UMIN-ICDS Clinical Trial

Public title

Bone metastasis response to immune checkpoint inhibitors in cancer patients: a systematic review

Acronym

Bone metastasis response to immune checkpoint inhibitors in cancer patients: a systematic review

Scientific Title

Bone metastasis response to immune checkpoint inhibitors in cancer patients: a systematic review

Scientific Title:Acronym

Bone metastasis response to immune checkpoint inhibitors in cancer patients: a systematic review

Region

Japan

Europe

Condition

bone metastases of various cancers

Classification by specialty

Hematology and clinical oncology

Orthopedics

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

Bone is a common site of metastasis, and many types of cancer (e.g., myeloma, kidney, melanoma, breast, lung, prostate, etc.) preferentially metastasize to bone, correlating with poor prognosis [7]. More than 50% of all cancer patients develop bone metastases [8]. More than 88% of metastatic prostate cancer patients metastasize to bone, and 70% of metastatic breast cancer patients metastasize to bone [8,9]. Bone metastases can cause skeletal related events, such as pain, pathological fractures, compression of the spinal cord, hypercalcemia [10]. Although surgery for impending fractures is a standard approach [11], prophylactic surgery is not always beneficial to patients because of the poor general condition of patients with bone metastases, and furthermore, surgery may delay systemic treatment [12]. If the response of ICI for bone metastases (Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [13], MD Anderson Cancer Center (MDA) criteria [14][Table 2]) is partial response (PR) or complete response (CR), surgical treatments may be unnecessary for impending fractures [15]. However, only 1% (6/561) of the studies analyzing immunotherapies for breast, prostate, lung, and melanoma reported specific response for bone metastases [16]. Thus, the impact of ICI therapy on bone metastases remains unclear.
Therefore, we performed a systematic review of studies reporting response of ICIs specific for bone metastases of various cancers.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

response rate of ICI for bone metastases (RECIST[13], MDA criteria [14][Table 2]).

Key secondary outcomes

Study type

Others,meta-analysis etc

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Studies reporting response rates specific for bone metastases in patients treated with ICIs were included;

Key exclusion criteria

reports of fewer than 5 cases were excluded. Only English- and Japanese-language literature was included, with no restriction on the year of publication. Only human subjects were included; animals were excluded.

Target sample size

Name of lead principal investigator

1st name	Shinji
Middle name
Last name	Tsukamoto

Organization

Nara Medical University

Division name

Department of Orthopaedic Surgery

Zip code

634-8521

Address

840, Shijo-cho, Kashihara-city Nara 634-8521, Japan

TEL

+81-744-22-3051

Email

shinji104@mail.goo.ne.jp

Name of contact person

1st name	Shinji
Middle name
Last name	Tsukamoto

Organization

Nara Medical University

Division name

Department of Orthopaedic Surgery

Zip code

634-8521

Address

840, Shijo-cho, Kashihara-city Nara 634-8521, Japan

TEL

+81-744-22-3051

Homepage URL

Email

shinji104@mail.goo.ne.jp

Institute

Department of Orthopaedic Surgery
Nara Medical University

Institute

Department

Personal name

Organization

Department of Orthopaedic Surgery
Nara Medical University

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Department of Orthopaedic Surgery Nara Medical University

Address

840, Shijo-cho, Kashihara-city Nara 634-8521, Japan

Tel

+81-744-22-3051

Email

shinji104@mail.goo.ne.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2024

Year

02

Month

26

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

340

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2024

Year

02

Month

26

Day

Date of IRB

2024

Year

02

Month

26

Day

Anticipated trial start date

2024

Year

02

Month

26

Day

Last follow-up date

2024

Year

03

Month

02

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Search results
Of the 699 studies identified by the search, nine were ultimately included in the present study (Figure 1, Table 3)[12,19-26]. No RCTs were available for these nine studies.

Methodological quality of the included studies
We assessed the quality of individual studies using the RoBANS tool and found an overall moderate risk of bias (Table 4).

Results
The MDA criteria assess bone-specific response to treatment. It can evaluate a variety of changes in all types of bone metastatic lesions: osteolytic, osteoblastic, and mixed (Table 2)[14]. On the other hand, RECIST can only evaluate the size of osteolytic lesions and not osteosclerotic changes [13]. Furthermore, osteoblastic bone lesions are considered unmeasurable [13].
Lung cancer is histologically classified into small cell lung cancer and non-small cell lung cancer. Non-small cell lung cancer further consists of non-squamous carcinomas, such as adenocarcinoma and large cell carcinoma, and squamous cell carcinoma [27]. Among patients with non-small cell lung cancer treated with ICI with or without bone-modifying agents (N = 188), 13-44% had CR or PR by MDA criteria (Table 3) [12,20-22,24]. In patients with non-small cell lung cancer treated with ICI with bone-modifying agents (N = 43), 44-78% had CR or PR by MDA criteria (Table 3)[12,22]. In patients with non-small cell lung cancer treated with ICI alone (N = 20), 0-17% had CR or PR on MDA criteria (Table 3)[12,22]. In patients with melanoma treated with ICIs and denosumab (N = 29), 62% had CR or PR on MDA criteria [25]. In patients with renal cell carcinoma (N = 21), 5% showed CR or PR by RECIST criteria [23], and in patients with urothelial carcinoma (N = 32), 7-28% showed CR or PR by RECIST criteria [19,26].

Registered date

2024

Year

02

Month

26

Day

Last modified on

2024

Year

02

Month

26

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000061289