Daraxonrasib Shows Antitumor Activity in Previously Treated RAS-Mutant NSCLC
Daraxonrasib produced responses in more than 30% of patients with previously treated advanced RAS-mutant non–small cell lung cancer (NSCLC), with activity observed across multiple RAS mutations in a phase I/II study. Results from Kathryn C. Arbour, MD, David S. Hong, MD, and colleagues were...
Tambotatug Pelitecan May Improve Survival Outcomes in Relapsed SCLC
The B7-H3–targeting antibody-drug conjugate tambotatug pelitecan significantly improved overall survival compared with topotecan in patients with small cell lung cancer (SCLC) that had progressed after first-line platinum-based therapy, according to results of the phase III TAISHAN-302 trial...
Germline EGFR T790M Associated With Significant Lung Cancer Risk
Researchers have found a significantly increased risk of lung cancer in individuals with an EGFR T790M germline variant, about 25 times higher than in noncarriers, according to study findings published in Science. “Today, lung cancer screening is driven almost entirely by smoking history,” said...
Second-Line Investigational Monoclonal Antibody in Metastatic Squamous NSCLC
Patients with metastatic squamous non–small cell lung cancer (NSCLC) whose disease progressed following PD-1/-L1 inhibitor therapy experienced a median overall survival of 18.5 months with the investigational anti–CTLA-4 antibody gotistobart compared with 10.0 months for patients receiving...
Julia Rotow, MD, on Metastatic HER2-Mutant NSCLC: First-Line T-DXd
Julia Rotow, MD, of Dana-Farber Cancer Institute, discusses the primary results from the phase III DESTINY-Lung04 trial, which evaluated first-line trastuzumab deruxtecan (T-DXd), a HER2-directed antibody-drug conjugate, against pembrolizumab plus platinum chemotherapy in patients with advanced/metastatic HER2-mutant non–small cell lung cancer (NSCLC) (Abstract PL03.08).
BRAF Class Alterations in NSCLC Have Different Characteristics, Outcomes, and Co-Mutations, Research Shows
Researchers have identified varying clinicopathologic characteristics and outcomes between patients with non–small cell lung cancer (NSCLC) and class II and III BRAF mutations, according to findings presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World...
Martin Reck, MD, PhD, on Resectable/Borderline Resectable NSCLC: Neoadjuvant Durvalumab Plus Chemotherapy
Martin Reck, MD, PhD, of LungenClinic Grosshansdorf, reviews efficacy and safety data from the primary analysis of MDT-BRIDGE. The phase II study is investigating perioperative durvalumab plus neoadjuvant chemotherapy in patients with resectable/borderline resectable stage IIB–IIIB non–small cell lung cancer (NSCLC) and evaluating whether chemoradiotherapy followed by consolidation durvalumab is effective and tolerable in patients who become unresectable during neoadjuvant treatment (Abstract OA04.02).
Mobile CT Lung Cancer Screening May Expand Access for Underserved Populations
Mobile low-dose computed tomography (LDCT) screening may be able to reach high-risk and socially vulnerable populations in resource-limited settings, according to initial results from the Third Brazilian Early Lung Cancer Trial (BRELT3) presented at the International Association for the Study of...
Alexander I. Spira MD, PhD, FACP, FASCO, on Metastatic EGFR-Mutated NSCLC: Global Study of Izalontamab Brenitecan
Alexander I. Spira MD, PhD, FACP, FASCO, of Virginia Cancer Specialists and US Oncology, discusses findings from a global phase I study of izalontamab brenitecan (BL-B01D1), an antibody-drug conjugate comprising an EGFR x HER3 bispecific antibody conjugated to a novel topoisomerase 1 inhibitor payload via a stable tetrapeptide-based cleavable linker. In a randomized dose-expansion cohort, the agent demonstrated promising efficacy with a tolerable safety profile in patients with previously treated EGFR-mutated non–small cell lung cancer (NSCLC) (Abstract OA10.01).
First-Line Amivantamab/Chemotherapy in EGFR Exon 20 Insertion–Positive Advanced NSCLC
Results from the phase III PAPILLON study show that first-line amivantamab plus carboplatin/pemetrexed (amivantamab/chemotherapy) was associated with numerically longer overall survival compared with chemotherapy in patients with previously untreated advanced non–small cell lung cancer (NSCLC)...
Tumor Budding Grading System Can Identify High-Risk Patients With Lung Squamous Cell Carcinoma
A tumor budding–based grading system was able to successfully identify patients with resected lung squamous cell carcinoma who were at a higher risk of poor overall survival and relapse-free survival outcomes, according to findings presented at the International Association for the Study of Lung...
FDA Approves New Labeling of ROS1 Inhibitor in TKI-Naive Advanced NSCLC
The U.S. Food and Drug Administration (FDA) has approved updated labeling of taletrectinib (Ibtrozi), an oral, CNS-active, selective next-generation ROS1 inhibitor therapy for non–small cell lung cancer (NSCLC), reflecting a median duration of response of 49.7 months in tyrosine kinase inhibitor...
First-Line Trastuzumab Deruxtecan Prolongs PFS in HER2-Mutant NSCLC
Trastuzumab deruxtecan significantly improved progression-free survival over pembrolizumab plus platinum-based chemotherapy for patients with advanced or metastatic HER2-mutant non–small cell lung cancer (NSCLC) who were being treated in the first-line setting, according to phase III DESTINY-Lung04 ...
Zipalertinib Added to Chemotherapy Improves Progression-Free Survival in First-Line EGFR Exon 20 Mutation–Positive NSCLC
The addition of zipalertinib to platinum/pemetrexed chemotherapy led to a significant improvement in progression-free survival in patients with advanced non–small cell lung cancer (NSCLC) harboring an EGFR exon 20 insertion mutation, according to phase III findings presented at the International...
Zidesamtinib Demonstrates 94% Response Rate in TKI-Naive Patients With Advanced ROS1-Positive NSCLC
New results from the global phase I/II ARROS-1 trial showed clinically meaningful activity with the ROS1 selective inhibitor zidesamtinib in patients with advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC) who had not previously received a tyrosine kinase inhibitor (TKI). The...
Chul Kim, MD, on NSCLC With EGFR Exon 20 Insertions: First-Line Amivantamab/Chemotherapy vs Chemotherapy
Chul Kim, MD, of Georgetown Cancer Institute, reviews findings from the phase III PAPILLON study, which found that first-line amivantamab plus carboplatin/pemetrexed was associated with numerically longer overall survival compared with chemotherapy alone in patients with previously untreated advanced non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations (Abstract PL03.03).
PD-L1–High Metastatic NSCLC: First-Line Sacituzumab Govitecan Plus Pembrolizumab Does Not Meet Progression-Free Survival Endpoint
Sacituzumab govitecan-hziy plus pembrolizumab did not demonstrate a statistically significant improvement in progression-free survival compared with pembrolizumab alone as first-line treatment for patients with metastatic non–small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score (TPS)...
Two Phase III Trials Explore B7-H3–Directed ADCs in Relapsed SCLC
Relapsed small cell lung cancer (SCLC) remains a major therapeutic challenge, with limited treatment options and poor outcomes after disease progression on platinum-based chemotherapy and immunotherapy. At the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on...
Long-Term Benefit Seen With Adjuvant Osimertinib in EGFR-Mutated NSCLC
An 8-year update of the phase III ADAURA trial showed that adjuvant osimertinib continued to demonstrate an overall survival benefit over placebo in patients with resected EGFR-mutated non–small cell lung cancer (NSCLC), according to findings presented at the International Association for the Study ...
Izalontamab Brenitecan Active in Previously Treated EGFR-Positive NSCLC
Izalontamab brenitecan (BL-B01D1), an EGFR x HER3 bispecific antibody, demonstrated antitumor activity and a tolerable safety profile, especially at higher dose levels, in patients with previously treated EGFR-mutated metastatic non–small cell lung cancer (NSCLC). These data from a randomized...
Ivonescimab Significantly Improves Overall Survival vs Pembrolizumab in PD-L1–Positive Advanced NSCLC
Ivonescimab, a first-in-class PD-1/VEGF bispecific antibody, was compared with pembrolizumab as first-line treatment for patients with PD-L1–positive advanced non–small cell lung cancer (NSCLC). Data from the prespecified interim analysis of the phase III HARMONi-2 trial were presented at the...
MAVERICK Trial Supports Brain MRI Surveillance Alone as Standard of Care for SCLC
Results from the international phase III SWOG S1827 MAVERICK trial show that brain magnetic resonance imaging (MRI) surveillance alone improved cognitive failure-free survival compared with MRI surveillance plus prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC)....
Chad G. Rusthoven, MD, on SCLC: Brain MRI Surveillance With or Without Prophylactic Cranial Irradiation
Chad G. Rusthoven, MD, of the University of Colorado School of Medicine, presents results from the international phase III SWOG S1827 MAVERICK trial, which showed that brain MRI surveillance alone improved cognitive failure–free survival compared with MRI surveillance plus prophylactic cranial irradiation in patients with small cell lung cancer (SCLC). The findings support MRI surveillance alone as the standard of care for patients with SCLC (Abstract PL02.01).
Roy S. Herbst, MD, PhD, on Resected EGFR-Mutated NSCLC: Long-Term Overall Survival With Osimertinib
Roy S. Herbst, MD, PhD, of Dartmouth Cancer Center, discusses 8-year overall survival data from the landmark ADAURA trial, which showed the sustained long-term benefit of adjuvant therapy with osimertinib for patients with completely resected, EGFR-mutated stage IB–IIIA non–small cell lung cancer (NSCLC) (Abstract PL03.01).
Alexander Drilon, MD, on Advanced Metastatic ROS1-Positive NSCLC: Zidesamtinib in TKI-Naive Patients
Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center, presents efficacy and safety data from a phase II cohort of the ARROS-1 trial, which included patients with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC) who were naive to tyrosine kinase inhibitor (TKI) therapy (Abstract PL03.06).
Adjuvant Alectinib Maintains Quality of Life During 2 Years of Treatment in Resected ALK-Positive NSCLC
Adjuvant alectinib was associated with early improvements in health-related quality of life that were maintained over 2 years of treatment in patients with resected ALK-positive non–small cell lung cancer (NSCLC). The new analysis of the phase III ALINA trial, reported by Dziadziuszko et al in The...
Extended-Interval Dosing of Tarlatamab Found Safe, Effective in SCLC
Extended-interval dosing of intravenous tarlatamab, at 20 mg every 3 weeks or 30 mg every 4 weeks, demonstrated efficacy and safety that was consistent with the approved tarlatamab dosing regimen in patients with small cell lung cancer (SCLC), according to findings from the phase II DeLLphi-309...
Favorable Safety Profile Found for Subcutaneous Tarlatamab in ES-SCLC
Subcutaneous administration of tarlatamab was well tolerated in patients with extensive-stage small cell lung cancer (ES-SCLC) in the phase IB DeLLphi-308 trial. Investigators were able to eliminate the preplanned post-dose monitoring in the second part of the study due to the safety of the...
Perioperative Atezolizumab Plus Chemotherapy Improves Outcomes in Resectable Stage II–IIIB NSCLC
Patients with resectable stage IIB–IIIB non–small cell lung cancer (NSCLC) treated with perioperative atezolizumab plus platinum-based chemotherapy experienced a median event-free survival of 62.8 months compared with 34.9 months for patients receiving chemotherapy alone. However, these results did ...
NSCLC: FDA Grants Accelerated Approval to Sevabertinib for Locally Advanced or Metastatic Nonsquamous Disease
Today, the U.S. Food and Drug Administration (FDA) granted accelerated approval to sevabertinib (Hyrnuo), a kinase inhibitor, for adult patients with locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) whose tumors have HER2 tyrosine kinase domain (TKD) activating...
Osimertinib Plus Chemotherapy Significantly Extends Progression-Free Survival in EGFR/TP53-Mutated NSCLC
Adding chemotherapy to first-line osimertinib more than doubled median progression-free survival in patients with advanced EGFR-mutated non–small cell lung cancer (NSCLC) harboring concurrent TP53 mutations. The findings come from a phase III randomized trial led by Zhou et al and published in...
Radiation to the Thymus in NSCLC Treatment May Increase Risk of Metastasis
Radiation to the thymus was found to be associated with worse outcomes in patients with non–small cell lung cancer (NSCLC), leading to an increased risk of metastasis, according to findings published in the Annals of Oncology. “The thymus is currently not routinely treated as an important organ...
Living Guideline Adds Repotrectinib and Zongertinib as Treatment Options for Advanced NSCLC With Driver Alterations
ASCO has issued a new update to its Living Guideline on therapy for stage IV non–small cell lung cancer (NSCLC) with driver alterations, including new recommendations for two therapies: repotrectinib, a ROS1 tyrosine kinase inhibitor (TKI), and zongertinib, a HER2-selective, EGFR-sparing TKI.1 The...
First-in-Class Bispecific ADC Shows Activity in Relapsed Extensive-Stage Small Cell Lung Cancer
In a phase Ib study published in the Journal of Clinical Oncology, Zhao et al found that the first-in-class bispecific antibody-drug conjugate (ADC) izalontamab brengitecan (iza-bren, BL-B01D1), which targets EGFR and HER3, demonstrated antitumor activity in patients with relapsed extensive-stage...
Durvalumab Plus Radiation Therapy in Frail Patients With Locally Advanced NSCLC
In a phase II study published in the Journal of Clinical Oncology, Rimner et al found that concurrent and consolidative durvalumab administered with definitive radiation therapy, without chemotherapy, demonstrated encouraging efficacy in patients with inoperable locally advanced non–small cell lung ...
When Diagnosis Waits: Lung Cancer, PET Access, and Global Oncology
A few weeks ago, a friend in the United States reached out to me about her sister in Rwanda, a woman in her 40s with no history of smoking. Her chest pain had progressively worsened to the point of becoming unbearable. CT imaging revealed a concerning lung mass highly suggestive of malignancy. One...
ELEVATE Trial Shows Disease-Free Survival Benefit With Adjuvant Ensartinib in ALK-Positive NSCLC
In an interim analysis of the phase III ELEVATE trial reported in The New England Journal of Medicine, Yue et al found that patients with completely resected ALK-positive non–small cell lung cancer (NSCLC) who received adjuvant ensartinib experienced significantly longer disease-free survival than...
Proton Pump Inhibitor, Antibiotic Exposure Linked to Inferior Durvalumab Outcomes in Unresectable Stage III NSCLC
As reported in The Lancet Oncology by Brunetti et al, a post hoc analysis of the phase III PACIFIC trial showed that baseline exposure to proton pump inhibitors and antibiotics was associated with inferior outcomes among patients with unresectable stage III non–small cell lung cancer (NSCLC)...
Access Denied: Insurance Barriers to Biomarker Testing in Lung Cancer
In the past few decades, the rapidly growing field of precision medicine has improved the survival of patients with lung cancer. Yet the benefits of these therapies do not reach all patients. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, yet most patients are diagnosed ...
Paraneoplastic Neurological Syndromes Associated With Improved Survival in SCLC
Patients with small cell lung cancer (SCLC) and type 1 antineuronal nuclear or “Hu” antibody (ANNA1/Hu-IgG)–related paraneoplastic neurological syndromes (PNS) may experience longer survival, according to the results of a study published in Journal of Neurology. Additionally, in those with...
FDA Approves Zidesamtinib for Second-Line Treatment of ROS1-Positive NSCLC
On July 22, the U.S. Food and Drug Administration (FDA) approved zidesamtinib (Jideytro), a ROS1 selective inhibitor, for the treatment of adult patients with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC) who received a prior ROS1 kinase inhibitor. The approval...
Can Consolidative Thoracic Radiotherapy Improve Outcomes During Immunotherapy Maintenance in Extensive-Stage SCLC?
Consolidative thoracic radiotherapy added to standard maintenance immunotherapy increased toxicity without improving survival in first-line extensive-stage small cell lung cancer (SCLC), according to findings from the multicenter phase II TREASURE (AIO-TRK-0320) trial published in JAMA Oncology....
Emergency Department Cancer Diagnosis Associated With Higher Mortality Across 16 Cancer Types
Diagnosis of a cancer upon emergency department presentation was associated with an elevated mortality rate, which was consistent across 16 analyzed cancer types, according to new research findings published in the Journal of the National Cancer Institute. “These gaps held up even after we...
Benjamin P. Levy, MD, on Emerging Options for KRAS G12C–Mutated NSCLC: First-Line and Combination Therapies
Benjamin P. Levy, MD, of Johns Hopkins Sidney Kimmel Cancer Center, discusses research into moving KRAS G12C inhibitors from the second to the first line, as well as combining them with immunotherapies and EGFR antibodies. Some potential combinations under investigation include KRAS G12C inhibitors (such as olomorasib, fulzerasib, divarasib, and adagrasib) and single-agent immunotherapy (pembrolizumab) or EGFR-targeting therapies (cetuximab).
Benjamin P. Levy, MD, on KRAS G12C–Mutated NSCLC: Current Treatment Landscape
Benjamin P. Levy, MD, of Johns Hopkins Sidney Kimmel Cancer Center, reviews currently available therapies for patients with KRAS G12C–mutated non–small cell lung cancer (NSCLC), noting the importance of genomic testing to identify individuals eligible for treatment with these agents. He discusses the two FDA-approved second-line drugs in this space—sotorasib and adagrasib—touching on their efficacy and associated adverse events. He also mentions divarasib, an investigational next-generation KRAS G12C inhibitor, which showed superiority over both sotorasib and adagrasib in a recent head-to-head phase III trial.
Overall Survival With Ivonescimab or Tislelizumab Plus Chemotherapy in Advanced Squamous NSCLC
As reported in The Lancet by Lu et al, an interim analysis of the Chinese phase III HARMONi-6 trial showed that ivonescimab plus chemotherapy was associated with significantly improved overall survival vs tislelizumab plus chemotherapy in patients with previously untreated advanced squamous...
Addition of Sacituzumab Tirumotecan to Pembrolizumab in PD-L1–Positive Advanced NSCLC
As reported in The Lancet by Xiong et al, an interim analysis of a Chinese phase III trial (OptiTROP-Lung05) has shown that the addition of sacituzumab tirumotecan (a trophoblast cell–surface antigen 2–targeting antibody-drug conjugate) to pembrolizumab significantly prolonged progression-free...
FDA Grants Traditional Approval to Selpercatinib for Locally Advanced or Metastatic RET Fusion–Positive Solid Tumors
On July 14, the U.S. Food and Drug Administration (FDA) granted traditional approval to selpercatinib (Retevmo), an oral RET inhibitor, for adult and pediatric patients aged 2 years and older with locally advanced or metastatic solid tumors with a RET gene fusion, as detected by an FDA-approved...
Case 3: Second-Line Treatment of Extensive-Stage Small Cell Lung Cancer
This is Part 3 of Integrating Immunotherapy Across the SCLC Spectrum, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Laura Alder, MD, Noura Choudhury, MD, and Alissa Cooper, MD, discuss second-line treatment of extensive-stage small cell lung cancer (SCLC). The patient is a 65-year-old man with extensive-stage SCLC who had a good initial partial response to carboplatin, etoposide, and atezolizumab followed by atezolizumab maintenance. On routine surveillance imaging, however, he is found to have new brain metastases along with progressive disease in the chest and liver. The faculty highlight the growing role of tarlatamab in the second-line setting, practical considerations around monitoring for cytokine-release syndrome and neurologic toxicity, the importance of prioritizing clinical trials at every stage of care, and decision-making around managing brain metastases with radiation vs systemic therapy.
Case 2: De Novo Extensive-Stage Small Cell Lung Cancer
This is Part 2 of Integrating Immunotherapy Across the SCLC Spectrum, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Laura Alder, MD, Noura Choudhury, MD, and Alissa Cooper, MD, discuss the management of de novo extensive-stage small cell lung cancer. The patient is a 58-year-old man who presents with worsening dyspnea, weight loss, and fatigue. He is found to have a large lung mass with liver and adrenal metastases as well as several small, asymptomatic brain metastases. Liver biopsy confirms the diagnosis of small cell lung cancer. The faculty highlight how to approach initial conversations around diagnosis and prognosis, the value of early palliative care involvement, and the standard-of-care chemoimmunotherapy backbone established by the IMpower133 and CASPIAN trials. They also discuss management of small brain metastases, the emerging role of the IMforte regimen, and considerations around consolidative vs concurrent thoracic radiotherapy in this setting.
