A total of 771 questionnaires were collected in this survey, 588 of which were identified as containing valid answerers provided by clinicians after filtration. Thus, the valid response rate of the current status survey was 76.3%.
1. General information
The survey was an investigation of a large number of doctors of various professional qualifications nationwide from different types and cancer treatment-related departments of hospitals in thirty provinces and autonomous regions of China.
According to statistical analysis, we sorted the amount of the questioned doctors from different locations in decreasing order as follows: Shandong Province (105, 17.8%), Hebei Province (86, 14.6%), Guangdong Province (70, 12.0%), Henan Province (48, 8.2%) and Jiangsu Province (37, 6.3%).
Among the surveyed doctors, 588 were divided into 6 categories based on their professional qualifications. There were 82 chief physicians (13.9%), 153 associate chief physicians (26.0%), 159 physician-in-charge-level physicians for more than three years (27.0%), 71 physician-in-charge-level physicians for less than three years (12.1%), 106 resident physicians (18.0%) and 17 physicians with other qualifications (2.9%).
The responding doctors came from different types of hospitals that varied in hospital levels, consisting of five levels: 341 doctors came from grade III level A hospitals (58.0%), 59 came from grade III level B hospitals (10.0%), 106 came from grade II level A hospitals (18.0%), 76 came from cancer hospital (12.9%), and 6 came from other institutions (1.0%).
We also surveyed the responding physicians’ distribution across a diverse range of cancer treatment departments within the hospitals, including 365 doctors from medical oncology departments (62.1%), 64 from tumor-related surgical departments (10.9%), 65 from hematology departments (11.0%), 41 from radiotherapy departments (7.0%), 18 from chemoradiotherapy departments (3.1%) and 35 from other departments (6.0%).
2. Status of the application of PD-1/PD-L1 inhibitors in the clinic
Prescription
According to the survey, less than one-third (158, 26.9%) of respondents participated in clinical trials, while the rest (430, 73.1%) did not, but 348 of the 588 respondents, approximately 59.2% of the doctors surveyed, had prescribed PD-1/PD-L1 inhibitors during clinical treatment. The 240 doctors who did not prescribe PD-1/PD-L1 inhibitors were asked to choose from several reasons listed for why they had not prescribed these inhibitors, which suggested three major reasons, including 126 responses for “do not understand the mechanism and the efficacy of the drug”, 115 responses for “no purchasing options” and 113 responses for “the expensive price”. The results are presented in Fig. 1. The number of responses for each option was calculated and the results are displayed in order from highest number of responses to lowest number of responses. The most common reasons are highlighted in yellow. When the doctors were asked the question “Would you choose the imported (eg. nivolumab and pembrolizumab) or domestic drugs (such as toripalimab, sintilimab, and camrelizumab) in China as the preferred alternative?”, 44.8% of them answered “unbias”, 35.1% and 20.1% of the doctors said that they would select imported or domestic drugs firstly, respectively.
Indication for medication
In this survey, PD-1/PD-L1 inhibitors were shown to have been applied in many tumor types, and their application in lung cancer far exceeded that in other tumor types. The order of application for PD-1/PD-L1 inhibitors in different cancer types ranging from highest use to lowest use is as follows: lung cancer, liver cancer, melanoma, colorectal cancer, lymphoma, gastric cancer, esophageal cancer, renal cancer, and breast cancer. The survey showed that 271 (77.9%) of the 348 prescribers used the inhibitors in an off-label situation, and of these, 115 physicians (33.0%) indicated that they used the inhibitors in off-label situation in “1-9% of cases”, 83 physicians (23.9%) indicated that they used the inhibitors in off-label situations in “10-20% of cases”, 45 physicians (12.9%) indicated that they used the inhibitors in off-label situations in “30-50% of cases”, and 28 physicians (8.0%) indicated that they used the inhibitors in off-label situations in “over 50% of cases”.
The motivation for off-label medication was surveyed in the questionnaire, and the 271 “experienced” doctors were asked to choose their motivation. The most important motivation was that “there are indications abroad but not domestically”, which was chosen by 173 doctors (63.8%) of 271. Additionally, the criteria for carrying out off-label medication were surveyed as well. Most doctors (200 of 271, 73.8%) agreed that there had to be both advanced evidence and overseas indications. The detailed results of the motivation survey are presented in Fig. 2. The proportion of prescribers for each option was calculated, and the most important motivation is marked in yellow. In Fig. 3, the detailed results of the criteria survey are shown; the prescribers used off-label medication based on diverse criteria, and the most common criterion is highlighted in yellow.
Personal countermeasures when the therapy was found ineffective
Although some respondents did not prescribe PD-1/PD-L1 inhibitors, all 588 physicians were required to answer this question. They had to choose a countermeasure when the efficacy of the drug was not observed at an early stage of immunotherapy, and the majority (259 doctors, 44.0%) of them indicated that they would consider a combination with other drugs. The details of the personal countermeasures survey are displayed in Fig. 4, which shows that most respondents would consider continuing the ongoing PD-1/PD-L1 inhibitor therapy in several ways. In addition, when asked whether they would change to another PD-1/PD-L1 inhibitor if such an event occurred, 66.0% of 588 respondents chose “No”, and the remaining 34.0% chose “Yes”.
Prescribing physician’s knowledge of drug safety
The 348 prescribing physicians ultimately shared a clear and general consensus on the indications for withdrawal of PD-1/PD-L1 checkpoint inhibitors, with the survey indicating that the drug needed to be discontinued when grade III and above adverse effects (257, 73.9%) or hyperprogression (223, 64.1%) occurred. Most doctors (264 of 348, 75.9%) held the perspective that immunotherapy-related adverse effects could be controlled or managed through follow-up management. In contrast, a few doctors (17, 4.9%) claimed that the drug should be applied cautiously due to the occasional occurrence of serious adverse effects. Additionally, some doctors (66, 19.0%) believed that training about adverse effects of treatment should be strengthened.
3. Oncologists’ concerns regarding utilization
When the 348 prescribing physicians were asked “Is it necessary to detect the gene expression level of PD-L1 before PD-1/PD-L1 inhibitor therapy?”, 212 (60.9%) chose “Yes”, 21 (6.0%) chose “No”, 97 (27.9%) chose “Judge according to drug indications”, 14 (4.0%) chose “Not sure”, and 3 (0.9%) chose “Other”. However, when they were asked, “Is it necessary for patients to do the large-panel gene detection before PD-1/PD-L1 inhibitor therapy?”, 118 (33.9%) chose “Yes”, 111 (31.9%) chose “It depends, and I know clearly whether a patient needs it or not”, 76 (21.8%) chose “It depends, but I am not very sure whether a patient needs it or not”, 38 (10.9%) chose “Generally, no”, and 4 (1.1%) chose “I do not know”.
What the 348 doctors using the PD-1/PD-L1 inhibitors were most concerned about was also included in the questionnaire. The results showed four groups of answers, including two identical groups (both included 111 of 348, 32%) of doctors who were most concerned about “how to identify pseudoprogression and hyperprogression” and “immunity-related adverse effect management”, 66 doctors (19.0%) who were concerned about “how to further improve the efficacy of the drug”, and 59 doctors (17.0%) who were concerned about “resistance mechanism and selection of follow-up treatment”.