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The 25th National Congress of Clinical Oncology and the 2022 CSCO Annual Conference were held
in Beijing, Jinan and Harbin from November 5 to 12 in the form of a combination of offline and online.
The theme of this year's conference is precision innovation, wisdom and humanities, and we will join hands with experts and scholars in various oncology fields across the country to carry out in-depth academic exchanges and scientific and technological cooperation, share clinical research and innovation achievements, deeply discuss precision oncology based on multidisciplinary standardized comprehensive treatment, and actively promote the development of
disciplines.
In the prostate cancer session 2 held online on the afternoon of November 9, Professor Zeng Hao from West China Hospital of Sichuan University introduced in detail the progress and safety factors of the application of nuclear therapy in the field of metastatic castration-resistant prostate cancer (mCRPC).
Prof.
Hao Zeng
Doctor of Medicine, Professor, Doctoral Supervisor
Deputy Director, Department of Urology, West China Hospital, Sichuan University
Member of the CSCO Prostate Cancer Expert Committee
Member of the CSCO Urothelial Cancer Expert Committee
Member of the Youth Committee of the Urology Branch of the Chinese Medical Association
Member of the International Exchange Committee of the Urology Branch of the Chinese Medical Association
Member of the Youth Committee of the Urogenital Tumor Special Committee of the Chinese Anti-Cancer Association
Leader of the Collaborative Group of Rare Type Kidney Cancer of the Urogenital Tumor Special Committee of the Chinese Anti-Cancer Association
Member and Deputy Secretary of Urological Health Promotion Branch of China Association for the Promotion of International Exchanges in Healthcare
Vice Chairman of the Youth Committee of the Urological Health Promotion Branch of the China Association for the Promotion of International Exchanges in Healthcare
Advances in nuclear therapy in patients with mCRPC bone metastases
mCRPC is the terminal stage of prostate cancer, and about 90% of mCRPC patients have bone metastases, and the overall prognosis of such patients is worse, and the 5-year survival rate is significantly reduced
.
The reason for the poor prognosis of patients with bone metastases in mCRPC is the occurrence of bone-related events (SRE), which not only increases the risk of death but also seriously affects the quality of
life of patients.
It is worth noting that some drug treatments at different stages of mCRPC patients can also lead to SRE, such as osteoporosis caused by new endocrine therapy can cause an increase in SRE, so Professor Zeng said that new clinical treatments are urgently needed to solve this contradiction
.
In recent years, nuclear therapy has shined in the field of prostate cancer and has become an important treatment for bone metastasis
.
The principle is to use the radiation emitted by radionuclides to target the lesion site (targeted binding) to inhibit or kill diseased cells
.
Based on some current clinical trial results, radium-223 and 177Lu-PSMA-617 have demonstrated significant benefits for bone pain symptoms and survival in patients with mCRPC, and have been approved by the US Food and Drug Administration (FDA) for the treatment of mCRPC, of which radium-223 has been launched in China in August 2020 for the clinical treatment
of prostate cancer patients in China.
Professor Zeng introduced the existing mCRPC bone metastasis nuclide therapy drugs including samarium-153, strontium-89, radium-223 and 177Lu-PSMA-617
.
Among them, samarium-153 and strontium-89 can only relieve the symptoms of bone pain and improve SRE.
Radium-223 and 177Lu-PSMA-617 can not only improve SRE symptoms but also prolong the overall survival (OS) of patients, so that patients can obtain more clinical benefits.
Nuclear therapy has unique advantages for bone metastasis mCRPC, but patients often talk about "nuclear" discoloration
.
With the increase of public awareness of radiation protection, most patients believe that nuclear therapy may have some negative effects on physical health, and the surrounding population is also worried that patients receiving nuclear therapy may become an active, open "radioactive source" and fear of it, which also makes patients more reluctant to receive nuclear therapy
.
Professor Zeng pointed out that the concerns of patients and the public about nuclear therapy are unnecessary
.
First, the radiation caused by nuclear therapy and the radiation we receive in our daily lives are essentially the same type of energy
.
Radiation is widely present in all aspects of our lives, according to statistics, the average annual radiation exposure of normal people is 3.
6 mSV, 80% of the exposure comes from the natural environment (radon in the air accounts for 55%), 20% from the human body itself
.
The radiation caused by nuclear therapy will not affect the physical health of the human body, and some effective radiation protection measures (shielding protection, distance protection and time protection) have been taken to control the exposure time and distance to further protect the safety
of patients.
Second, nuclear drugs are also safe
for the population around the patient when used in the norm.
Taking radium-223 as an example, the exposure dose of patients receiving one dose of radium-233 for bone metastases was very small, only 2.
5 MBq, which was much lower than the exposure dose (1110 MBq)
for one bone scan of technetium-99m.
And the penetration of α particles (radium-223) is extremely weak, and paper or skin can block it, so patients can receive nuclear therapy in the outpatient clinic, the surrounding people do not need additional protection, the patient can go home after the injection, and its excrement does not need to be treated
too much.
Finally, several studies have confirmed the short- and long-term safety profile of radium-223
.
In the ALSYMPCA study, the key data of radium-223, radium-223 did not differ significantly from placebo in the incidence of anemia in grade 3/4 (13 versus 13 percent) or in the incidence of neutropenia (2 versus 1 percent
).
。 The results of 3-year follow-up showed that radium-223 had a good long-term safety profile, a ≤3% incidence of myelosuppression (all grades, CTCAE), a very low incidence of secondary malignancies (SPM) (4 in the RA-223 group and 3 in the placebo group), and more patients in the RA-223 group survived (14% vs 7%)
.
In a 7-year REASSURE real-world study, the incidence of drug-related adverse events (AEs) of radium-223 was 38%, of which the incidence of hematological abnormalities was only 13%, and its long-term safety was once again validated
.
In summary, Professor Zeng concluded that the safety of nuclear therapy (especially radium-223) is obvious and trustworthy
.
With the vigorous development of new endocrine drugs (NHA), nuclear therapy and targeted drugs such as PARP inhibitors, mCRPC therapy has also entered the era
of combination therapy.
In order to elucidate the therapeutic efficacy and safety of nuclear therapy in combination with other drugs in the treatment of mCRPC, Professor Zeng conducted an in-depth interpretation
of the data of the following important studies.
Important research on α-particle combination therapy:
●A phase II randomized controlled study of radium-223 in combination with enzalutamide versus enzalutamide in the treatment of mCRPC reported in ASCO GU in 2021 included 47 patients with advanced mCRPC with a median follow-up of 22 months
。 Results showed better long-term benefit of radium-223 plus enzalutamide versus enzalutamide alone, with OS (30.
8 versus 20.
6 months), PSA progression-free survival (PSA-PFS) (8.
9 versus 3.
38 months), and radiographic progression-free survival (rPFS) (11.
5 versus 7.
35 months).
However, its safety results showed that NHA combined with radium-223 increased the incidence
of osteoporosis and fractures in patients.
To solve this problem, the investigators tried to add bone protectors to the original combination treatment regimen, and the safety results of its phase III study (PEACE-3) were published in ASCO in 2021, confirming that radium-223 + enzalutamide combined with bone protectors significantly improved fracture risk
in patients with mCRPC.
Professor Zeng pointed out that the treatment regimen of radium-223 + enzalutamide combined with bone protector can not only significantly improve the long-term survival of patients, but also reduce the incidence of SRE, which is worth paying attention to
.
●PARPi inhibitors have become the standard second-line therapy at the CRPC stage, and radium-223 may be combined with PARPi inhibitors to better treat patients with
mCRPC 。 In a Phase Ib study (NCT03076203) of radium-223 plus nirapa in mCRPC treated with or without chemotherapy reported in ASCO 2020, results showed a better trend in survival benefit in patients receiving combination therapy, with 1 (14%) of 7 subjects having a ≥50% decrease in PSA, 5 (71%) having an alkaline phosphatase (ALP) reduction of ≥30%, and 3 (43%) having ALP reduced by ≥50% at 12 weeks.
None of the participants progressed
to ALP.
More results from phase II/III trials are expected in the future
.
●A phase I/II study of radium-223 in combination with chemotherapy published in 2019 confirmed that the radium-223 plus docetaxel group had a lower incidence of grade 3/4 AEs, a higher safety profile, and a better
trend toward efficacy outcomes compared with docetaxel alone.
The Phase III study (DORA) of radium-223 combined with docetaxel versus docetaxel monotherapy for mCRPC is ongoing, with the primary endpoint being OS, and Professor Zeng said that he expects the results of this study to become the cornerstone of radium-223 combined with chemotherapy in the treatment of
mCRPC.
Important research on β-particle combination therapy:
The PSMAddition study presented at ESMO 2021 is a 177 Phase III clinical trial of Lu-PSMA-617 in combination with standard antiandrotherapy (SOC) versus SOC, which is still ongoing, plans to include 1126 patients with a primary endpoint of blinded assessment of rPFS, secondary endpoints including ≥90% reduction in PSA from baseline, time to progression to mCRPC, PFS, safety and tolerability, and health-related quality of life, which may be 177 The application of Lu-PSMA-617 in frontline treatment provides more reference
.
In addition to combination regimens, other nuclide sequential agents play an important role
in the survival benefit and safety of patients with mCRPC.
Current clinical trial-proven sequential regimens with acceptable safety and efficacy include: NHA post-sequential radium-223, radium-223 sequential chemotherapy, and radium-223 sequential 177Lu-PSMA
.
The results of the ongoing PSMAfore study, which aims to evaluate the efficacy and safety of sequential treatment of 177Lu-PSMA-617 versus NHA in patients with mCRPC who have progressed to NHA and are not receiving chemotherapy, are also of interest
.
In summary, Professor Zeng said that the proportion of bone metastasis in mCRPC patients is as high as 84~92%, which seriously affects the quality of life and survival of patients, and it is urgent to find appropriate management and treatment methods to cope with this problem
.
The new treatment model of nuclear therapy can significantly improve SRE and prolong the survival time of patients with mCRPC, and its short-term/long-term safety has been verified
by many clinical trials and real-world studies.
Based on the controllable safety of nuclear therapy, combination or sequential therapy is possible
.
At present, a number of related phase III trials are underway, and nuclear therapy is expected to create a new situation in the management of prostate cancer patients.
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