This national survey is the first to investigate the current status of PD–1/PD-L1 inhibitors in the Chinese mainland by distributing a questionnaire to physicians involved in cancer treatment. Among the clinicians who returned valid questionnaires, nearly 60% had prescribed PD–1/PD-L1 inhibitors, which indicates that Chinese clinicians are actively exploring the best role for immunotherapy in patients suffering from cancer in China.
In terms of the distribution of respondents’ location, 58.9% of them were located in eastern provinces in China. Because the economy in eastern China develops faster than that in the west, naturally, doctors from eastern provinces are more likely to communicate with the international community regarding medical topics. With respect to the professional level of the survey respondents, they were from various high-level hospitals in China. Therefore, the respondents of the survey are representative of the all doctors involved in cancer diagnosis and treatment. Additionally, the proportion of senior doctors (physician-in-charge or a more superior position for more than three years, 66.9% in total) among the clinicians participating in the survey was relatively high, so the results of the survey are representative of the overall outlook regarding immunotherapy of tumors in the Chinese mainland. However, aside from the doctors (83.1% in total) from cancer-related departments, there was a considerable proportion (11.0%) of doctors from hematology departments, which might be attributable to the numerous recent advances in immunotherapy for treatment of hematological tumors [13].
In actuality, most (59.2%) clinicians that were surveyed had already prescribed PD–1/PD-L1 inhibitors in clinical work, while only a few (26.9%) of the prescribing physicians ever taking part in ICI-related research, including clinical trials. These results can be interpreted in two ways.
On one hand, the fact that PD–1/PD-L1 inhibitors have wide application across various tumors reflects their theoretic validity, which has been recognized by an increasing number of Chinese prescribers. Considering treatment of NSCLC as an example, in just three years, immunotherapy has progressed from monotherapy to combined therapy, from second-line standard therapy for advanced tumors to first-line therapy [14] and from salvage therapy for advanced tumors to consolidation therapy for locally advanced tumors and neoadjuvant therapy for early and mid-stage tumors [15]. The rapid accumulation of evidence of the efficacy of PD–1/PD-L1 inhibitors has inspired Chinese physicians to implement them in practice. Weiss et alrecently proved that pembrolizumab could be given to metastatic pancreatic adenocarcinoma patients, and the efficacy appears to be improved compared with that of standard gemcitabine and nab-paclitaxel dosing [16]. In fact, similar combination immunotherapy has been applied as a first-line treatment for advanced pancreatic cancer in many hospitals in the Chinese mainland. In addition, increased use of the drug can stimulate medical departments to carry out ICI-related research in line with the specific characteristics of Chinese cancer patients, which probably will enable the medical staff to more precisely diagnose and cure ‘immunity-related adverse effects’, which were noted as one of the top two concerns of the prescribers on the survey. Of note, the CSCO IO Committee published Management Guideline of Immune Checkpoint Inhibitor-Related Toxicity in April 2019. This is the first local guideline focusing on immunotherapy, and using it, the prescribing physicians’ safety knowledge concerning such drugs will be enhanced, and those prescribers that called for training regarding treatment of adverse effects may transition into bold but knowledgeable medical oncologists. In addition, although inland indications for PD–1/PD-L1 inhibitors were approved later than they were abroad and there are less approved indications, most clinicians (77.9%) have prescribed the drug according to clinical research data and foreign indications. Such practical experience has the potential to make the criteria for off-label use clearer and to shed light on future directions of theoretical and clinical study. All the above findings indicate that exploring the usage of PD–1/PD-L1 inhibitors in China will undoubtedly promote the evolution of cancer immunotherapy in the country.
On the other hand, the fact that over 70% of respondents have never engaged in any ICI-related research hints that some conflicts exist that are worth discussing. The first issue appears to be the lack of understanding of the mechanisms and efficacy of PD–1/PD-L1 inhibitors, which was the most significant factor preventing some respondents from prescribing the drug. Second, there is extensive use of PD–1/PD-L1 inhibitors in off-label situations (77.9%). For instance, pembrolizumab is approved for metastatic melanoma and advanced NSCLC in China, while it is approved for classical Hodgkin lymphoma, metastatic nonsquamous NSCLC, metastatic urothelial carcinoma and metastatic gastric or gastroesophageal junction adenocarcinoma in America [17]. However, our survey suggests that actual applications of ICIs in China exceed the indications approved by the China Food and Drug Administration. Third, prescribers who have not participated in any relevant research are not qualified to “identify pseudoprogression and hyperprogression” (another one of the top two concerns regarding drug utilization); therefore, they usually have trouble judging efficacy and deciding whether to discontinue the treatment or switch to another ICI. Finally, a few prescribers (4.9%) did not accurately recognize the safety of the drug owing to the occasional occurrence of serious adverse effects, and this lack of recognition partly resulted from incomplete theoretical and clinical knowledge and applicable guidelines. The above deficiencies may not only impact the treatment and prognosis of patients with tumors but also delay the progress of one’s personal career as a medical oncologist.
To overcome such shortcomings, the relevant state department should establish an efficient permission regulation system for conducting immunotherapy and implement specific training and re-education for doctors. Pharmaceutical companies should increase their investment in clinical trials of immunotherapy and in the promotion of this work to civilians. Additionally, clinicians should consciously take steps to study the progress of theoretical and clinical research to further standardize their clinical operation regarding immunotherapy. In addition, CSCO IO, the leader and pioneer of cancer immunotherapy in China, is bound to play a larger role in helping Chinese physicians stay up to date on the newest information about ICIs by organizing city tours, publishing guidelines, holding national conferences, and sustaining cooperation with international organizations such as the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO). With the measures above, the number of prescribers will hopefully be further increased, and both the safety index during treatment and the countermeasures to adverse effects should also increase.