Editor’s Note: The 2024 CSCO Guideline Conference, co-hosted by the Chinese Society of Clinical Oncology (CSCO) and the Beijing Hope Science Clinical Oncology Research Foundation, took place in Jinan on April 26-27. At the event, Professor Jun Guo from Peking University Cancer Hospital was interviewed by “Oncology Frontier.” He discussed significant updates in the new editions of the CSCO guidelines for urothelial carcinoma and melanoma, shared insights into the unique features of the CSCO guidelines, and provided an overview of the current and future states of anti-cancer drug development in China.
Oncology Frontier: In recent years, new ADC drugs have emerged in the field of urothelial carcinoma. Could you discuss the impact of ADCs on the clinical practice for this type of cancer?
Professor Jun Guo: Esteemed colleagues, today at our CSCO Guideline Conference, we announced some important updates to the urothelial carcinoma guidelines. Among all the CSCO guidelines released, those for urothelial carcinoma have seen significant changes. This is primarily due to a major shift in first-line treatments, which has subsequently led to substantial changes in second-line and adjuvant therapies. For example, the results of the EV-302 study were groundbreaking, showing that the combination of Enfortumab Vedotin (EV) and pembrolizumab significantly outperformed chemotherapy.
For the past two to three decades, chemotherapy has dominated as the first-line treatment for urothelial carcinoma. Despite numerous clinical studies combining chemotherapy with PD-1 inhibitors, all except the Checkmate-901 study have failed to make an impact. This means chemotherapy’s status as the standard first-line treatment remained unshaken. However, recent results from the EV-302 study demonstrated that the combination of Enfortumab Vedotin and pembrolizumab has completely defeated chemotherapy. Moreover, a recent clinical study led by China showing the combination of RC48 and a PD-1 inhibitor promises to surpass chemotherapy, with very encouraging preliminary results.
Thus, the guidelines for urothelial carcinoma have undergone a complete overhaul in this update. Now, either EV or RC48 combined with a PD-1 inhibitor has become the new standard for first-line treatment of urothelial carcinoma, pushing chemotherapy to a second-line role. Additionally, ADC treatments have become the most prominent and significant recommendations for various conditions within urothelial carcinoma. Indeed, the changes in the CSCO guidelines for treating urothelial carcinoma are substantial.
Oncology Frontier: You are also an authority in the field of melanoma, spearheading the establishment of a standardized diagnostic and treatment system for melanoma in China. How should melanoma be identified early, and how can the treatment be further standardized?
Professor Jun Guo: The melanoma sector has also seen significant changes in the CSCO guidelines. There are substantial differences between the situation of melanoma in China and that in the West, particularly since over half of the melanomas in Chinese patients are acral melanomas. Historically, the standard treatment for these melanomas has been chemotherapy or single-agent PD-1/PD-L1 inhibitors. All PD-1/PD-L1 inhibitors approved in China have been for second-line treatment after chemotherapy failure.
However, this year’s guidelines have been significantly updated. We have now included a triple-drug combination—temozolomide, apatinib, and a PD-1 inhibitor—as a first-line treatment option for acral melanoma. This change was due to the breakthrough results achieved with this triple-drug combination, which raised the effective rate to 60-70%, compared to 5% with chemotherapy and 13% with PD-1 inhibitors. Based on this breakthrough, we have made significant adjustments to the first-line treatment recommendations for acral melanoma. Additionally, for mucosal melanoma, we now recommend a targeted-immunotherapy combination of axitinib and a PD-1 inhibitor, replacing the previous treatments of chemotherapy alone or a single-agent PD-1 inhibitor. These are some of the more significant changes in the new edition of the CSCO melanoma guidelines.
Oncology Frontier: How can we better integrate China’s unique characteristics and clinical practices to develop guidelines more suited to Chinese patients?
Professor Jun Guo: The major difference between the CSCO and NCCN guidelines is our focus on integrating local disease characteristics, particularly for Asian cancer patients and clinical research led by Chinese experts. There are two main reasons for this approach. First, the Chinese cancer patient population has unique characteristics, such as a higher proportion of EGFR mutations in lung cancer and subtypes like acral and mucosal in melanoma. These characteristics necessitate treatment approaches that may differ from those in the West. Second, we conduct targeted clinical research based on these characteristics and have obtained various levels of evidence-based medical evidence. Based on this evidence, we make recommendations that also consider accessibility and affordability.
Therefore, the CSCO guidelines are likely more applicable to Chinese doctors and patients, offering more personalized and targeted treatment decisions. I believe that the CSCO guidelines are currently the most practical and relevant clinical diagnostic and treatment guidelines in the Chinese clinical oncology community.
Oncology Frontier: China’s innovative drugs are continually advancing. Could you share your expectations or suggestions for the future development of China’s innovative drug research and development?
Professor Jun Guo: In recent years, China’s development of clinical oncology drugs has entered a golden age. This includes a large number of immune therapy drugs represented by PD-1/PD-L1 inhibitors, ADC drugs, and future cell therapies expected to play a significant role in cancer treatment, such as TIL therapy, CAR-T therapy, and TCR therapy. Additionally, new radionuclide treatments guided by biological markers are rapidly developing in China. I firmly believe that Chinese pharmaceutical companies can capitalize on this momentum to further expand and enhance the development of new anti-cancer drugs in China. Indeed, we have already achieved greater success now than in the past two to three decades.
Looking ahead, I am confident that Chinese pharmaceutical companies will continue to excel, providing more drugs for clinical trials to our clinical oncologists. Through clinical research by Chinese oncologists, more beneficial anti-cancer drugs will be rapidly approved and ultimately benefit Chinese cancer patients. I firmly believe that this is a common aspiration among all pharmaceutical companies, professionals involved in cancer treatment, and patients, and this day will surely come soon.
