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®, Jacob Sands, MD, assistant professor of Medicine at Harvard Medical School, thoracic oncologist at the Dana-Farber Cancer Institute, and investigator of the 

phase 2 TROPION-Lung05 trial (NCT04484142)

phase 3 TROPION-Lung01 trial (NCT04656652)

accelerated approval of datopotamab deruxtecan-dlnk

mutant metastatic NSCLC in June 2025, discussed safety and efficacy considerations for the agent’s use.

He began by outlining a combined cohort of the TROPION-Lung05 and TROPION-Lung01 trials, which collectively showed an efficacy benefit with dato-DXd in patients with 

mutant disease vs docetaxel. In the combined cohort, the median progression-free survival with dato-DXd reached 5.8 months, and the median overall survival was 15.6 months. Additional efficacy data revealed an objective response rate of 45% (95% CI, 35%-54%) and a median duration of response of 6.5 months (95% CI, 4.2-8.4).

Furthermore, Sands highlighted the most common toxicities observed with dato-DXd in this population, which included stomatitis, interstitial lung disease, and ocular toxicities. He also reviewed management strategies to mitigate their incidence and severity. Specifically, remedies include prophylaxis, oral hygiene, and dose reductions for stomatitis; using preservative-free eye drops and ophthalmology visits for ocular toxicity management and prevention; and monitoring for any incidence of high-grade ILD.

He then touched upon next steps for research in this disease state, including the phase 2 ORCHARD trial (NCT03944772) evaluating dato-DXd with osimertinib (Tagrisso) in the second-line setting after progression on osimertinib and the phase 3 TROPION-Lung15 trial (NCT06417814), which is evaluating chemotherapy vs dato-DXd alone or with osimertinib.

Sands concluded by discussing the implications for toxicity management in patients who experience responses that exceed median outcomes, suggesting that the toxicity profile may be more severe for this group. Emphasizing the broadness of outcomes with any drug, he expressed that patients with experiences that deviate from the observed median outcome are an important consideration for clinical practice.

Sands J, Ahn MJ, Lisberg A, et al. Datopotamab deruxtecan in advanced or metastatic non-small cell lung cancer with actionable genomic alterations: results from the phase II TROPION-Lung05 study. 

. Published online January 6, 2025. doi:10.1200/JCO-24-01349

Ahn MJ, Tanaka K, Paz-Ares L, et al. Datopotamab deruxtecan versus docetaxel for previously treated advanced or metastatic non-small cell lung cancer: the randomized, open-label phase III TROPION-Lung01 study. 

. Published online September 9, 2024. doi:10.1200/JCO-24-01544

FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer. News release. FDA. June 23, 2025. Accessed July 29, 2025. https://tinyurl.com/mtay7ab9

Yu HA, Goldberg SB, Le X, et al. Biomarker-directed phase II platform study in patients with EGFR sensitizing mutation-positive advanced/metastatic non-small cell lung cancer whose disease has progressed on first-line osimertinib therapy (ORCHARD). 

. 2021;22(6):601-606. doi:10.1016/j.cllc.2021.06.006

A study to investigate the efficacy and safety of dato-DXd with or without osimertinib compared with platinum based doublet chemotherapy in participants with EGFR-mutated locally advanced or metastatic non-small cell lung cancer (TROPION-Lung15). ClinicalTrials.gov. Updated July 16, 2025. Accessed July 29, 2025. https://tinyurl.com/56z3dmsp

Dato-DXd in Pretreated EGFR-Mutated Metastatic NSCLC

Jacob Sands, MD, discussed considerations for EGFR-mutant non–small cell lung cancer following the approval of dato-DXd in this disease.

Integrating Dato-DXd Into Early-Line EGFR-Mutant NSCLC Management

2025 American Society of Clinical Oncology (ASCO) Annual Meeting

, CancerNetwork® put together an X Spaces discussion hosted by Stephen Liu, MD; and Joshua Sabari, MD, to highlight the most intriguing and practice-changing lung cancer abstracts. Discussed topics ranged from long-term follow-up with commonplace therapies to an analysis of what time of day is best to administer immunochemotherapy.

Liu, an associate professor of medicine at Georgetown University and the director of thoracic oncology and head of developmental therapeutics at the Georgetown Lombardi Comprehensive Cancer Center, and Sabari, an assistant professor in the Department of Medicine at the New York University Grossman School of Medicine and the director of high reliability organization initiatives at the Perlmutter Cancer Center, shared expert insights on the latest non–small cell lung cancer (NSCLC) and SCLC breakthroughs.

Trials of note that they discussed included:

The phase 3 DeLLphi-304 trial (NCT05740566)

: "Tarlatamab (Imdelltra) vs Chemotherapy (CTx) as Second-Line (2L) Treatment for Small Cell Lung Cancer (SCLC): Primary Analysis of Ph3 DeLLphi-304"

: "Lurbinectedin (Lurbi) + Atezolizumab (Atezo) as First-Line (1L) Maintenance Treatment (tx) in Patients (pts) With Extensive-Stage Small Cell Lung Cancer (ES-SCLC): Primary Results of the Phase 3 IMforte Trial"

The phase 3 CheckMate 816 trial (NCT02998528)

: "Overall Survival With Neoadjuvant Nivolumab (NIVO) + Chemotherapy (Chemo) in Patients With Resectable NSCLC in CheckMate 816"

The phase 3 PACIFIC15 trial (NCT05549037): "Randomized Trial of Relevance of Time-of-Day of Immunochemotherapy for Progression-Free and Overall Survival in Patients With Non–Small Cell Lung Cancer"

The phase 3 Beamion LUNG-1 trial (NCT04886804): "Patient-Reported Outcomes (PRO) Evaluating Physical Functioning and Symptoms in Patients With Pretreated HER2-Mutant Advanced Non-Small Cell Lung Cancer (NSCLC): Results From the Beamion LUNG-1 trial"

The phase 3 ARTEMIA trial (NCT06472245): "Phase 3 Trial of the Therapeutic Cancer Vaccine OSE2101 Versus Docetaxel in Patients With Metastatic Non-Small Cell Lung Cancer and Secondary Resistance to Immunotherapy"

Rudin C, Mountzios G, Sun L, et al. Tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): primary analysis of ph3 DeLLphi-304. 

. 2025;43(suppl 17):LBA8008. doi:10.1200/JCO.2025.43.17_suppl.LBA8008

Paz-Ares L, Borghaei H, Liu SV, et al. Lurbinectedin (lurbi) + atezolizumab (atezo) as first-line (1L) maintenance treatment (tx) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC): primary results of the phase 3 IMforte trial. 

2025;43(suppl 16):8006. doi:10.1200/JCO.2025.43.16_suppl.8006

Forde PM, Spicer JD, Provencio M, et al. Overall survival with neoadjuvant nivolumab + chemotherapy in patients with resectable NSCLC in CheckMate 816. 

. 2025;43(suppl 17):LBA8000. doi:10.1200/JCO.2025.43.17_suppl.LBA8000

Zhang Y, Huang Z, Zeng L, et al. Randomized trial of relevance of time-of-day of immunochemotherapy for progression-free and overall survival in patients with non-small cell lung cancer. 

. 2025;43(suppl 16):8516. doi:10.1200/JCO.2025.43.16_suppl.8516

Sabari JK, Nadal E, Hendriks L, et al. Patient-reported outcomes (PRO) evaluating physical functioning and symptoms in patients with pretreated HER2-mutant advanced non-small cell lung cancer (NSCLC): results from the Beamion LUNG-1 trial. 

2025;43(suppl 16):8620. doi:10.1200/JCO.2025.43.16_suppl.8620

Liu SV, Guibert C, Tostivint EP, et al. Phase 3 trial of the therapeutic cancer vaccine OSE2101 versus docetaxel in patients with metastatic non-small cell lung cancer and secondary resistance to immunotherapy. 

. 2025;43(suppl 16):TPS8651. doi:10.1200/JCO.2025.43.16_suppl.TPS8651

ASCO Annual Meeting: Lung Cancer

Stephen Liu, MD; and Joshua Sabari, MD, discuss the most intriguing non–small cell lung cancer and small cell lung cancer breakthroughs from the meeting. 

Practice-Changing Lung Cancer Data From the 2025 ASCO Annual Meeting

In the third edition of a special podcast series, CancerNetwork

 spoke with Daniel Morgensztern, MD; Mary Ellen Flanagan, NP; and Janelle Mann, PharmD, BCOP, about optimal strategies for incorporating different therapeutic agents into lung cancer care. As part of the latest discussion, the group highlighted the relevant efficacy data, administration protocols, and toxicity management considerations associated with TROP2-directed antibody-drug conjugates (ADCs) in patients with non–small cell lung cancer (NSCLC).

Morgensztern is a professor of medicine and the clinical director of thoracic oncology in the Division of Oncology at Washington University School of Medicine in St Louis. Flanagan is a nurse practitioner in the Division of Thoracic Oncology at Washington University. Mann is a clinical oncology pharmacist at Siteman Cancer Center of Washington University School of Medicine and manager of clinical pharmacy services at Barnes-Jewish Hospital.

Morgensztern opened the discussion by highlighting the characteristics of prominent TROP2-targeting ADCs in NSCLC management, which included sacituzumab govitecan-hziy (Trodelvy), datopotamab deruxtecan-dlnk (Datroway), and sacituzumab tirumotecan (sac-TMT). Additionally, he reviewed data from clinical trials assessing these ADCs across different NSCLC populations, including the phase 3 EVOKE-01 trial (NCT05089734) showing a numerical overall survival improvement with sacituzumab govitecan vs docetaxel.

Regarding the safety profiles of these ADCs, Flanagan described the unique toxicities associated with the agents’ payloads as well as potential off-target effects. On top of myelosuppression, fatigue, and diarrhea, she stated that these therapies may cause more visceral organ toxicities such as keratitis of the eye and interstitial lung disease. According to Flanagan, some prophylactic measures in the event of certain toxicities include frequent salt and baking soda mouth rinses as well as oral dexamethasone.

Mann then outlined the dosing variability considerations and supportive care measures surrounding the use of agents such as sacituzumab govitecan. She emphasized continuously re-educating patients about expected toxicities and supportive care strategies as they undergo these infusion-based therapies to help avoid surprise instances of ocular toxicity, diarrhea, and other adverse effects.

Paz-Ares LG, Juan-Vidal O, Mountzios GS, et al. Sacituzumab govitecan versus docetaxel for previously treated advanced or metastatic non-small cell lung cancer: the randomized, open-label phase III EVOKE-01 study. 

. 2024;42(24):2860-2872. doi:10.1200/JCO.24.00733

Experts from Washington University in St Louis discuss dosing considerations and toxicity management strategies for TROP2-targeted ADCs in NSCLC.

Adopting Best Practices for Administering TROP2-Directed ADCs in NSCLC

, Leticia Nogueira, PhD, MPH, highlighted the 

findings and implications of a study she published

 that evaluated how exposure to wildfires affected post-operative length of stay (LOS) among patients who were recovering from surgery for non–small cell lung cancer (NSCLC). Data from this study showed that patients who underwent curative-intent surgery at facilities exposed to a wildfire disaster experienced a longer LOS compared with similar patients who received treatment during times when no disasters occurred.

Journal of the National Cancer Institute, 

the LOS was 7.45 days (SE, 0.22) for patients treated at facilities without wildfire exposure vs 9.42 days (SE, 0.25) among those who underwent surgery at facilities with exposure (

 <.0001). Sensitivity analyses showed no significant difference for in-hospital mortality among patients with (10.5%) or without wildfire exposure (10.8%; 

According to Nogueira, scientific director of Health Services Research at the American Cancer Society, future research may further assess whether a longer LOS may impact survival among this patient population. Additionally, other efforts may focus on determining strategies for protecting the health and safety of patients during a climate disaster.

Describing an “inescapability” of climate or environmental hazards across all populations, Nogueira emphasized the importance of collaboration among different medical and research institutions to improve disaster preparedness and mitigation strategies. These shared efforts may reduce the impact of wildfires and similar climate hazards across treatment facilities and patient populations.

“We know that disasters are becoming more common. We know that their frequency, their intensity, and their behavior continue to change. The only way that we can figure out what’s going to work and what’s going to improve quality of care and patient outcomes is knowledge,” Nogueira stated. “Prioritizing this type of research and understanding that all of us are a patient at some point, that we are all eventually vulnerable, [is important].”

Nogueira LM, Yabroff KR, Yates E, Shultz JM, Valdez RB, Nori-Sarma A. Facility exposure to wildfire disasters and hospital length of stay following lung cancer surgery. 

. Published online March 11, 2025. doi:10.1093/jnci/djaf040

The “inescapability” of climate hazards may necessitate prioritization of research to improve outcomes among vulnerable populations who require treatment.

Improving NSCLC Surgery Recovery After Climate Disaster Exposure

In the first edition of a special podcast series, CancerNetwork

 spoke with Daniel Morgensztern, MD; Mary Ellen Flanagan, NP; and Janelle Mann, PharmD, BCOP, about best practices for implementing recently approved bispecific antibodies into cancer care. Their initial discussion focused on the clinical trial results, administration protocols, and toxicity management strategies related to the use of amivantamab-vmjw (Rybrevant) for patients with 

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

Morgensztern is a professor of Medicine and clinical director of Thoracic Oncology in the Division of Oncology at Washington University School of Medicine in St. Louis. Flanagan is a nurse practitioner in the Division of Thoracic Oncology at Washington University in St. Louis. Mann is a clinical oncology pharmacist at Siteman Cancer Center of Washington University School of Medicine in St. Louis and manager of Clinical Pharmacy Services at Barnes-Jewish Hospital.

Morgensztern began by giving an overview of amivantamab’s mechanism of action and highlighting supporting data for the agent when administered alone or in combination with other agents.

The FDA initially approved amivantamab monotherapy for patients with 

exon 20 insertion–mutant NSCLC in May 2021 based on data from the phase 1 CHRYSALIS trial (NCT02609776).

agency approved amivantamab/chemotherapy as frontline treatment for patients with NSCLC

exon 20 insertion mutations in March 2024 based on data from the phase 3 PAPILLON trial (NCT04538664).

Findings from the phase 3 MARIPOSA trial (NCT04487080) also supported the 

FDA approval of amivantamab plus lazertinib

Additionally, Mann reviewed key dosing considerations as patients receive amivantamab via intravenous infusion. She detailed the use of premedication such as diphenhydramine (Benadryl) to supplement amivantamab while monitoring for toxicities during the initial infusion period, which may necessitate additional dosing adjustments. Flanagan added to the conversation surrounding infusion-related reactions by describing strategies for mitigating the risk of venous thromboembolism, cutaneous toxicities, and other adverse effects.

 (amivantamab-vmjw) receives FDA approval as the first targeted treatment for patients with non-small cell lung cancer with EGFR exon 20 insertion mutations. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. May 21, 2021. Accessed January 29, 2025. https://tinyurl.com/3d8wtu4m

FDA approves amivantamab-vmjw for EGFR exon 20 insertion-mutated non-small cell lung cancer indications. News release. FDA. March 1, 2024. Accessed January 29, 2025. https://tinyurl.com/msw4u5yk

RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) approved in the U.S. as a first-line chemotherapy-free treatment for patients with EGFR-mutated advanced lung cancer. News release. Johnson & Johnson. August 20, 2024. Accessed January 29, 2025. https://tinyurl.com/yxc8u8t4

Experts from Washington University in St. Louis discuss trial results and infusion-related reaction management for amivantamab in EGFR-mutated NSCLC.

Navigating Management and Dosing Considerations for Amivantamab in NSCLC

, Terence T. Sio, MD, MS, discussed how technological advancements in radiation oncology have impacted the modern treatment landscape for patients with non–small cell lung cancer (NSCLC).

Sio, a professor of radiation oncology at Mayo Clinic in Phoenix, Arizona, first outlined the use of immunotherapy and other systemic treatment options for this patient population. He detailed how the use of these modalities and other factors such as the risk of radiation-induced pneumonitis often inform the extent of subsequent radiotherapy. Treatment decision making may also involve collaboration with surgeons and medical oncologists as part of a multidisciplinary tumor board, which meets regularly at his institution to determine suitable strategies for those who require more than 1 course of therapy.

Additionally, Sio spoke about currently prevalent radiotherapy treatment strategies for patients with NSCLC as well as possible toxicities that may be associated with these modalities. In terms of novel technology in the field, he highlighted the development of proton beam radiotherapy and the potential advantages it may offer over other therapies.

According to Sio, use of proton beam radiotherapy may reduce excess radiation that usually extends beyond the targeted tumor, effectively lowering the risk of adverse effects (AEs) during treatment. Specifically, proton beam radiotherapy may benefit patient subgroups including those who have previously experienced a heart attack or those who are older and frailer. With an adequate treatment plan that encompasses the use of proton beam radiation, Sio stated that it may be possible to treat these subgroups with fewer AEs than those observed in patients who undergo standard radiotherapy.

“We can actually be helping some of the patients who otherwise may not be able to stand as intensive of a method of combining radiation and chemotherapy for their lung cancer treatments,” Sio said regarding the use of proton beam radiotherapy in this population. “Right now, we have shown that proton [beam radiotherapy] has a role in lung cancer treatments.”

Terence T. Sio, MD, MS, highlights advances such as proton beam radiotherapy that may improve outcomes for those with non–small cell lung cancer.

Optimizing NSCLC Outcomes Via Technological Advances in Radiation Oncology

The robotic-assisted biopsy platform Ion is a “game-changer” for patients with lung cancer, as it provides a quicker, less invasive surgical method for conducting a lung biopsy, according to Richard Lazzaro, MD.

, Lazzaro, the chief of Thoracic Surgery at the Southern Region of RWJBarnabas Health, spoke about his experience with adopting the Ion robotic bronchoscopy platform for the early detection of lung cancer at Monmouth Medical Center. He highlighted how the tool may enable practices to acquire tissue and perform disease staging with fewer complications, which may particularly benefit those who plan to undergo induction chemotherapy or immunotherapy.

In terms of other potential advancements in the lung cancer surgery field, Lazzaro discussed how he anticipates the use of video-assisted thoracoscopic (VATS) surgery to evolve. Specifically, he mentioned the development of technologies such as augmented reality as tools that may help minimize the variability of surgical procedures.

Regarding his practice, Lazzaro highlighted how a multidisciplinary thoracic tumor board—including medical oncologists, radiologists, pathologists, and pulmonary physicians, among others—has helped in producing long-term survival improvements. He emphasized collective discussions and shared decision-making as part of determining appropriate courses of care for his patients. When it comes to a multidisciplinary approach, Lazzaro stated that “you want to take care of patients” like they were part of “your family.”

Overall, Lazzaro noted how the lung cancer treatment landscape has changed over time. He emphasized referring patients for CT scans as well as evaluations at nodule or thoracic oncology clinics as part of a multidisciplinary strategy.

“The management of lung cancer is different than it was even 5 years ago. If we can detect lung cancer early, we have options for treating patients today that we never had before,” Lazzaro said. “This is the time where we really need to make a huge difference in lung cancer.”

Richard Lazzaro, MD, discusses how a robot-assisted platform has impacted his thoracic surgery and highlights other potential advancements in the field.

Non-Small Cell Lung Cancer (NSCLC)

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