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This is Part 3 of EGFR-Mutant NSCLC: Treatment Considerations for Early-Stage Disease, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Stephen Liu, Tina Cascone, and Susan Scott discuss the treatment of unresectable EGFR-mutant non–small cell lung cancer (NSCLC). The patient is a 66-year-old woman with a right upper lobe lung mass found on a screening CT scan. She has a 37-year history of smoking and quit 6 years ago. PET scan showed a hypermetabolic right upper lobe mass and mediastinal adenopathy. Bronchoscopy confirms adenocarcinoma in the right upper lobe and contralateral mediastinal adenopathy in R4, R7, and L4. With biopsy-confirmed N3 adenopathy, the multidisciplinary team determines she has unresectable stage III NSCLC. In the conversation that follows, the faculty discuss the importance of obtaining molecular testing to ensure optimal management of unresectable NSCLC, the use of concurrent chemoradiation, the role of osimertinib consolidation therapy for patients with EGFR-mutant NSCLC, and their approach to surveillance.
This is Part 2 of EGFR-Mutant NSCLC: Treatment Considerations for Early-Stage Disease, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Stephen Liu, Tina Cascone, and Susan Scott discuss the treatment of resectable EGFR-mutant non–small cell lung cancer (NSCLC). The patient is a 70-year-old man who presented with a persistent cough. Chest x-ray showed a right upper lobe ground glass infiltrate, and symptoms persisted following treatment with antibiotics. A CT scan revealed a suspicious right upper lobe lung nodule, which was hypermetabolic on PET scan with mild uptake in a right paratracheal lymph node. Bronchoscopy and endobronchial ultrasound revealed lung adenocarcinoma in the right upper node and R4 lymph node. He was offered neoadjuvant cisplatin plus pemetrexed plus pembrolizumab, but is seeking another opinion. In the conversation that follows, the faculty discuss the importance of molecular testing prior to initiating treatment with immunotherapy, how to navigate situations where repeat biopsy is necessary, the role of adjuvant osimertinib following resection for EGFR-mutant NSCLC, and more.
This is Part 2 of Clinical Perspectives on KRAS-Mutant NSCLC, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Gregory Riely, Rebecca Heist, and Joshua Sabari discuss the second-line treatment of a patient with KRAS-mutant metastatic non–small cell lung cancer (NSCLC). The patient is a 67-year-old woman who is diagnosed with lung adenocarcinoma with oligoprogressive disease, PD-L1 expression of 10%, and KRAS G12C, STK11, and KEAP1 mutations. She receives initial therapy with chemotherapy and dual checkpoint inhibition but shows evidence of disease progression after 8 cycles of therapy. In the conversation that follows, the faculty discuss the local treatment options for oligoprogressive KRAS G12C–mutant lung cancer after disease progression, how the currently approved KRAS G12C inhibitors compare with docetaxel, and treatment considerations when using KRAS inhibitors.
This is Part 1 of Clinical Perspectives on KRAS-Mutant NSCLC, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Gregory Riely, Rebecca Heist, and Joshua Sabari discuss the first-line treatment of a patient with KRAS-mutant non–small cell lung cancer (NSCLC). The patient is a 58-year-old woman who presents with bilateral lung masses and is found to have diffusely metastatic lung adenocarcinoma with KRAS G12D, TP53, and STK11 mutations, and a PD-L1 expression of 30%. In the conversation that follows, the faculty discuss the importance of upfront testing for all genomic alterations, whether all KRAS mutations are actionable, and the role of tumor histology and PD-L1 status in determining appropriate first-line therapy.
This is Part 3 of First-Line Immunotherapy for Metastatic NSCLC: Special Populations and Unmet Needs, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Roy Herbst, Charu Aggarwal, and Karen Reckamp discuss the first-line management of a patient with metastatic non–small cell lung cancer (NSCLC) and brain metastasis. The patient is a 64-year-old male who presents with left neck adenopathy. He is a former smoker with a 15 pack-year smoking history but quit 10 years ago. Positron-emission tomography shows an FDG-avid large left upper lobe mass with left axillary, left cervical, and left mediastinal lymph nodes, as well as a left lower lobe satellite lesion. Fine-needle aspiration of the left cervical lymph node is positive for NSCLC, adenocarcinoma subtype. PD-L1 TPS is 1%. Next-generation sequencing reveals no actionable mutations. During staging workup and molecular profiling, he develops weakness on his left side, and brain MRI reveals a 1.6-cm right frontal lobe mass with surrounding edema. In the conversation that follows, the faculty discuss whether surgical resection would be appropriate for this patient with brain metastasis, the optimal systemic treatment regimen of choice following local treatment of the brain lesion, and whether restaging is necessary.
This is Part 2 of First-Line Immunotherapy for Metastatic NSCLC: Special Populations and Unmet Needs, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Roy Herbst, Charu Aggarwal, and Karen Reckamp discuss the first-line management of a patient with PD-L1–negative metastatic non–small cell lung cancer (NSCLC). The patient is a 57-year-old Asian American female who presents with stage IV lung adenocarcinoma with a left lower lobe mass, bulky hilar and mediastinal metastases, and multiple bone lesions, including in the ribs and pelvis. She is a former smoker with a 15 pack-year smoking history but quit 20 years ago. Her performance status is 1. Fine-needle aspiration of the left lower primary is positive for lung adenocarcinoma; her PD-L1 expression is 0%, and next-generation sequencing reveals no actionable markers. In the conversation that follows, the faculty discuss potential treatment options in the first-line setting, whether a poor performance status or other risk factors would change a decision to use dual checkpoint blockade, and the importance of obtaining an accurate molecular profile, particularly in patients with lung cancer who have a history of smoking.
This is Part 1 of First-Line Immunotherapy for Metastatic NSCLC: Special Populations and Unmet Needs, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Roy Herbst, Charu Aggarwal, and Karen Reckamp discuss the first-line management of a patient with metastatic non–small cell lung cancer (NSCLC) with squamous cell histology. The patient is a 63-year-old man with a prior 30 pack-year smoking history who presents with cough and shortness of breath. A CT scan reveals a left upper lobe primary mass, mediastinal and hilar adenopathy, and bilateral lung and bone metastases. Fine-needle biopsy reveals TTF1-negative NSCLC with squamous cell histology. Brain MRI is negative for metastatic disease, and PD-L1 expression is 10%. In the conversation that follows, the faculty discuss next steps for this patient, whether tumor profiling is necessary in patients with squamous histology, considerations for the use of CTLA-4 inhibitors, and what immune-related adverse events clinicians should be aware of in patients with lung cancer.
This is Part 3 of ALK-Positive Metastatic NSCLC: Where Are We Now?, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Todd Bauer, Narjust Florez, and Sai-Hong Ignatius Ou discuss the second-line treatment of ALK-positive non–small cell lung cancer (NSCLC) with CNS progression on first-line crizotinib. The patient was initially diagnosed with metastatic EML4::ALK-positive NSCLC at age 40 years in 2013. He did not have any CNS lesions present at the time of diagnosis and started treatment with first-line crizotinib. In February 2014, he developed seizures and was found to have multiple CNS lesions, which were treated with whole-brain irradiation. He subsequently enrolled in the phase I lorlatinib trial in April 2014. In November 2018, while at the 75-mg daily dose, he developed grand mal seizures with no evidence of disease progression, and lorlatinib was held; 11 days later, he returned to his baseline. He resumed treatment with lorlatinib at 50 mg daily and has maintained a near–complete response since that time. In April 2024, he developed recurrent seizures and has been holding lorlatinib since that time with resolution of symptoms. In the conversation that follows, the faculty discuss the long-term toxicities vs benefit of lorlatinib, the management of toxicities associated with lorlatinib, and the impact of dose reduction on efficacy.
This is Part 2 of ALK-Positive Metastatic NSCLC: Where Are We Now?, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Todd Bauer, Narjust Florez, and Sai-Hong Ignatius Ou discuss the first-line management of ALK-positive non–small cell lung cancer (NSCLC) with CNS metastases at basement and CNS toxicity early in treatment. The patient is a 76-year-old prior smoker who presented to the emergency room in February 2024 with complaints of dyspnea. Imaging revealed a 3.2-cm right lower lobe lung mass and a widely metastatic process. Lung biopsy confirmed metastatic NSCLC, and liquid next-generation sequencing (NGS) revealed an EML::ALK variant 3a/b rearrangement. MRI of the brain revealed a 4-mm right frontal lobe metastasis. The patient started first-line lorlatinib at 100 mg daily in March 2024, and 3.5 weeks later showed decreased conspicuity of the CNS lesion. However, he also began to note mild confusion and “chemo fog” after his second cycle of therapy. In the conversation that follows, the faculty discuss common toxicities associated with lorlatinib, the role of dose reduction in managing toxicities, and the importance of taking a social history to obtain a holistic understanding of patients.
This is Part 1 of ALK-Positive Metastatic NSCLC: Where Are We Now?, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Todd Bauer, Narjust Florez, and Sai-Hong Ignatius Ou discuss the first-line management of metastatic non–small cell lung cancer (NSCLC) with CNS metastases at baseline. The patient presented at age 38 years for evaluation of headaches in 2021. A head CT revealed two lesions with surrounding edema but no midline shift, which was concerning for metastatic disease. A CT of the chest, abdomen, and pelvis revealed a 4-cm left upper lobe lung mass, hilar adenopathy, and a 2-cm liver lesion. Liver biopsy confirmed metastatic NSCLC. While awaiting next-generation sequencing (NGS), the patient was started on carboplatin plus pemetrexed and was referred for radiation to the CNS lesions. NGS returned with an EML4::ALK variant 1 translocation, and she began treatment with alectinib. One week after alectinib was started, she underwent stereotactic radiosurgery to the CNS lesion. In the conversation that follows, the faculty discuss the importance of NGS testing for actionable driver mutations regardless of smoking history, appropriate therapy options when starting treatment prior to having NGS results, and the role of stereotactic radiosurgery in the first-line setting.
Narjust Florez, MD, of the Dana-Farber Cancer Institute, and Suresh S. Ramalingam, MD, of Emory University School of Medicine, Winship Cancer Institute, discuss potentially practice-changing phase III results from the LAURA study. This trial showed that osimertinib after definitive chemoradiation therapy improved progression-free survival for patients with unresectable stage III EGFR-mutated non–small cell lung cancer (NSCLC), suggesting this agent may represent a new standard of care in this setting (LBA4).
Minesh P. Mehta, MD, of Miami Cancer Institute, part of Baptist Health South Florida, discusses results from the METIS (EF-25) trial evaluating the efficacy and safety of tumor treating fields therapy following stereotactic radiosurgery in patients with mutation-negative non–small cell lung cancer (NSCLC) and brain metastases. Tumor treating fields therapy prolongs time to intracranial disease progression and may postpone whole-brain radiation therapy without declines in quality of life and cognition (Abstract 2008).
Narjust Florez, MD, of Dana-Farber Cancer Institute, and David R. Spigel, MD, of Sarah Cannon Research Institute, discuss phase III findings showing that durvalumab as consolidation treatment after concurrent platinum-based chemoradiotherapy improved survival outcomes compared with placebo in patients with limited-stage small cell lung cancer. According to Dr. Spigel, these data support durvalumab as a new standard of care in this population (Abstract LBA5).
Tony S.K. Mok, MD, of The Chinese University of Hong Kong, discusses phase III findings from the KRYSTAL-12 study, which showed that adagrasib improved progression-free survival and overall response rate over docetaxel in patients with locally advanced or metastatic non–small cell lung cancer harboring a KRAS G12C mutation who had previously received a platinum-based chemotherapy with anti–PD-(L)1 treatment.
Heather Wakelee, MD, of Stanford University Medical Center, discusses phase III findings showing that the disease-free survival benefit with adjuvant atezolizumab continues to translate into a positive overall survival trend vs best supportive care in patients with stage II–IIIA non–small cell lung cancer (NSCLC). These results further support the use of adjuvant atezolizumab in PD-L1–selected populations, according to Dr. Wakelee (LBA8035).
Tomasz Jankowski, MD, PhD, of Poland’s Medical University in Lublin, discusses a phase II study of THIO, a telomere-targeting agent followed by cemiplimab-rwlc for a difficult-to-treat population of patients with advanced non–small cell lung cancer (Abstract 8601).
Pasi A. Jänne, MD, PhD, of Dana-Farber Cancer Institute, discusses an exploratory analysis from the FLAURA2 study, which indicates that baseline levels of plasma EGFR mutation may be prognostic and predictive of clinical benefit with osimertinib plus chemotherapy vs osimertinib alone for patients with non–small cell lung cancer (NSCLC).
Akhil G. Pachimatla, MD, of Roswell Park Comprehensive Cancer Center, discusses study findings showing that, in patients with non–small cell lung cancer (NSCLC), image-based adiposity measures show stronger correlations with gene-expression changes in these tumors than body mass index measures. Dr. Pachimatla explains the clinical implications (Abstract 37).
This is Part 3 of Optimizing Outcomes for Patients With Locally Advanced and Metastatic NSCLC, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Melissa Johnson, Vamsidhar Velcheti, and Helena Yu discuss the neoadjuvant treatment of patients with EGFR-positive lung adenocarcinoma. The patient is a 75-year-old female with a minimal smoking history who was admitted to the hospital for an electrolyte abnormality. Scans show a right upper lobe spiculated mass with right hilar lymphadenopathy, and biopsies confirm a diagnosis of primary lung adenocarcinoma, with a 4R lymph node testing positive as well. Next-generation sequencing is performed showing PALB2, PD-L1 negative, EGFR L861Q, and a low tumor mutation burden. The faculty discuss next steps for this patient, the optimal neoadjuvant therapy for patients with uncommon EGFR mutations, and whether osimertinib would be appropriate as a treatment option.
This is Part 2 of Optimizing Outcomes for Patients With Locally Advanced and Metastatic NSCLC, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Melissa Johnson, Vamsidhar Velcheti, and Helena Yu discuss the management of stage IIIA non–small cell lung cancer (NSCLC) in a former smoker. The patient is a 62-year-old female, a former smoker with a 25 pack-year history, who presents with shortness of breath and cough. Chest CT shows a large right upper lobe mass and an enlarged pretracheal lymph node, both of which are FDG-avid on PET scan. The case goes to multidisciplinary review, and he is ultimately diagnosed with a T4N0 squamous cancer. The faculty discuss the multidisciplinary management for a patient such as this, the possibility of complete resection, and the role of neoadjuvant immunotherapy plus chemotherapy for stage III NSCLC.
This is Part 1 of Optimizing Outcomes for Patients With Locally Advanced and Metastatic NSCLC, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Melissa Johnson, Vamsidhar Velcheti, and Helena Yu discuss the management of locally advanced non–small cell lung cancer (NSCLC). The patient is a 62-year-old male former smoker with a 45-pack-year history. He has multiple comorbidities and presents with shortness of breath and cough. PET/CT scans show hypermetabolism in a subcarinal node and right lower lobe pulmonary nodule, and right perihilar thickening. Bronchoscopy reveals squamous T2aN2 NSCLC. Next-generation sequencing is performed, showing a PD-L1 expression of 15%; high tumor mutation burden; KIT, FGFR1, PIK3CA and PIK3CA amplification; and the tumor is microsatellite stable. The faculty discuss how the treatment landscape for locally advanced NSCLC has changed since the approval of nivolumab plus chemotherapy, how to manage dose delays in the neoadjuvant setting, and whether additional adjuvant therapy is appropriate in patients who achieve complete response to neoadjuvant chemotherapy plus immunotherapy.
This is Part 3 of New Directions in Nonmetastatic Non–Small Cell Lung Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Heather Wakelee, Tina Cascone, and Marina Garassino discuss the management of EGFR-mutated early-stage non–small cell lung cancer (NSCLC). The patient is a 48-year-old woman who is being evaluated for a 3-cm mass in the right lower lobe that was detected on chest x-ray after a car accident. Biopsy confirms adenocarcinoma, and PD-L1 expression is 85%. Her brain MRI is negative. At multidisciplinary tumor board, there is a discussion of whether to start chemotherapy plus immune checkpoint inhibitor therapy immediately vs going straight to surgery given the limited extent of disease. The faculty discuss the importance of testing molecular testing for EGFR and ALK mutations prior to the start of immune checkpoint inhibitor therapy, whether adjuvant osimertinib should be continued for more than 3 years, and the clinical implications of the ADAURA and ALINA trials.
This is Part 2 of New Directions in Nonmetastatic Non–Small Cell Lung Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Heather Wakelee, Tina Cascone, and Marina Garassino discuss the management of PD-L1–negative early-stage non–small cell lung cancer (NSCLC). The patient is a 75-year-old man who presented to his primary care provider for evaluation of worsening cough and hemoptysis. He was a smoker for 45 years, has an ECOG performance score of 1, has hypertension and COPD, and is relatively active. Chest x-ray reveals a large left lung mass, which biopsy confirms as squamous cell carcinoma. PET and brain MRI are negative, but there is a 4.3-cm lower lobe mass and a level 4L lymph node; endobronchial ultrasound does not confirm disease in any station. The final staging was stage IIA T2bN0. At a multidisciplinary tumor board, the lesion was determined to be resectable. His PD-L1 level is 0%. In the conversation that follows, the faculty discuss how treatment for early-stage lung cancer differs based on PD-L1 expression; the multidisciplinary management of immune-related adverse events; and perioperative approaches to immunotherapy.
This is Part 1 of New Directions in Nonmetastatic Non–Small Cell Lung Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Heather Wakelee, Tina Cascone, and Marina Garassino discuss immune checkpoint inhibitor strategies for resectable nonmetastatic non–small cell lung cancer (NSCLC). The patient is an active 68-year-old woman with a 70-pack-year smoking history. On screening computed tomography, she was found to have a 3.7-cm right upper lobe mass, which biopsy confirmed as adenocarcinoma. Further staging revealed uptake in a 10R node on positron-emission tomography, but no other suspicious sites. In the conversation that follows, the faculty discuss the importance of completing staging prior to resection; how PD-L1 testing informs therapeutic strategies; and the role of neoadjuvant, perioperative, and adjuvant immune checkpoint inhibitor therapy in treating stage II/III NSCLC.
Jarushka Naidoo, MHS, MBBCh, of the Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, discusses some of the key lung cancer data presented at the ESMO Congress 2023: CheckMate 77T, a phase III study of nivolumab, chemotherapy, and surgery for previously untreated resectable stage II–IIIB NSCLC; the ALINA study of alectinib vs chemotherapy in patients with early-stage ALK-positive NSCLC; and overall survival data from KEYNOTE-671, which established the role of chemoimmunotherapy and pembrolizumab. Dr. Naidoo also reviews data in small cell lung and thymic cancers.
Benjamin Besse, MD, PhD, of the Gustave Roussy Cancer Centre, discusses new findings on AZD7789, which targets PD-1 and TIM-3, in patients with stage IIIB–IV non–small cell lung cancer (NSCLC) with previous anti–PD-L1 therapy. This bispecific antibody showed manageable safety and preliminary efficacy at tolerable doses (Abstract 1313MO).
Benjamin Besse, MD, PhD, of the Gustave Roussy Cancer Centre, discusses phase II findings from the HERTHENA-Lung01 study, which showed patients with previously treated EGFR-mutated non–small cell lung cancer may benefit from the antibody-drug conjugate patritumab deruxtecan after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (Abstract OA05.03). The phase III HERTHENA-Lung02 trial is ongoing.
Mark M. Awad, MD, PhD, of Dana-Farber Cancer Institute, discusses phase III findings from the CheckMate 816 trial, which showed a potential clinical benefit to neoadjuvant nivolumab plus ipilimumab vs chemotherapy in patients with resectable non–small cell lung cancer (NSCLC) (Abstract 1261O).
Hossein Borghaei, DO, of Fox Chase Cancer Center, discusses phase III findings from the SAPPHIRE study of sitravatinib plus nivolumab vs docetaxel in patients with previously treated, advanced nonsquamous non–small cell lung cancer (NSCLC) (Abstract LBA63).
Ze-rui Zhao, PhD, of China’s Sun Yat-sen University Cancer Center, discusses new phase II findings on stereotactic body radiation therapy (SBRT) with sequential immunochemotherapy as a neoadjuvant treatment of patients with resectable non–small cell lung cancer (NSCLC). This therapy yielded a high major pathologic response rate, according to Dr. Zhao (Abstract LBA60).
Jonathan D. Spicer, MD, PhD, of McGill University, discusses findings from the KEYNOTE-671 study of perioperative pembrolizumab for patients with resectable early-stage non–small cell lung cancer (NSCLC). Neoadjuvant pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab improved overall survival compared with neoadjuvant chemotherapy and resection alone in stage II, IIIA, or IIIB (N2) disease (Abstract LBA56).
Tina Cascone, MD, PhD, of The University of Texas MD Anderson Cancer Center, discusses new phase III findings from the CheckMate 77T trial of patients with previously untreated resectable stage II–IIIB non–small cell lung cancer (NSCLC). The trial showed clinically meaningful improvement in event-free survival with neoadjuvant nivolumab plus chemotherapy followed by surgery and adjuvant nivolumab vs chemotherapy or placebo (Abstract LBA1).
Gilberto de Lima Lopes, Jr, MD, MBA, of the Sylvester Comprehensive Cancer Center at the University of Miami, comments on four presentations from the 2023 World Conference on Lung Cancer for which he served as discussant: the global landscape of three types of lung cancer (squamous cell, adenocarcinoma, and small cell); findings from the Australian Registry and Biobank of Thoracic Cancers; the Registry of Genetic Alterations of Taiwan by comprehensive next-generation sequencing; and treatment decisions in octogenarians with non-small cell lung cancer.
Xiuning Le, MD, PhD, of The University of Texas MD Anderson Cancer Center, discusses results of the VISION trial, the largest on-treatment liquid biopsy biomarker data set of a MET inhibitor in patients with MET exon 14 non–small cell lung cancer (NSCLC). Tepotinib showed durable efficacy in this population.
Ilias Houda, MD, PhD Candidate, of Amsterdam University Medical Centers, discusses the differing opinions of thoracic surgeons when it comes to resection for stage III non–small cell lung cancer (NSCLC). The international EORTC survey showed there is no consensus, although respondents were more likely to consider some stage III TNM combinations to be potentially resectable.
Seshiru Nakazawa, MD, PhD, of Dana-Farber Cancer Institute, discusses activating the MET tyrosine kinase domain mutation, which has been identified as the sole oncogenic mutation in a small but significant subset of patients with non–small cell lung cancer (NSCLC). According to Dr. Nakazawa’s findings, this mutation is potentially targetable with currently available MET tyrosine kinase inhibitors.
Shirish M. Gadgeel, MD, of the Henry Ford Cancer Institute, discusses a 5-year follow-up study of patients with metastatic non–small cell lung cancer (NSCLC) who were treated with pembrolizumab plus chemotherapy. According to Dr. Gadgeel, the findings continue to support the use of pembrolizumab plus chemotherapy as a standard-of-care first-line treatment, including in tumors with a PD-L1 tumor proportion scores of less than 1%.
Yasir Y. Elamin, MD, of The University of Texas MD Anderson Cancer Center, discusses findings from the BRIGHTSTAR study, in which brigatinib with local consolidative therapy was found to be safe in patients with ALK-rearranged advanced non–small cell lung cancer. This regimen yielded promising outcomes when compared with historical outcomes with brigatinib alone (Abstract OA22.04).
Chee K. Lee, PhD, MBBS, of the University of Sydney, discusses findings of the ILLUMINATE study, which showed durvalumab and tremelimumab with chemotherapy yielded antitumor activity in patients with non–small cell lung cancer (NSCLC) whose tumors progressed after receiving EGFR inhibitors. This result was especially marked in those with EGFR T790M–negative tumors (Abstract OA09.04).
David H. Harpole, Jr, MD, of Duke University Medical Center, discusses further exploratory analyses of patients with EGFR-mutated resectable non–small cell lung cancer (NSCLC) enrolled in the phase III AEGEAN study. In this trial, perioperative durvalumab plus neoadjuvant chemotherapy, vs neoadjuvant chemotherapy alone, significantly improved event-free survival and pathologic complete response (Abstract OA12.06).
Ticiana A. Leal, MD, of Winship Cancer Institute at Emory University, discusses phase III findings from the LUNAR study of tumor treating fields (electric fields that disrupt cellular processes and lead to cell death) combined with the standard of care in patients with metastatic non–small cell lung cancer (NSCLC) after relapse on platinum treatment. The survival benefit of this regimen was especially profound in patients with tumor PD-L1 expression who received an immune checkpoint inhibitor as the standard of care, according to Dr. Leal (Abstract OA22.05).
Tom E. Stinchcombe, MD, of Duke Cancer Institute, discusses an analysis of the rate of second primary lung cancer from the CALGB (Alliance) 140503 trial of lobar vs sublobar resection for T1a N0 non–small cell lung cancer (NSCLC). The data have implications for surveillance and screening strategies for patients with resected stage I disease (Abstract OA12.03).
Wei Wu, MD, PhD, of the University of California, San Francisco, discusses new findings that suggest his team’s deep learning neural network model may be able to identify subpopulations of patients with lung cancer who have YAP1-activated tumors and drug-tolerant persister cells. These patients may benefit most from receiving YAP1-targeted small-molecule inhibitors.
Narjust Florez, MD, of Dana-Farber Cancer Institute, and Ferdinandos Skoulidis, MD, PhD, of The University of Texas MD Anderson Cancer Center, discuss results of a biomarker subgroup analysis, showing that sotorasib demonstrated consistent clinical benefit vs docetaxel in all molecularly defined subgroups of patients with pretreated KRAS G12C–mutated advanced non–small cell lung cancer (NSCLC). Although no predictive biomarkers were confirmed, novel hypothesis-generating signals were observed (Abstract 9008).
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).
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).
James Chih-Hsin Yang, MD, PhD, of the National Taiwan University Hospital and National Taiwan University Cancer Center, discusses the latest data from the phase III KEYNOTE-789 study, which evaluated the efficacy and safety of pemetrexed plus platinum chemotherapy (carboplatin or cisplatin) with or without pembrolizumab in the treatment of adults with EGFR tyrosine kinase inhibitor–resistant, EGFR–mutated, metastatic nonsquamous non–small cell lung cancer (NSCLC) (Abstract LBA9000).
Penelope Bradbury, MBChB, of Canada’s Princess Margaret Cancer Centre, discusses phase III findings showing that, in patients with treatment-naive unresectable pleural mesothelioma, cisplatin and pemetrexed with pembrolizumab improved median overall survival with acceptable tolerability (Abstract LBA8505).
Jonathan W. Riess, MD, of the University of California, Davis Comprehensive Cancer Center, explores the findings of three important clinical trials in lung cancer treatment: whether to incorporate immune checkpoint inhibitors into the treatment of EGFR-mutated lung cancer, the importance of central nervous system activity in EGFR-mutant lung cancer, and new therapies for disease with EGFR exon 20 insertion.
Narjust Florez, MD, of Dana-Farber Cancer Institute, and Heather A. Wakelee, MD, of Stanford University, Stanford Cancer Institute, discuss new data supporting neoadjuvant pembrolizumab plus chemotherapy followed by surgery and adjuvant pembrolizumab as a promising new treatment option for patients with resectable stage II, IIIA, or IIIB (N2) non–small cell lung cancer (NSCLC) (Abstract LBA100).