Editor's Note: Modern advancements in oncology have introduced various breakthrough treatment options for lung cancer, which is now one of the most rapidly evolving solid tumors. To help clinicians stay updated on key advancements in this field, Oncology Frontier has partnered with Dr. Hua Zhong and Dr. Baohui Han of the Department of Respiratory and Critical Care Medicine at Shanghai Chest Hospital to launch the Zhōng & Huì Insights clinical progress series. Through in-depth analyses of high-quality clinical research in lung cancer, the series aims to elevate clinical practice standards. In this 24th installment, the professors discuss the results of the study titled "Efficacy and Safety of Docetaxel Combined with Plinabulin in Second-Line Treatment for Mutation-Negative Advanced NSCLC Patients," published in The Lancet Respiratory Medicine by Dr. Baohui Han as the first author.

Study Overview: Docetaxel Combined with Plinabulin vs. Docetaxel Alone in Second-Line Treatment of NSCLC

Dr. Baohui Han：For patients with mutation-negative advanced NSCLC, immunotherapy combined with platinum-based chemotherapy is the standard first-line treatment. However, once disease progression occurs, effective treatment options are limited, representing an urgent clinical need. Docetaxel is the most widely used standard treatment strategy, yet its efficacy remains limited, with an overall PFS of only around three months and an ORR of just 10-15%. Numerous new treatment strategies have been explored and analyzed, but many have failed.

For instance, the CONTACT-01 study explored the comparison between atezolizumab combined with cabozantinib and docetaxel. The results showed that the median OS in both groups was 10.7 months and 10.5 months, respectively, with a hazard ratio (HR) of 0.88 and a p-value of 0.3668. The 1-year OS rates were 43.3% and 44.1%, respectively. The median PFS was 4.6 months and 4.0 months, respectively, with an HR of 0.74. The 6-month PFS rates were 39.5% and 23.7%, and the 1-year PFS rates were 14.7% and 8.4%. The objective response rates (ORR) were 11.8% and 13.3%, respectively. Similarly, the SAPPHIRE study explored nivolumab combined with sitravatinib, which also failed to show superiority over docetaxel monotherapy. Other combinations, including docetaxel with S1 or immune checkpoint inhibitors targeting TIGIT or TROP-2, have yielded unsatisfactory results. In this study, 74 patients in the monotherapy group and 77 patients in the combination therapy group were included in the analysis. The median PFS for the two groups was 3.5 months and 4.1 months, respectively, with a hazard ratio (HR) of 0.823. The median OS was 9.8 months and 12.3 months, respectively, with an HR of 0.984, and the 1-year OS rates were 43.5% and 52.6%. The objective response rates (ORR) for the two groups were 9.5% and 17.1%, respectively, with no statistically significant differences. Additionally, dual immune therapy strategies such as PD-1 combined with TIGIT and antibody-drug conjugate (ADC) treatment strategies targeting TROP-2 have been explored, but the data were not satisfactory.

Plinabulin is an immune modulator that promotes dendritic cell maturation and T cell activation. This study showed that combining plinabulin with standard docetaxel treatment offered a certain degree of benefit to patients. However, it is important to note that this data only moderately improved patient outcomes, and further collaborative efforts are needed to find better treatment strategies for this patient population.

Dr. Hua Zhong：”Resistance” remains a major challenge in lung cancer treatment. Regardless of whether the treatment involves targeted therapy or immunotherapy, a substantial portion of patients experience disease progression due to resistance, ultimately leading to treatment failure. Identifying the mechanisms of resistance is critical for the development of new drugs and personalized treatment approaches. In targeted therapy, re-biopsying after resistance and providing targeted therapies based on different resistance mechanisms has improved efficacy and safety.

Unfortunately, the mechanisms of immune resistance are not yet well understood, leading to a lack of precision treatments based on resistance mechanisms. Docetaxel remains a widely used clinical treatment but offers limited efficacy, with an overall PFS of only three to four months and noticeable side effects, particularly gastrointestinal and hematologic reactions. Previous combination strategies—including docetaxel with canakinumab, S1, dual immunotherapy, ADCs, or anti-angiogenic agents—have all been disappointing.

This Phase III clinical trial found that adding plinabulin to docetaxel improved patient survival, achieving a rare positive result. Moving forward, it will be interesting to see whether novel treatments such as cellular therapy or targeted protein degradation can be applied in this field.

Dr. Baohui Han

• Honorary Director, Department of Respiratory Medicine, Shanghai Chest Hospital
• Accomplished leader in respiratory medicine
• Recipient of multiple national and regional awards
• Executive member of multiple national and international cancer committees, including CSCO

Prof. Zhong Hua

• Director of Respiratory Medicine, Shanghai Chest Hospital
• Specialized in lung cancer immunotherapy research
• Holds leadership positions in several medical societies, including the Chinese Society of Clinical Oncology (CSCO)