxicities were manageable. He highlights that most adverse effects (AEs) were grade 1 or 2 and did not result in treatment discontinuation.

The most common any-grade AEs reported in at least 10% of patients included radiation pneumonitis (osimertinib, 48%; placebo, 38%), diarrhea (36%; 14%), rash (24%; 14%), COVID-19 (20%; 8%), paronychia (17%; 1%), cough (16%; 10%), decreased appetite (15%; 5%), dry skin (13%; 5%), pruritus (13%; 7%), stomatitis (12%; 3%), decreased white blood cell count (12%; 3%), pneumonia (11%; 8%), anemia (10%; 4%), and musculoskeletal chest pain (3%; 12%).

Videos

Suresh S. Ramalingam, MD, FACP, FASCO, discusses findings with osimertinib after definitive chemoradiotherapy in unresectable EGFR-mutated NSCLC.

Dr Ramalingam on Osimertinib Post-Chemoradiotherapy in Unresectable, Stage III, EGFR-Mutated NSCLC

Suresh S. Ramalingam, MD, FASCO, deputy director, director, Lung Cancer Program, Winship Cancer Institute of Emory University, professor, assistant dean, Roberto C. Goizueta Distinguished Chair for Cancer Research, director, Division of Medical Oncology, Department of Hematology and Medical Oncology, Emory University School of Medicine, discusses updated data with mobocertinib in 

 exon 20 insertion–positive advanced non–small cell lung cancer (NSCLC).

A phase 1/2 trial (NCT02716116) evaluated mobocertinib in patients with 

 exon 20 insertion–mutated metastatic NSCLC who had received at least 1 prior line of therapy for locally advanced or metastatic disease. Patients received mobocertinib at a dose of 160 mg once daily. 

The updated data, which were presented during the 2021 ASCO Annual Meeting, indicated an objective response rate of 28% and a median duration of response of 17.5 months in platinum-pretreated patients. These results indicate that mobocertinib could represent an effective agent for patients with 

 exon 20 insertion mutations, says Ramalingam. Moreover, the median progression-free survival in this cohort was 7.3 months, and the median overall survival was 24 months.

For a group of patients for whom there hasn’t been an effective targeted therapy until recently with the approval of amivantamab-vmjw (Rybrevant), these data are clinically meaningful, concludes Ramalingam.

Suresh S. Ramalingam, MD, FASCO, discusses updated data with mobocertinib in EGFR exon 20 insertion–positive advanced non–small cell lung cancer.

Dr. Ramalingam on Updated Data With Mobocertinib in EGFR Exon 20 Insertion+ NSCLC

Suresh S. Ramalingam, MD, FASCO, deputy director, director, Lung Cancer Program, Winship Cancer Institute of Emory University, professor, assistant dean, Roberto C. Goizueta Distinguished Chair for Cancer Research, director, Division of Medical Oncology, Department of Hematology and Medical Oncology, Emory University School of Medicine, discusses treatment after osimertinib (Tagrisso) in 

-mutant non–small cell lung cancer (NSCLC).

The current standard of care for patients with advanced 

-mutant NSCLC is chemotherapy, says Ramalingam. Previously, findings from an exploratory analysis of the phase 3 IMpower150 trial suggested that atezolizumab (Tecentriq) plus chemotherapy and bevacizumab (Avastin) could provide clinical benefit to patients with 

mutations who failed on treatment with TKIs. However, data from a single-center, retrospective study presented during the 2021 European Lung Cancer Virtual Congress demonstrated that treatment with chemotherapy plus immunotherapy did not demonstrate significant clinical benefit vs chemotherapy alone in patients with 

-mutated NSCLC after progression on osimertinib.

Results showed that the median overall survival (OS) for patients who received chemotherapy plus immunotherapy (n = 12) was 10.9 months (95% CI, 9.4–not estimable [NE]) vs 10.6 months (95% CI, 6.9-19.5) with chemotherapy alone (n = 29). In patients who were treated with chemotherapy plus bevacizumab (n = 34), the median OS was 13.9 months (95% CI, 10.2–NE).

These results confirm the activity of chemotherapy in patients who progress on osimertinib, says Ramalingam. However, whether the addition of bevacizumab and immunotherapy provide additional benefit should be verified in a prospective trial. To that end, the phase 3 KEYNOTE-789 trial is evaluating pembrolizumab (Keytruda) plus pemetrexed (Alimta) and platinum chemotherapy in patients with TKI-resistant 

Suresh S. Ramalingam, MD, FASCO, deputy director, director, Lung Cancer Program, Winship Cancer Institute of Emory University, professor, assistant dean, Roberto C. Goizueta Distinguished Chair for Cancer Research, director, Division of Medical Oncology, Department of Hematology and Medical Oncology, Emory University School of Medicine, discusses treatment after osimertinib (Tagrisso) in EGFR-mutant non–small cell lung cancer (NSCLC).

Dr. Ramalingam on Treatment After Osimertinib in EGFR-Mutant NSCLC

Suresh S. Ramalingam, MD, FASCO, deputy director of Winship Cancer Institute of Emory University, discusses the current treatment parameters for osimertinib (Tagrisso) in 

-mutant non—small cell lung cancer and ongoing research with the agent.

Patients diagnosed with lung adenocarcinoma or nonsquamous lung cancer receive molecular testing, and treatment should be held until the results are given, explains Ramalingam. For patients with 

 exon 19 or exon 21 mutations, the frontline therapy is osimertinib outside of a clinical trial.

An ECOG trial examining osimertinib plus bevacizumab (Avastin) versus osimertinib alone will soon launch and give insight on combining another targeted agent with the best-in-class TKI inhibitor, says Ramalingam. Research is also looking into understanding the mechanisms of resistance to osimertinib and developing novel approaches to delay or overcome resistance, concludes Ramalingam.

View more from the 2020 Winter Lung Cancer Conference

Suresh S. Ramalingam, MD, FASCO, discusses the current treatment parameters for osimertinib in EGFR-mutant non–small cell lung cancer and ongoing research with the agent.

Dr. Ramalingam on Treatment Parameters for Osimertinib in Lung Cancer

Suresh S. Ramalingam, MD, FASCO, deputy director of Winship Cancer Institute of Emory University, discusses updated data from the FLAURA trial in 

-mutant non—small cell lung cancer (NSCLC).

Updated data of the FLAURA study presented at the 2019 ESMO Congress showed that the median overall survival of patients treated with osimertinib (Tagrisso) was superior at 38.6 months versus 31.8 months in the control arm. Additionally, the safety profile was shown to be tolerable despite a longer duration of exposure compared with first- or second-generation TKIs.

In a crossover report, 70% of patients received a subsequent therapy. In the control group, which comprised erlotinib (Tarceva) or gefitinib (Iressa) in the first-line setting, and received second-line therapy, 47% of patients received osimertinib, which aligned with what is seen with T790M, which is approximately 50% in the aquired resistance setting for erlotinib or gefitinib. Despite the crossover being offered in the second-line setting in a higher number of patients, osimertinib improved OS. Ramalingam believes these results negate arguments for regarding sequencing osimertinib in second-line or beyond. The results of the FLAURA study shows osimertinib has emerged as the preferred frontline TKI for 

View more from the 2019 New York Lung Cancers Symposium

Suresh S. Ramalingam, MD, FASCO, discusses updated data from the FLAURA trial in EGFR-mutant non–small cell lung cancer.

Suresh S. Ramalingam, MD, FASCO

Articles

Dr Ramalingam on Osimertinib Post-Chemoradiotherapy in Unresectable, Stage III, EGFR-Mutated NSCLC

Dr. Ramalingam on Updated Data With Mobocertinib in EGFR Exon 20 Insertion+ NSCLC

Dr. Ramalingam on Treatment After Osimertinib in EGFR-Mutant NSCLC

Dr. Ramalingam on Treatment Parameters for Osimertinib in Lung Cancer

Dr. Ramalingam on FLAURA Trial Results in EGFR-Mutant NSCLC