ASCO GU 2021: The immunotherapy of prostate cancer has dawned

In recent years, immuno-checkpoint inhibitors represented by PD-1/PD-L1 monoantigen have been breakthrough in several tumors, including melanoma, lymphoma, NSCLC, liver cancer, breast cancer, etc.
but in advanced prostate cancer, it's relatively late to explore.
, K-drugs can be treated with K-drugs in people with "universal adaptation", i.e. microsatellite instability and high mutation loads of tumors.
, however, there is no direct evidence for the overall prostate cancer population.
previous studies for new endocrine therapist treatments and individual immunotherapy after chemotherapy failures have not been successful.
as a result, the forward shift of PD-1/PD-L1 monoantigen therapy and the combination with existing treatments have become the focus of clinical research on advanced prostate immunotherapy, and are the highlights of the 2021 ASCO GU Conference in the past untreated mCR The CheckMate 9KD study CheckMate 9KD (NCT03338790) study of Narvulyu monoantigen in PC patients was a Phase 2 clinical study of the treatment of mcCRPC in the Navuliyu monoantigen.
the study divided the patient into three treatment groups, A, B and C, according to the patient's past therapeutic status, and received the treatment of The Navuliyu monoantigen joint rucaparib, Navuliyu monoantigen joint dositamine and strong pine, Navuliyu single anti-combined Nzaluamine program.
this meeting reported the results of CheckMate 9KD's Group B treatment. Group
B included patients with metastatic desopathic prostate cancer (mCRPC) who had not received chemotherapy in the past, but allowed patients to receive up to two new endocrine treatments (NAT: e.g. abitron, Nzarusamine, etc.). Group
B treatment options are as follows: Navuliyu monoantigen 360mg Q3w and dossytha 75mg/m 2 Q3w plus strong pine 5mg Bid, where chemotherapy does not exceed 10 cycles, Sequential Navuliyu monoantigen 480mg Q4w maintenance therapy, until the progress of the disease (PD) or insulable side effects (up to 2 years of treatment).
the main study endpoints were objective mitigation rate (ORR) and PSA mitigation rate (defined as a decrease of ≥50% compared to baseline PSA after treatment), and secondary study endpoints were imaging progression-free lifetime (rPFS), total lifetime (OS), and safety.
study, CheckMate 9KD Study Group B, included 84 patients with a medium age of 71 years (range: 53-88 years), of whom 27% had visceral metastasis and 54% (45 cases) had measurable lesions.
the number of meso-cycles of chemotherapy in dossin is 8 cycles, and the number of mid-doses of Navuliyu monoantigen is 11.
results are summarized as follows: PSA remission rates were significantly higher and the medium rPFS time was longer in patients who had not received NAT in the past.
OS data is immature, as can be seen from the OS curve, the two sets of OS curves that accept or have not received NAT begin to cross in about 1 year, and the OS curve that has not received NAT groups has maintained an absolute advantage since then.
, therefore, in general, Navuliyu monoantigen Dorsey chemotherapy in previously unmotive mCRPC patients with significant efficacy, safety and reliability.
(2) THE KEYNOTE-365 study of Pablo Pearl monoantitor was a phase 1b/2 clinical study of mCRPC patients who had not previously been treated with chemotherapy but had been treated with abitron or ntazalumide, divided into A, B, C, D four combined treatment groups, respectively, received Paboliju monoantigen joint Olapali, Paboliju monoantigen combined dositan and strong pine, Paboli pearl monoantigen combined ozalum, Paboliju single anti-combined abitor and strong pine program treatment.
this research design is very similar to the CheckMate 9KD study.
the results of group B treatment updates for KEYNOTE-365 were reported at this ASCO GU conference.
Group B treatment options are: Pabli pearl single resistance 200mg Q3w s dodosi race 75mg/m 2 Q3w s strong pine 5mg Bid until PD.
main study endpoints were: Safety, ORR, and PSA mitigation rates (defined as a decrease of ≥50% compared to baseline PSA after treatment), and secondary study endpoints were Disease Control Rate (DCR), rPFS, and OS.
study included 104 patients with a medium age of 68 years (range: 50-86 years), of whom 25.0% had visceral metastasis and 50.0% (51) had measurable lesions and 103 PSA patients could be evaluated.
overall ORR was 23.1%, DCR was 76.0% and PSA mitigation was 34.0%.
the current mid-level follow-up time is 32.4 months, the middle rPFS is 8.5 months (8.3 months -10.1 months), and the middle OS is 20.2 months (16.9 months-24.2 months).
96.2 per cent of adverse events (TRAEs), including diarrhoea (41.3 per cent), fatigue (41.3 per cent) and hair loss (40.4 per cent).
≥ TRAEs at level 3 were 44.2%, with the feberative neutral granulocytes dropping to 11.5%.
32.7% of adverse events (irAEs) associated with immunotherapy and 8.7% ≥ of level 3 iraAEs.
2 treatment-related deaths, all of which were pneumonia.
new endocrine drug administration has become the main treatment option for the potential-resistant prostate cancer, and there is no standard treatment for the follow-up treatment of these patients.
Because the KEYNOTE-365 study group B and CheckMate 9KD study group B (previous NAT) were all patients with mcCRPC who had not previously had chemotherapy, the study was also immuno-combined dositan and strong pine chemotherapy, which allowed for a rough lateral comparison.
For mCRPC patients who had not previously been treated with chemotherapy but had received new endocrine therapy, the ORR of the two immuno combination chemotherapy studies varied slightly, while the PSA remission rate, rPFS, and OS were all comparable, and the side reactions were similar and controllable.
Phase 3 clinical studies consistent with CheckMate 9KD's Group B study design (CheckMate 7DX, NCT04100018) and Phase 3 clinical studies consistent with KeyNOTE-365's Group B study design (KEYNOTE-921, NCT03834506) are currently in an orderly manner.
based on their excellent Phase 2 study data, the results of these phase 3 studies are very worth looking forward to.
immunotherapy, still to be explored (1) Pablic pearl monoantigen irradiation treatment, not expected radon 223 as early as 2013 has been approved by the U.S. FDA for bone metastasis mCRPC patients treatment, and in 2020 was approved in China the relevant adaptation certificate.
has been suggested in previous studies that radon 223 may increase immunogenicity in patients with mCRPC bone metastasis and thus increase the anti-tumor activity of immunosuperative inhibitors (ICI).
the ASCO GU Conference, a Phase 2 clinical study of the treatment of Pabliju monoantigen 223 was reported.
the study was 2cm mCRPC patients with bone metastasis>, no visceral metastasis, or lymph node metastasis.
patients were randomly assigned to the 223 55kBq/kg Q4w and Pablo Pearl Single Resistance 200mg Q3w Treatment Group (Group A) or the X223 55kBq/kg Q4w Single Drug Treatment Group (Group B).
After 3 treatments of radon 223, if the evaluation effect is at least stable (SD), then group A patients deactivate radon 223, using Pablic pearl monoantigen resistance to maintain to PD, and PD, as long as there is no internal organ transfer, will resume radon 223 treatment until PD or insulable toxicity or complete a total of 6 treatment of radon 223.
of the 45 patients in the group, 42 patients were assessed for efficacy (29 cases in Group A and 13 cases in Group B).
10% of level 3 non-hematological TRAEs in Group A and no level 3 non-hematological TRAEs occurred in Group B.
rPFS in the two groups were 6.7 months (95% CI: 2.7 months - 11.0 months) and 5.7 months (95% CI: 2.6 months) respectively -Not reached); the mid-OS was 16.9 months (95% CI: 12.7 months - not reached) and 16.0 months (95% CI: 9.0 months - not reached), respectively.
PSA remission rates were 10% and 0, respectively, and the risk of symptomatic bone adverse events (SSEs) was 38% and 54%, respectively, and the risk of pathological fractures was 0 and 23%, respectively.
, it can be seen that the PSA remission rate, rPFS, and OS efficacy data of the two groups did not differ significantly, except for the lower risk of osteopathic events and pathological fractures in the combined group.
, immunotherapy was added to the treatment of radon 223, and although the side effect was controllable, it did not lead to an improvement in efficacy.
the results, the study also tested patient baseline and T-cell immersion of CD4 plus and CD8 plus 8 weeks after treatment with biopsy specimens, and found no difference before or after treatment.
(2) avelumab combined external radiation therapy, the disease was sustained controlled radiotherapy was considered to have synergies with ICI therapy in multiple tumor species 1,2. the
ICEPAC study is a multi-center single-arm Phase 2 clinical study that combines the PD-L1 inhibitor avelumab with stereotactic radiotherapy (SABR) to treat mCRPC patients who have previously received ≥ new endocrine treatments, allowing patients who have previously received yew chemotherapy (no more than two options) to be admitted to the group.
specific treatment options are: avelumab 10mg/kg Q2w, treatment for a total of 12 cycles (for patients who still maintain disease control after 12 cycles of treatment is allowed to continue avelumab treatment);
the study involved 31 patients, 30 of whom were assessed for efficacy.
The middle age of all patients was 71 years (four-point range: 64-75 years), only bone metastasis accounted for 42%, visceral metastasis accounted for 16%, past yew chemotherapy accounted for 84%, and past Abithlon and Nzaluamine failed 13%.
Avelumab as a second-line, third-line, fourth-line or above treatment rate of 29%, 42% and 29%, respectively.
a total of 70 metastasis lesions received SABR treatment, of which bone metastasis lesions accounted for 90% and soft tissue lesions accounted for 29%.
Avelumab treatment had a medium cycle of 9 cycles (four-part pitch: 5 cycles -13 cycles) and 41% of patients received avelumab treatment for more than 12 cycles.
≥ 16% of class 3 TRAEs.
the final DCR is 50% (95% CI: 31%-69%), the DCR for soft tissue lesions is 60% (31%-84%), and the ORR is 33% (95% CI: 12%-61%), ORR for lesions other than radiotherapy is 36% (95% CI: 11%-69%), and PSA remission rate is 23% (95% CI: 10%-42%).
18 months after the mid-level follow-up, the mid-level rPFS was 8.4 months (95% CI: 4.5 months - not reached) and the mid-OS was 17.9 months (13.1-not reached).
in mCRPC patients who had underwent multi-line therapy that had failed chemotherapy in the past (71% of patients had ≥ 3-line therapy), avelumab combined radiotherapy also resulted in relatively long-lasting disease control (rPFS s 8.4 months).
the subsequent expansion of the sample size is worth continuing.
the same time, it may be more instructive to refer to the above-mentioned immunoglomeration studies, if avelumab combined external irradiation therapy can also be combined with immuno-microencientyn background or related biomarker to predict efficacy.
Immunotherapy Efficacy Prediction Study is also struggling to explore this year's ASCO GU immunotherapy efficacy prediction studies involving prostate cancer very few studies, more research on biomarkers also focused on prognossis of prostate cancer analysis, gene spectromet analysis, DNA damage isogenous recombination repair (H H) RR) genes (BRCA1, BRCA2, ATM, PALB2, FANCA, RAD51D, CHEK2 and CDK12, etc.) and HRR gene defects (HRD) predict the efficacy of PARP inhibitors.
a study from the UK detected PD-L1 expression and gene expression spectrum (GE) in tumor biopsy specimens in mCRPC patients using all-exoscens sequencing (WES), second generation sequencing (NGS), RNA sequencing (RNAseq), immunogroupization, etc. P) score, misalmed repair (MMR) genes, and expression levels or mutations in BRCA2, PALB2, CDK12, PTEN, ATM, TP53, SOX2, etc., and associate them with the prognostication after anti-PD-1 treatment.
the study examined 100 fresh biopsy samples of tumors in mCRPC patients.
the medium follow-up of 56.2 months, in all test samples, SOX2 positive expression rate was found to be 27%, PD-L1 positive expression rate of 33%, GEP high-scoring patients 26%, and PD-L1 expression and GEP score positive correlation.
addition, mmR pathological mutation rate was 7%, BRCA2 gene harmful mutation rate was 9%, PALB2 mutation rate was 1%, CDK12 mutation rate was 3%, PTEN and ATM expression loss were 29% and 13%, respectively, and TP53 mutation rate was 25%.
single-factor analysis shows that PD-L1 positive expression (HR s 1.75,95%