PD-(L)1 Drug More How to Choose?

As of 2020/12/11 PD-(L)1 drug domestic adaptation certificate rapid expansion Since 2020, PD-(L)1 drug has been harvested in China 9 approvals, in addition to K drug in esophageal squamous cancer and head and neck cancer 2 approvals, the other 7 approval by Atiliju monoanti (Roche), Kariliju monoanti (Henri), Navuli Yudhoyono (BMS), T-Reilly Pearl Monoanti (Baiji Shenzhou) sacs: October 28, T drug approved joint beva bead single anti-first-line treatment of non-excisible hepatocellular carcinoma; On April 11th, the second-line treatment of urethrial cell carcinoma was approved for Reilly's single resistance; On 13 March, O-drug was approved for treatment of advanced or relapsed stomach cancer or gastroesophageal adenocarcinoma; T drug approved combination chemotherapy first-line treatment of small cell lung cancer Since June 15, 2018 O drug in China was the first approved second-line treatment of advanced non-small cell lung cancer to open the era of tumor tumor immunotherapy, so far, there have been 8 PD-(L)1 drugs have been approved, in 30 months to harvest 20 approvals, covering local late stage (IIIa, IIIb and IIIc phase) and metastatic (phase IV) non-small cell lung cancer (squamous and non-squamous), small cell lung cancer, liver cancer, stomach cancer, esophageal cancer, melanoma, urethra cancer, Hodgkin's lymphoma, head and neck squamous cancer and many other tumors.
PD-(L)1 drug 2018-2020 in China approved the number of adaptation certificate PD-(L)1 drugs in the domestic adaptation certificate expansion rate is amazing.
By contrast, after the U.S. was first approved for non-removable or metastatic melanoma on September 4, 2014, the FDA granted 18 approvals (11 O, 5 K, 2 T) over a 30-month period (as of March 4, 2017), covering only malignant melanoma, advanced non-small cell lung cancer, urethra cells, and neck cancer.
the rapid expansion of the drug PD-(L)1 does not appear to be slowing down.
Not only K medicine, O drug, T drug in 2020 to continue to submit new tumor species, new adaptation certificate of the listing application, the development of domestic PD-(L)1 drug second-tier enterprises have also appeared: November 23, CDE formally accepted K drug first-line treatment MSI-H colorectal cancer listing application, to "meet the conditions of approval of drugs" to include the application in the priority review; On November 23, CDE accepted the application for listing of adult patients with non-excisible non-epithelial malignant thoracic mesothelioma who are not removable with O-drug combined with epithelial monotherapy, and on November 13, CDE accepted the application for the listing of non-small cell lung cancer (scale and non-scale) with "conditional approval of drugs"; CDE accepts applications for the listing of metastasis NSCLC for the first-line treatment of T-drug single-drug PD-L1-positive, EGFR/ALK-negative; CDE accepts applications for the listing of Jia and bioGeno monotherapy exotremical T-cell lymphoma; On May 28, CDE accepted the listing application of Kangfang BioPian Pulis single anti-treatment recurring or refractic classic Hodgkin's lymphoma (cHL);
In fact, the number of adaptation certificates approved for the K drug in the United States has reached 28, covering 16 different types of solid and blood tumors, as well as MSI-H/dMMR and TMB-H, two pan-tumor adaptation certificates that do not distinguish between tumor types.
O drug was also approved in the United States for 15 adaptation certificates, covering 11 tumor species.
K drug approval adaptation certificate schematic On July 8 this year, the State Drug Administration promulgated and implemented the "Breakthrough Therapeutic Drug Review Procedure (Trial)", "Drug Conditional Approval Application Review and Approval Procedure (Trial)" and "Drug Listing License Priority Review and Approval Procedure (Trial)", in which "Conditional Approval" aims to speed up the listing of clinically urgently needed drugs with outstanding clinical value.
It can be foreseen that with the deepening and promotion of China's drug review system reform, innovative drug accelerated review and approval system will continue to enrich and improve, K drugs, O drugs, T drugs and other imported PD-(L)1 drugs or can use the new drug evaluation mechanism to speed up its domestic adaptation certificate coverage, with a richer adaptation certificate "ammunition" to combat the domestic PD-1 oppressive siege.
PD-(L)1 drugs, how can I choose clinically? The 2020 Health Care Directory Update completed its expert review at the end of October this year and officially entered the pre-negotiation phase.
In addition to TheNdili monoanti, the other seven approved PD-(L)1 drugs are on the negotiating list, and if all seven drugs are successfully negotiated, the price of PD-(L)1 drugs is likely to be significantly reduced, meaning manufacturers will have to cover a wider and more depressed hospital market and compete for more patients in order to achieve "price-for-volume".
PD-(L)1 drug approved in china the number of adaptation certificates is undoubtedly to give patients more options, but if faced with the price of almost no difference between the eight PD-(L)1 drugs, I am afraid clinicians and patients in the choice of greater problems and challenges, and naturally will ask what is the right way to open PD-(L)1.
The immunotherapy, represented by the immuno-checkpoint PD-(L)1 inhibitor, has transformed the clinical treatment of tumors by restarting the body's own immune system to fight tumors, allowing some patients to survive longer and even achieve clinical cures.
K drug, O drug treatment of malignant melanoma, non-small cell lung cancer and other solid tumor long-term follow-up study data show that some patients with advanced tumors have five years or more to survive, and in this part of the "lucky" a large part of the enduring objective tumor relief (ORR).
at the European Congress of Oncology Internal Medicine (ESMO) in September this year, five-year OS follow-up data were published in the KEYNOTE-024 study of the metastasis NSCLC population of the first-line treatment PD-L1 high expression (TPS≥50%) of the single drug.
results show that K-drug alone can live nearly one-third (31.9%) of patients with advanced NSCLC who have survived less than 5% of the past five years.
five-year OS follow-up study of KEYNOTE-024, published by ESMO 2020, and at the study data lock date (June 2020), 32 of the 39 patients who completed the two-year fixed K drug treatment course survived, and 18 patients did not develop the disease without any treatment, meaning that those who had been in advanced NSCLC were close to an unlimited clinical cure.
KEYNOTE-024: The results of an analysis of patients who completed a two-year course of treatment were more important and significant in the clinical application of PD-(L)1, where the majority of patients showed complete or partial remission (PR) of the tumor during the 12-24 weeks of use of the K drug, suggesting that the objective tumor mitigation rate (the proportion of CR-PR) was a pre-condition for long-term survival.
results of the three-year OS follow-up study of Checkmate-227, which was conducted in the United States Clinical Oncology (ASCO) conference this year, showed that In 1≥1% of patients with PD-L1≥, 70% of patients in the O-drug combined with the Ipimu monotherapy group experienced complete or partial remission within 24 weeks, while only 39% of those in the chemotherapy group survived after 3 years.
the same results were obtained in the study Checkmate-017 and the OS long-term follow-up study of Checkmate-057, which was based on the second-line treatment of O-drugs.
Patients who received CR and PR at an early stage of O-drug treatment were more likely to have long-term survival (48 weeks OS rate 58%), compared to patients treated with disease stabilization (48 weeks OS rate 19%) and disease progression (48 weeks OS rate 4%).
CheckMate 017 and CheckMate 057's landmark analysis of OS rates in patients with different efficacy, and the results of long-term follow-up studies of single-drug treatment of malignant melanoma have also shown that patients with CR/PR are more likely to achieve long-term survival after a fixed two-year course of treatment.
a data analysis of 66.8 (65.0 to 70.4) months of data from the phase III clinical study KEYNOTE-006 of the K-Drug Single Drug Control Ipimu monotherapy for malignant melanoma published by ASCO in 2019. 5-year OS rate of 43%, ORR 42% (235 cases, including 170 cases of first-line treatment and 64 cases of second-line treatment).
KEYNOTE-006 five-year follow-up OS data results: 93 out of 235 people who received objective tumor remission completed 2 years of Pabliju monotherapy and still showed remission;
KeyNOTE-006 obtained CR/PR patients after 36 months of drug suspension survival rate of up to 81%, better than the SD-only population of 66.7% of these study data for the domestic PD-(L)1 drug clinical practice significance? PD-(L)1 drugs can provide long-term survival for some tumor patients, and early (12-24 weeks) use of ORR for patients is an important consideration to determine whether patients can obtain long-term survival from PD-(L)1 medication, so PD-(L)1 drugs should continue to be used.
present, at least K and O drugs in advanced lung cancer, malignant melanoma, stomach cancer, renal cell carcinoma and other tumors in China accumulated a large amount of evidence-based medical evidence.
the efficacy of short-term treatment as reflected in the imaging results of existing PD-(L)1 to determine whether a patient is suitable for PD-(L)1 drug treatment can simplify the drug decision-making process.
same time, when clinicians are faced with PD-(L)1 drugs with no significant difference in price, there may be ideas and basis for making the right choices.
And for health-care funds, the ratio of output inputs would be the highest if resources were available to patients most likely to achieve long-term survival, and this would also promote a more regulated, scientific, orderly and robust expansion of the "exploding" domestic PD-(L)1 "cosmos".
References to the U.S.A.A., Brahmer JR, et al. KEYNOTE-024 5-year OS update:First-line(1L) pembrolizumab(pembro) vs platinum-based chemotherapy(chemo) in patients(pts) with metastatic NSCLC and PD-L1 tumour proportion score (TPS) ≥50%[EB/OL]. ESMO 2020,abstract LBA51 [4]Suresh S. Ramalingam et al., Nivolumab+ipilimumabversusplatinum-doubletchemotherapyasfirst-line treatment for advanced non-small cell lung cancer: Three-year update from CheckMate 227 Part 1. 2020 ASCO Abstract 9500 [5] Gettinger S et al., Five-Year Outcomes From the Randomized, Phase 3 Trials CheckMate 017/057: Nivolumab vs Docetaxel in Previously Treated NSCLC. 2019 WCLC, Abstract OA14.04 [6] Long GV., Long-Term Survival From Pembrolizumab Retreatment: Phase 3 KEYNOTE-006 in Advanced Melanoma, 2020 ASCO, Oral Presentation.