Advertisement


Rami Manochakian, MD, on NSCLC: Commentary on the ADAURA Trial of Osimertinib

2023 ASCO Annual Meeting

Advertisement

Rami Manochakian, MD, of Mayo Clinic Florida, offers his perspective on the new phase III findings on osimertinib, a third-generation, central nervous system EGFR tyrosine kinase inhibitor, which demonstrated an unprecedented overall survival benefit for patients with EGFR-mutated, stage IB–IIIA non–small cell lung cancer (NSCLC) after complete tumor resection, with or without adjuvant chemotherapy (Abstract LBA3).



Transcript

Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Rami Manochakian: The ADAURA Trial is a randomized, double-blind, phase three trial that enrolled hundreds of patients with early stage, non-small cell lung cancer with EGFR mutation. In particular, patient with stage 1B to 3A who underwent resection. The trial randomized the patient to either osimertinib, which is a third generation tyrosine kinase inhibitor, anti-EGFR, or placebo for three years. A few years ago, the primary endpoint of the trial was presented, which was the disease-free survival. And the study has shown significant improvement in disease-free survival, which led to the drug being approved and currently used in the United States and many other parts of the words. In this ASCO Annual Meeting, the study investigators presented the overall survival data at the plenary session. This study has shown exciting overall survival benefit for patient with stage 2 to 3A. The five-year survival was 85% for the patient who received osimertinib versus 73% for patient who received placebo. The median survival was not met yet. For patient with stage 1B to 3A, the hazard ratio was also 0.49 with a median survival also not reached. And the five-year survival was 88% versus 78%. Why is this study important? This study has shown significant improvement in overall survival. This hazard ratio mean that there is a decrease by 51% chance of death. This overall survival data means that osimertinib increase the chance of a cure. This is exciting. This is so important for our patients. This concept of personalized medicine, targeted therapy for patient with early stage non-small cell lung cancer, who has this EGFR mutation, being on this drug, helping them live longer, helping them potentially being cured. I do want to acknowledge few points that has been brought up by many specialists and oncologists about this trial. While we're very excited, beyond thrilled, about the overall survival benefit, we need to acknowledge that, just like any other cancer drug, there is some toxicity involved. While we can say that the toxicity profiles for this drug, in this trial, as many like to use the words, was acceptable or manageable. That may not be the case for every patient. Some patient may not tolerate the drug very well, and we owe it to our patients to discuss what to expect as far as side effects. And while they're on this drug, manage these side effects and address them properly. The other point also I'd like to bring up, which was brought up by many, is that in the placebo arm, there are some patients when their disease recurred, did not get osimertinib for a lot of different reasons. While I don't think this would affect the impressive positive results of this study, but it's definitely something to keep reminding us about the importance of access. And osimertinib is a standard of care drug, whether in the stage four setting and now in the early stage after resection, and every patient anywhere and everywhere should have access to it. Another important point we need to address is, do these patients need to be on osimertinib for three years? We don't know. Maybe some patient could benefit by being on it for a shorter period of time and some may need it for that long. I think we need study to look into that. And kudos to the investigators of this trial, They are looking as at tools such as free cDNA to see if some patients may benefit from being on it for longer or shorter period of time. And last but not least, I think we need to always remember that only patients who we know their cancer harbors EGFR mutation can get this drug, which remind us of the importance of testing every patient with early stage non-small cell lung cancer for EGFR mutation to know if they have it so they can get on this drug.

Related Videos

Prostate Cancer

Alicia K. Morgans, MD, MPH, and Karim Fizazi, MD, on Prostate Cancer: Phase III Results on Talazoparib Plus Enzalutamide as First-Line Treatment

Alicia K. Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Karim Fizazi, MD, of Institut Gustave Roussy, University of Paris-Saclay, discuss findings from the TALAPRO-2 study, which showed that talazoparib plus enzalutamide improved radiographic progression–free survival over standard-of-care enzalutamide as first-line treatment for patients with metastatic castration-resistant prostate cancer and HRR gene alterations. This regimen also delayed the time to deterioration in global health status and quality of life (Abstract 5004).

Myelodysplastic Syndromes

Amer Methqal Zeidan, MBBS, MHS, on Myelodysplastic Syndromes: New Data From the IMerge Study of Imetelstat

Amer Methqal Zeidan, MBBS, MHS, of Yale University and Yale Cancer Center, discusses phase III findings on the first-in-class telomerase inhibitor imetelstat, which was given to patients with heavily transfusion-dependent non-del(5q) lower-risk myelodysplastic syndromes that are resistant to erythropoiesis-stimulating agents. Imetelstat resulted in a significant and sustained red blood cell (RBC) transfusion independence in 40% of these heavily transfused patients. The response was also durable and accompanied by an impressive median hemoglobin rise of 3.6 g/dL, and seen in patients with and without ring sideroblasts. Importantly, reduced variant allele frequency was observed in the most commonly mutated myeloid genes which correlated with duration of transfusion independence and hemoglobin rise, therefore suggesting a disease-modifying potential of this agent (Abstract 7004).

Lung Cancer

Narjust Florez, MD, and Ticiana Leal, MD, on Metastatic NSCLC: Tumor Treating Fields Therapy After Platinum Resistance

Narjust Florez, MD, of Dana-Farber Cancer Institute, and Ticiana Leal, MD, of Winship Cancer Institute of Emory University, discuss the use of tumor treating fields therapy, in which electric fields disrupt processes critical for cancer cell viability. Already approved by the FDA to treat glioblastoma and mesothelioma, the treatment has extended overall survival in this phase III study of patients with metastatic non–small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy, without exacerbating systemic toxicities (Abstract LBA9005).

Issues in Oncology

Carmen E. Guerra, MD, MSCE, on Diversity, Equity, and Inclusion in Clinical Trials: Expert Commentary

Carmen E. Guerra, MD, MSCE, of the University of Pennsylvania Abramson Cancer Center, discusses three key abstracts presented at ASCO: strategies to increase accrual of underrepresented populations in Alliance NCTN trials, how patient-clinician education can strengthen partnerships and improve diversity in breast and lung cancer trials, and mediators of racial and ethnic inequities in clinical trial participation among U.S. patients with cancer from 2011 to 2022 (Abstracts 6509, 6510, 6511).

Bladder Cancer
Immunotherapy

Shilpa Gupta, MD, on Urothelial Carcinoma: Long-Term Outcome of Enfortumab Vedotin Plus Pembrolizumab

Shilpa Gupta, MD, of Cleveland Clinic, discusses the results from the EV-103 study and the unmet need for effective first-line therapies in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma. After nearly 4 years of follow-up, the trial findings showed that enfortumab vedotin-ejfv plus pembrolizumab continues to demonstrate promising survival trends with rapid and durable responses in this population (Abstract 4505).

Advertisement

Advertisement




Advertisement