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The annual meeting of the American Society of Clinical Oncology (ASCO) once again brought together nearly 50,000 members of the oncology community. From May 30 – June 2, researchers, oncologists, and patient advocates had first-hand access to the latest cancer research news.
The theme for the 2025 ASCO conference was “Driving Knowledge to Action: Building a Better Future.” This theme was represented through several presentations during the conference that showcased how the cancer community is leveraging artificial intelligence (AI) to quickly and efficiently turn our extensive knowledge and experience into lifesaving interventions for patients.
Throughout the conference, researchers presented data on many aspects of lung cancer research and treatment. Below are some of the most impactful and interesting lung cancer studies presented at this meeting.
Highlights from the 2025 ASCO conference:
- Improvements in treating SCLC after it returns
- Neoadjuvant (before surgery) therapy is here to stay
- Progress on using antibody-drug conjugates (ADCs) to treat brain metastasis
- Developing more targeted treatment options for EGFR, KRAS, and HER2 lung cancers
Small Cell Lung Cancer – Evolving the Standard of Care
Currently, extensive-stage small cell lung cancer (SCLC) is often treated initially with a combination of immunotherapy and chemotherapy. Many patients benefit from this treatment, but the cancer is known to return aggressively.
The phase 3 DeLLphi-304 trial studied tarlatamab (a bispecific T-cell engager that targets overexpressed DLL3 in SCLC) as a possible alternative to chemotherapy for people whose cancers have relapsed. Tarlatamab reduced the risk of death by 40% compared to chemotherapy. This exciting finding marks a major milestone as a new standard of care for SCLC and provides much-needed hope for people whose tumors have started to grow after initial treatment.
Researchers have also been looking for a way to extend the initial benefits of first-line treatment and keep the cancer at bay. The phase 3 IMforte trial offers an option for first-line maintenance therapy for SCLC after initial treatment with immunotherapy and chemotherapy. The study showed that treating patients with atezolizumab (an anti-PD-L1 immunotherapy) plus lurbinectedin (an alkylating agent that disrupts transcription in cancer cells) after initial treatments improved overall survival by approximately 3 months.
Through the development of new therapeutic options and the implementation of cutting-edge technology, researchers are pursuing many avenues of study to improve outcomes for people living with SCLC.
Resectable Non-Small Cell Lung Cancer – Neoadjuvant Therapy Is Here to Stay!
Therapies that were initially developed for metastatic disease (cancer that has spread) are now being used to treat earlier stages of disease. They offer improved survival benefits for people with lung cancer but also raise new questions. With the possibilities of neoadjuvant (before surgery) treatment and also adjuvant (after surgery) treatment, these questions are top of mind:
- Is neoadjuvant treatment enough?
- Who needs adjuvant treatment? And for how long?
There has been a lot of discussion in the field about the timing and sequencing of treatments for people with early-stage disease that requires surgery. Understanding the effectiveness of neoadjuvant treatments and identifying patients who may need more aggressive treatment after surgery will help address some of these open questions.
In 2022, data showed the addition of neoadjuvant nivolumab (an immunotherapy that targets PD-1) could improve outcomes for those with resectable (can be removed with surgery) non-small cell lung cancer (NSCLC). At the ASCO meeting, we saw final results from CheckMate 816, a phase 3 trial that compared neoadjuvant chemotherapy plus nivolulmab to neoadjuvant chemotherapy alone in people with resectable NSCLC. The five-year overall survival rates increased by approximately 10% with the addition of neoadjuvant nivolumab.
In addition, the researchers found that people with a pathological complete response (no signs of cancer in the tissue samples after treatment with neoadjuvant nivolumab plus chemotherapy) had a 90% reduction in their mortality risk compared to those with evidence of residual disease. This finding may help predict the effectiveness of this neoadjuvant combination and guide adjuvant treatment planning based on a patient’s pathological complete response status.
These findings, and others like them, are helping bring clarity to the roles of neoadjuvant and adjuvant treatment approaches.
Treating Brain Metastasis in NSCLC – ADCs Advance the Field
Leptomeningeal disease (LMD) and brain metastasis are common in people with lung cancer and other types of solid tumors. Researchers have studied many different options for treating tumors that have spread to the central nervous system (CNS). ADCs, or antibody-drug conjugates, are an exciting new class of drugs that are a combination of targeted therapy and chemotherapy. ADCs act like a “smart chemotherapy” that delivers the drug compound directly to cancer cells, reducing harm to healthy tissue.
Preliminary data has shown some ADCs, such as datapotomab deruxtecan (a TROP2-directed ADC), trastuzumab deruxtecan (HER2-directed ADC), and infinatamab deruxtecan (a B7-H3 directed ADC), have caused CNS tumors to shrink in people with NSCLC and SCLC.
Data from a phase 2 clinical trial demonstrated the effect of HER3-DXd, a HER3-directed ADC, on people with LMD from any solid tumor and on people with brain metastasis from advanced NSCLC. The results showed that brain tumors shrank in 25% of people with advanced NSCLC. For those with LMD, 55% were alive three months after treatment. The treatment offered people improved quality of life and reduced neurological symptoms. While additional studies are ongoing, these results suggest ADCs may prove to be an effective approach for treating LMD and brain metastasis.
Oncogene-Driven NSCLC – Advancing Targeted Treatment Approaches
Classic EGFR Mutations (Ex19del or L858R)
Osimertinib has been the gold standard tyrosine kinase inhibitor (TKI) for treating metastatic NSCLC with classic EGFR mutations. As other treatments for metastatic disease are being considered for early-stage cancers, researchers have also looked at using osimertinib to treat resectable EGFR+ NSCLC.
Researchers presented results of NEOADAURA, a global phase 3 study that aimed to understand how to use osimertinib before surgery when treating resectable EGFR+ NSCLC. This three-armed study compared:
- Osimertinib plus chemotherapy
- Osimertinib alone
- Chemotherapy alone
Though full test results are pending, the initial data looks promising to use osimertinib before surgery, either in combination with chemotherapy or alone.
MET amplification is a common mechanism of resistance in tumors treated with EGFR-directed TKIs. It can be detected by tissue or liquid biopsy when cancer begins to grow again after treatment. To overcome this resistance, researchers aimed to use a combination of two TKIs (savolitinib and osimertinib) to target MET and EGFR respectively after disease progression on EGFR-targeted TKI in the phase 3 SACHI trial. The study compared the effectiveness of combining savolitinib and osimertinib versus chemotherapy in EGFR+ and METamp+ advanced NSCLC. The median overall survival of 22.9 months in the combination arm compared well to the median overall survival of 17.7 months in the chemotherapy arm. The results of this study emphasize the importance of rebiopsy at the time of disease progression to understand the mechanism of resistance and optimize treatment planning.
Researchers also studied savolitinib and osimertinib with the goal of understanding the role of savolitinib in the combination regimen and to study the effectiveness of targeting CNS metastasis with the combination treatment. The researchers compared results of savolitinib plus osimertinib with savolitinib alone and found the combination treatment demonstrated encouraging CNS activity and provided 8.3 months of median progression-free survival compared to 3.6 months on savolitinib alone. These studies will continue in the international phase 3 SAFFRON study that is open and currently enrolling patients.
EGFR Exon20 Insertions
When treating NSCLC with EGFR exon20 insertions, there is currently one approved targeted therapy. Amivantamab is a bispecific T-cell engager that binds to both EGFR and MET and is administered intravenously. In the first-line setting, amivantamab is combined with chemotherapy, and it can be used as monotherapy in the second line setting.
We saw data demonstrating the effectiveness of an emerging oral TKI, zipalertinib, for patients with EGFR exon20 ins+ NSCLC. The study included a group that was treated after chemotherapy and a group that was previously treated with chemotherapy or an exon20-targeted drug (such as poziotinib, mobocertinib, or amivantamab).
In the group treated with prior chemotherapy, the percentage of patients whose tumors shrank or disappeared (overall response rate) was 40% with zipalertinib. For patients who had prior amivantamab, the overall response rate was 30%, but that number dropped to 14% in people who had been treated with other types of EGFR exon20 targeted treatments. Researchers hypothesize this drop in effectiveness could be due to drug resistance from previous treatments.
Because brain metastasis is an important concern for this patient population, the researchers also studied effects on the CNS and found zipalertinib had good activity and penetration in the brain. With additional studies underway, these results suggest zipalertinib is a promising option for patients with brain metastasis.
KRAS
Just a few years ago, metastatic KRAS+ NSCLC was considered “undruggable,” and now we have immunotherapy and two KRAS G12C-targeted therapies—adagrasib and sotorasib—for this patient population. Researchers continue to build on these tremendous advances in treating patients with KRAS+ NSCLC.
To bolster the benefits of existing KRAS-directed drugs for newly diagnosed patients, researchers studied the effectiveness of using adagrasib combined with pembolizumab to treat patients with previously untreated advanced KRAS G12C+ NSCLC in a phase 2 study. The data showed a 44% overall response rate and 26.3 months as the median duration of response (length of time the treatment stops the cancer from growing or spreading) for patients with all levels of PD-L1 expression. This promising approach is already being expanded into two global phase 3 trials (KRYSTAL-7 and KRYSTAL-4) that are currently enrolling patients.
A second-generation KRAS-directed drug, olomorasib, was also studied in combination with pembrolizumab to improve outcomes for newly diagnosed patients with advanced KRAS G12C+ NSCLC, with very promising results. The overall response rate for patients treated with the combination was 70% across all levels of PD-L1 expression, and 90% of patients benefited from treatment (disease control rate). The research is continuing in SUNRAY-01, a global phase 3 study that is currently enrolling patients.
As researchers learn more about mutations that drive the development and growth of cancer such as KRAS G12C, they have also made progress learning about important co-mutations that occur in tumor suppressor genes such as STK11, TP53, and others.
Researchers presented data on the impact of co-mutations on the effectiveness of sotorasib on KRAS G12C+ NSCLC. The data revealed the group of patients whose tumors had both KRAS G12C and TP53 mutations responded as expected to sotorasib, while those with STK11 co-mutations had a significantly reduced response. This trial requires additional validation, yet it demonstrates the importance of understanding which co-mutations are present. Researchers will continue to study the impact of co-mutations on the effectiveness of targeted therapy.
HER2
Promising data is emerging for 2 HER2-directed TKIs—sevabertinib and zongertinib. Both drugs are being tested in previously untreated patients and have been granted Breakthrough Therapy designation and Priority Review by the FDA. If tests continue to go as expected, we’re likely to have one or both of them available in the near future.
Thanks for Joining Us!
A wide range of lung cancer studies were presented at the annual ASCO conference as researchers conduct studies to improve outcomes for people with lung cancer in the US and around the world. Working together, we are transforming what it means to be diagnosed with lung cancer.
LUNGevity brings you scientific highlights from major lung cancer conferences throughout the year. If you missed our coverage of the American Association for Cancer Research (AACR), you can read it here.
Join us again for our coverage of the World Lung Cancer Congress in Barcelona Sept. 6-9, 2025.
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