After ASCO GU 2022: Interpretation and reflection on mCSPC real-world data

A022 From February 17th to 19th, the ASCO-GU conference was held offline in San Francisco, USA.
On the first day, it not only released the blockbuster results of several prospective phase III clinical studies of prostate cancer, but also reported a number of mCSPC real-world research
.

In recent years, ADT combined with new endocrine or docetaxel and other new combination therapy has shown significant benefits compared with ADT alone or ADT combined with first-generation non-steroidal anti-androgen therapy in patients with advanced prostate cancer, which has promoted the reform of treatment concepts and treatment methods
.

In 2021, domestic and international guidelines will officially no longer use ADT alone as the standard treatment option for mHSPC.
Except for the combined contraindications, once mHSPC is diagnosed, the new combination therapy based on ADT is preferentially recommended
.

This paper specially invites Professor Zeng Hao from West China Hospital of Sichuan University to interpret and comment on the mCSPC real-world research updated by the conference
.

(1) Distribution of mCSPC treatment options and longitudinal changes Abstract #183 Real-world observation of mCSPC patients using novel combination therapy This is a retrospective cohort observational study based on the Optum Research database in the United States, from January 1, 2014 to June 2019 During the 30-day period, a total of 4,675 mCSPC patients who received treatment were included, of which 2,928 were treated by oncologists and urologists, 766 were treated by urologists only, and 932 were treated by oncologists only.

.

The results showed that for the entire mCSPC patient population, the proportion of ADT + new endocrine therapy increased significantly from 2014 to 2019, and the use of docetaxel + ADT, first-generation NSAIDs + ADT, and ADT alone showed varying degrees.
drop
.

Similar trends were observed for patients with different metastases
.

This study shows that the proportion of 2L treatment options is mainly NHT, but it is difficult to interpret the consideration of sequential selection because it is unclear which treatment progress of patients, especially for patients with a history of NHT treatment
.

But interestingly, the most common treatment option for 3L therapy is NHT, followed by ADT combined with cabazitaxel/Ra-223
.

Interpretation and thinking: The whole-course management of patients with new combination therapy as the first-line treatment of mCSPC has always been a practical issue that clinicians are concerned about
.

Although the quantitative distribution of bone metastases was not reported for the first-line treatment options for mCSPC, it was surprising that patients with bone metastases only or bone with lymph node metastases were slightly more likely to receive intensive therapy than those with visceral metastases
.

A higher proportion of the visceral metastases cohort received triple therapy with NHT + docetaxel + ADT (Fig.
3 "Other" treatment)
.

The follow-up sequential treatment selection and the distribution of different treatment sequences and follow-up data still need further analysis to assist clinical optimization of treatment strategies
.

(2) Treatment response and outcome follow-up of mCSPC The real-world "quartet" of HUNTSMAN Cancer Center - a single-center retrospective study with multi-dimensional data analysis Abstract #186 The baseline genetic characteristics study of newly diagnosed high-tumor mCSPC patients included a total of 304 mCSPC patients, the most common The mutant genes are TP53, PTEN and SPOP
.

Compared with non-newly diagnosed high tumor patients, 100 newly diagnosed high tumor patients (CHAARTED criteria) had significantly higher TP53 and BRCA2 mutation rates at baseline
.

The correlation between the difference in baseline characteristics and the difference in gene mutation between the two groups needs to be further analyzed
.

Abstract#133 Multivariate analysis and reflections on PFS and OS in newly diagnosed high-tumor mCSPC patients receiving ADT+NHT/chemotherapy, 85 newly-diagnosed high-tumor mCSPC patients were included in this analysis, 45 of whom received ADT+NHT, 40 People who received ADT + docetaxel had median PFS of 23 m and 14 months, and median OS of 63 months and 36 months, respectively
.

Multivariate analysis showed that receiving novel combination therapy (NHT or docetaxel) was the only factor that significantly affected PFS, but not OS
.

Interpretation and thinking: Indirect comparison of the median OS results of PEACE-1 (Abi+Doce+ADT vs Doc+ADT: 61m vs 42m) leads to more in-depth and valuable thinking: mCSPC triple intensive therapy released by PEACE-1 Is there a dominant therapeutic component in Abi? If Abi is the main effect-producing factor at this stage, is this triple enhancement really due to Abi+ADT dual therapy
.

This study preliminarily found that the OS of Abi+ADT was comparable to that of Abi+Doce+ADT.
Therefore, relevant studies still need to be carried out in the future to confirm the value of triple therapy Doce, and it is necessary to comprehensively consider adverse reactions and quality of life
.

The conference 136# abstract compared the efficacy of first-line intensive therapy and new combination therapy in mCSPC through meta-analysis.
The results showed that first-line triple-combination intensive therapy significantly delayed disease progression compared with first-line chemotherapy + ADT, and first-line new endocrine + ADT still needs further data generation and analysis
.

Abstract 132# also conducted a meta-analysis between triple intensive therapy and new combination therapy, the results suggest that triple intensive therapy may bring better rPFS and OS benefits but at the same time higher treatment toxicity.
and low tumor patients still have advantages
.

How to carry out patient selection and treatment selection to achieve the efficacy and safety benefits of patients still needs to provide more clues from the long-term follow-up results of RCT and post-hoc comprehensive analysis combined with clinical insights
.

Abstract#123 Analysis of baseline and survival outcomes for patients with superior PSA response (PSA≤0.
2 ng/ml) after receiving novel combination therapy Previous post-hoc analysis of RCTs showed that mCSPC achieved PSA≤0.
2 ng/ml after first-line intensive therapy ml was significantly associated with improved OS compared with the unattained non-optimized response population
.

This analysis also showed consistency in the real world, whether it was NHT+ADT or docetaxel+ADT, patients who achieved PSA≤0.
2 ng/ml had a higher PFS than those who did not (60.
6 vs 13.
2m, P<0.
001).
And OS (94.
9 vs 35.
2m, P<0.
001) benefit was more significant
.

The results of multivariate analysis showed that achieving PSA≤0.
2 ng/ml and the choice of intensive treatment were the factors that significantly affected rPFS and OS
.

Taking the achievement of superior response as a stratification factor, it was found that there were differences in some baseline indicators between the two groups, but there was no significant difference in the results of genetic testing
.

Interpretation and thinking: As early as in the SWOG9346 study, it was proposed that after 7 months of ADT treatment for mCSPC, the PSA decreased to 4ng/ml and 0.
2ng/ml, and the patients could be divided into 3 prognosis groups, and the prognosis of the patients was lower than 0.
2ng/ml.
best
.

With the new combination therapy entering the first line, the post-hoc analysis of the CHAARTED, LATITUDE and TITAN studies also reported that achieving PSA≤0.
2ng/ml significantly reduced the risk of death in patients, suggesting that the response after treatment is an important prognostic indicator regardless of the treatment
.

86 # Abstract A longitudinal observational study in Canada in which 140 patients were assessed for time to "Beyond ADT" showed that 81% of patients received intensive therapy within 3 months of receiving ADT, and 19% received ADT alone for more than Treatment intensification was carried out after 3 months, and the reasons for treatment intensification of different durations and the outcome of patients need to be further analyzed
.

In the SWOG9346 study, the immediate or appropriate delay of ADT was explored, which also led to decision-making thinking about current treatment options: under the premise that the first-line first-line election is uncertain, you can try traditional drug treatment for 3 months.
If the PSA fails to decrease If it is below 0.
2, immediately switch to a new combination therapy mode, and still more than 70% of patients can reach below 0.
2
.

This is an exploratory reflection on the real-world rational selection mode of novel combination therapy regimens, pending further data generation and analysis
.

Abstract#121 Survival analysis of mCSPC after first-line use of novel combination therapy and mCRPC after first-line use of novel combination therapy.
From 2011 to 2020, a total of 172 patients with metastatic prostate cancer (mCSPC+mCRPC) used first-line novel endocrine combined with ADT to progress
.

The results suggest that regardless of the stage of first-line NHT use, the real-world observational OS after progression is less than 2 years, the OS after first-line NHT progression for mCSPC reaches 23 months, and the first-line progression for mCRPC reaches 17 months, with no statistical difference
.

The reasons for the researchers' analysis may include that treatments beyond the AR signaling pathway and the Taxanes-mediated microtubule inhibition pathway have not been widely used in clinical practice; there is no prospective study to confirm the difference in treatment between different treatment sequences
.

Interpretation and thinking: In this study, it was observed that the OS of the new combination therapy with NHT+ADT in the first-line treatment of mCSPC and mCRPC was equivalent after progression, which led to thinking: This study suggests that the follow-up survival extension space is equivalent, how to prolong the first-line NHT+ADT as much as possible.
Treatment time may be the key to prolonging patient survival; new treatment pathways are still the direction to be explored; the sample size of patients with mCSPC progression is small, and larger samples and long-term follow-up data are still needed
.

At the same time, with the increasing trend of first-line use of NHT in mCSPC, an RCT study should be carried out after the progress of first-line NHT+ADT in mCSPC to assist in the optimization of the whole management process.

.


This study did not disclose the detailed sequential selection and the prognosis of different treatment groups.
We can turn to Abstract 60#, a Canadian multi-center retrospective analysis.
It can be seen that the first-line treatment of mCSPC receiving NHT+ADT progressed to the sequential treatment of mCRPC and follow up
.

Although this study is also limited by a small sample size because mCSPC patients receiving NHT+ADT have not yet progressed, the observed patients are mainly cases of progression within 2 years, but it still brings important real-world findings: real-world NHT After the progression of +ADT, the sequence was docetaxel chemotherapy, NHT with different mechanisms, and targeted radiation therapy
.

Interestingly, although the PSA response rate of →NHT+ADT was weaker than that of the NHT naïve RCT in the mCRPC first-line use of NHT, it still showed a good PSA response compared with other treatments
.

The analysis of OS still needs to expand the sample size and longer-term follow-up
.

In addition to NHT+ADT, first-line docetaxel chemotherapy+ADT for mCSPC is also one of the standard standard treatments.
Abstract107# An Italian multicenter, prospective longitudinal observational study shared the observation results of the progression pattern of mCSPC after receiving chemotherapy[hz1]
.

The study included 166 newly diagnosed mCSPC patients who received docetaxel chemotherapy, 81% completed 6 cycles of treatment, the median follow-up time was 27.
9 months, and the median time to castration resistance (TTCR) for all patients was 14.
3 month, the median survival (OS) was 41 months, and the median survival from mCRPC diagnosis was 19.
6 months
.

122 patients had PSA or radiographic progression events, of which 60% developed new metastases (NMS)
.

Although the NMS group had a higher proportion of lymph node progression and bone progression than the non-NMS group, the median TTCR, OS (NMS vs nonNMS: 34.
8m vs 41.
3m) and median survival at mCRPC diagnosis (14.
8m vs 20.
7m) between groups ) showed no significant difference
.

The results of the study suggest that the main progression mode of mCSPC patients receiving chemotherapy + ADT is imaging progression, and whether the appearance of new lesions has prognostic value still needs further follow-up
.

After the interpretation of the "Quartet" and other research data that have been extended at the same time, we are more thinking: whether the first-line use of new combination therapy in mCSPC will affect subsequent treatment and the application of new treatment methods after entering CRPC still requires large samples and long-term follow-up.
Observations are worth exploring and summarizing
.

Recommendations from other real-world studies of mCSPC: Abstract16# Multinational online patient survey of 15,824 patients with metastatic prostate cancer had a higher proportion of symptom-driven diagnoses; endocrine therapy was the most common treatment modality for metastatic prostate cancer, in the United States and Germany Nearly 50% of metastatic patients underwent prostatectomy (details not shown)
.

Abstract43#A multi-center retrospective longitudinal observational study in the United States shows that the first-line use of Apa in mCSPC is comparable to RCT in achieving PSA90 response at 6 months and 12 months; different NHTs have differences in rapid and deep response, and APA achieves a higher proportion of PSA90 response earlier than Enza
.

Abstract45# A single-center survey of 39 patients with mCSPC shows that out-of-pocket ratio, symptoms and tumor burden are important factors affecting first-line selection
.

Abstract109# Feasibility of serial SBRT in patients with oligometastatic disease diagnosed by PET (Fluciclovine/PSMA/Choline) and PSA response independent of systemic therapy
.

Conclusion Real-world research is not only the verification and practice of RCTs, but also the beginning of a new round of evidence-based exploration in practice by clinicians
.

Every doctor has never stopped striving for the maximum clinical benefit for every patient in clinical diagnosis and treatment, looking forward to the generation of more high-quality real-world data! Interpretation and Expert Comments Professor Zeng Hao, Sichuan University West China Hospital, MD, professor, doctoral supervisor, deputy director of the department Committee Member Member of the Youth Committee of the Urological and Male Genital Oncology Committee of the China Anti-Cancer Association Member of the Prostate Cancer Expert Committee Member of the CSCO Urothelial Cancer Expert Committee Member of the Standing Committee of the Sichuan Urology Specialized Committee Deputy Head of the Oncology Group of the Sichuan Urology Specialized Committee