Editor’s Note: The 2024 Academic Conference on Precision Diagnosis and Treatment of Lung Cancer recently featured a presentation by Dr. Yan Huang from the Sun Yat-sen University Cancer Center, titled Advances in Perioperative Drug Therapy for NSCLC in 2024. In an interview with Oncology Frontier, Professor Huang elaborated on the key topics in this rapidly evolving field.Oncology Frontier: Perioperative treatment for early-stage non-small cell lung cancer (NSCLC) has entered the era of targeted and immunotherapy. What breakthroughs in perioperative targeted therapy were seen in 2024?
Dr. Yan Huang: With advancements in lung cancer screening technologies and increasing public awareness of health checkups, more cases of early-stage lung cancer have been detected in recent years. For stage II–III NSCLC, surgery alone is often insufficient, and many treatment options now exist to consolidate surgical outcomes. In the realm of perioperative targeted therapy, the most significant breakthroughs in recent years have occurred in the adjuvant setting, with some smaller studies emerging in neoadjuvant therapy in 2024.
In terms of adjuvant targeted therapy, major progress has been driven by results from the ADAURA and ALINA studies published in recent years. The phase III ADAURA trial demonstrated that adjuvant osimertinib, a third-generation EGFR-TKI, significantly delays postoperative recurrence in NSCLC patients with EGFR exon 19 deletions or L858R mutations. Five-year follow-up data released in 2023 confirmed that three years of postoperative osimertinib markedly improves overall survival (OS). For ALK-positive NSCLC, the ALINA study’s preliminary results, presented at the 2023 ESMO conference, showed that adjuvant ALK inhibitor therapy following surgery significantly improved disease-free survival (DFS) compared to traditional chemotherapy, reducing the risk of recurrence.
Additionally, research is ongoing to evaluate whether targeted therapies for rare mutations can be moved earlier into the perioperative setting. However, given the small number of patients with rare targets, large-scale perioperative trials remain challenging. Collaborative efforts and data sharing will be essential to advance this field.
Oncology Frontier: What significant progress was made in perioperative immunotherapy for driver-negative NSCLC over the past year?
Dr. Yan Huang: Perioperative immunotherapy has advanced significantly in recent years, and 2024 brought substantial new data, including updates from long-term follow-ups of large clinical trials.
The first positive results came from the phase III CheckMate-816 trial, which evaluated neoadjuvant immunotherapy. This was followed by results from adjuvant immunotherapy trials such as IMpower010 and KEYNOTE-091, and perioperative trials like AEGEAN. Among this year’s most important findings were those from perioperative “sandwich” immunotherapy trials. The second interim analysis of the KEYNOTE-671 study, recently published in The Lancet, showed that perioperative pembrolizumab combined with chemotherapy significantly improved the 3-year OS rate compared to traditional perioperative chemotherapy. These findings led to approval of the regimen in China. International trials, including KEYNOTE-671, AEGEAN, and CheckMate-77T, along with domestic studies like Neotorch and RATIONALE-315, have demonstrated the potential advantages of the “neoadjuvant + adjuvant” immunotherapy model.
Post-hoc and subgroup analyses from KEYNOTE-671 have provided valuable insights for perioperative immunotherapy. A post-hoc analysis presented at the 2024 WCLC revealed that the neoadjuvant chemo-immunotherapy group achieved deeper pathological responses, as indicated by the percentage of residual viable tumor (%RVT). Over the next few years, more details from these large clinical trials are expected, which will further validate perioperative immunotherapy and establish new standards of care.
Oncology Frontier: Perioperative treatment for NSCLC still faces challenges and controversies, such as the choice between neoadjuvant immunotherapy, adjuvant immunotherapy, or the “sandwich” model of neoadjuvant + adjuvant immunotherapy. How can clinicians choose the most appropriate treatment for individual patients? Could you share your insights?
Dr. Yan Huang: There are three main types of perioperative immunotherapy:
- Neoadjuvant immunotherapy, which combines chemotherapy with immunotherapy before surgery.
- Adjuvant immunotherapy, which consolidates treatment after surgery.
- The “sandwich” approach, involving neoadjuvant chemo-immunotherapy followed by postoperative adjuvant immunotherapy.
Which approach is superior, and how should early-stage driver-negative NSCLC patients choose the most suitable model? These remain open questions, as the current evidence is still evolving.
In general, many clinicians favor the “sandwich” approach, as it covers the entire treatment course and may improve survival outcomes. However, this model is not suitable for all patients. In my experience, the primary advantage of neoadjuvant chemo-immunotherapy lies in tumor downstaging, making initially unresectable tumors operable. For patients who are good candidates for surgery without requiring downstaging, or those who cannot tolerate neoadjuvant chemo-immunotherapy due to physical condition or other reasons, postoperative adjuvant immunotherapy becomes more critical.
A data analysis presented at the 2024 WCLC compared perioperative and neoadjuvant immunotherapy using patient-level data from the CheckMate-77T and CheckMate-816 trials. These findings further support the use of perioperative nivolumab as a treatment option for resectable NSCLC.
Future research should focus on head-to-head trials comparing the three models of perioperative immunotherapy to evaluate the relative benefits of the neoadjuvant and adjuvant phases. Accumulating more evidence will help guide clinicians in tailoring treatment strategies based on tumor characteristics and patient preferences.
Dr. Yan Huang
PhD, Doctoral Supervisor Chief Physician, Department of Medical Oncology, Sun Yat-sen University Cancer Center Vice Chair of the Cancer Rehabilitation and Palliative Care Committee, Chinese Anti-Cancer Association Standing Committee Member of the CSCO Oncology Supportive and Rehabilitation Therapy Expert Committee Standing Committee Member of the CSCO Geriatric Oncology Committee Chair of the Cancer Rehabilitation and Palliative Care Committee, Guangdong Anti-Cancer Association Vice Chair of the Chemotherapy Committee, Guangdong Anti-Cancer Association Vice Chair of the Precision Medicine Committee, Guangdong Clinical Medicine Society Vice Chair of the Lung Cancer Precision Treatment and Clinical Research Committee, Guangdong Clinical Medicine Society
