Trial Outcomes & Findings for Sensitivity of PDL-1-analysis From Pleural Effusion in Non-small Cell Lung Cancer (NCT NCT02855281)

NCT ID: NCT02855281

Last Updated: 2021-03-05

Results Overview

Number/prevalence of PD-L1-positive patients according to immunohistochemistry (IHC) of pleural biopsy.

• Recruitment status: COMPLETED
• Target enrollment: 50 participants
• Primary outcome timeframe: At baseline
• Results posted on: 2021-03-05

Participant Flow

Clinical routine patients presenting with (suspected malignant) pleural effusion and indication for pleural puncture were considered for enrollment. Patients with confirmed malignancy of pleural effusion were actually enrolled.

Participant milestones

Measure	Malignant Pleural Effusion Patients with confirmed malignant pleural effusion
Overall Study STARTED	50
Overall Study COMPLETED	50
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sensitivity of PDL-1-analysis From Pleural Effusion in Non-small Cell Lung Cancer

Baseline characteristics by cohort

Measure	Malignant Pleural Effusion n=50 Participants patients with confirmed malignant pleural effusion
Age, Continuous	72.5 years n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	33 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	50 Participants n=5 Participants
BMI	25.7 kg/m2 n=5 Participants
smoking status never	7 Participants n=5 Participants
smoking status ex-smoker	28 Participants n=5 Participants
smoking status current smoker	15 Participants n=5 Participants
Histology Type NSCLC - Adeno carcinoma	33 Participants n=5 Participants
Histology Type NSCLC - Squamous cell carcinoma	7 Participants n=5 Participants
Histology Type NSCLC - large-cell neuroendocrine carcinoma	1 Participants n=5 Participants
Histology Type SCLC	4 Participants n=5 Participants
Histology Type SCLC + Adeno carcinoma	1 Participants n=5 Participants
Histology Type Non-Hodgkin Lymphoma	1 Participants n=5 Participants
Histology Type Sarcomatoid Mesothelioma	1 Participants n=5 Participants
Histology Type Ambiguous histology	2 Participants n=5 Participants
Cancer Stage (UICC 8th ed.) IA2	1 Participants n=5 Participants
Cancer Stage (UICC 8th ed.) IB	1 Participants n=5 Participants
Cancer Stage (UICC 8th ed.) IIB	3 Participants n=5 Participants
Cancer Stage (UICC 8th ed.) IIIA	2 Participants n=5 Participants
Cancer Stage (UICC 8th ed.) IIIB	2 Participants n=5 Participants
Cancer Stage (UICC 8th ed.) IVA	24 Participants n=5 Participants
Cancer Stage (UICC 8th ed.) IVB	15 Participants n=5 Participants
Cancer Stage (UICC 8th ed.) Unknown	1 Participants n=5 Participants
Cancer Stage (UICC 8th ed.) III-IV (IMIG classification)	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: At baseline

Population: Thoracoscopy was performed in all fifty patients. PD-L1 analysis of pleural tissue was indicated in all samples with evidence of tumor cells (n=40), excluding cases with small-cell lung cancer (n=2). Mainly due to insufficient sample material (low tumor cell count) (n=3), PD-L1 analysis could actually be performed in 35 pleural tissue cases.

Number/prevalence of PD-L1-positive patients according to immunohistochemistry (IHC) of pleural biopsy.

Outcome measures

Measure	Number of PD-L1-positive Samples in IHC n=35 Participants For the assessment of potentially therapy-relevant PD-L1 expression levels, two different threshold levels of PD-L1 expression were considered as per the differing approval status (TPS ≥50% and TPS≥1%). Regarding detection of malignancy and PD-L1-positivity, results were defined as negative where the tests were not feasible or in case of inconclusive findings.	Sensitivity and Specificity of PD-L1 Detection in Pleural Effusion (TPS ≥1%) Sensitivity and specificity of PD-L1 detection in pleural effusion. PD-L1 expression with a TPS ≥ 1% was defined as PD-L1 positive.
PD-L1 Prevalence IHC PD-L1 expression with a TPS ≥ 1% was defined as PD-L1-positive · PD-L1 positive	21 Participants	—
PD-L1 Prevalence IHC PD-L1 expression with a TPS ≥ 1% was defined as PD-L1-positive · PD-L1 negative	14 Participants	—
PD-L1 Prevalence IHC PD-L1 expression with a TPS ≥ 50% was defined as PD-L1-positive · PD-L1 positive	8 Participants	—
PD-L1 Prevalence IHC PD-L1 expression with a TPS ≥ 50% was defined as PD-L1-positive · PD-L1 negative	27 Participants	—

PRIMARY outcome

Timeframe: At baseline

Population: Pleural puncture was performed in all fifty patients. PD-L1 analysis of pleural effusion was indicated in all samples with evidence of tumor cells (n=36), excluding cases with small-cell lung cancer (n=3). Mainly due to insufficient sample material (low tumor cell count) (n=7) or technical issue (n=1), PD-L1 analysis could actually be performed in 25 pleural effusion cases.

Number/prevalence of PD-L1-positive patients according to immunocytochemistry (ICC) of pleural aspirate

Outcome measures

Measure	Number of PD-L1-positive Samples in IHC n=25 Participants For the assessment of potentially therapy-relevant PD-L1 expression levels, two different threshold levels of PD-L1 expression were considered as per the differing approval status (TPS ≥50% and TPS≥1%). Regarding detection of malignancy and PD-L1-positivity, results were defined as negative where the tests were not feasible or in case of inconclusive findings.	Sensitivity and Specificity of PD-L1 Detection in Pleural Effusion (TPS ≥1%) Sensitivity and specificity of PD-L1 detection in pleural effusion. PD-L1 expression with a TPS ≥ 1% was defined as PD-L1 positive.
PD-L1 Prevalence ICC PD-L1 expression with a TPS ≥ 1% was defined as PD-L1-positive · PD-L1 positive	19 Participants	—
PD-L1 Prevalence ICC PD-L1 expression with a TPS ≥ 1% was defined as PD-L1-positive · PD-L1 negative	6 Participants	—
PD-L1 Prevalence ICC PD-L1 expression with a TPS ≥ 50% was defined as PD-L1-positive · PD-L1 positive	13 Participants	—
PD-L1 Prevalence ICC PD-L1 expression with a TPS ≥ 50% was defined as PD-L1-positive · PD-L1 negative	12 Participants	—

PRIMARY outcome

Timeframe: At baseline

Based on all cases where PD-L1 analysis was indicated and sucessful (i.e. giving definite results), the immunocytochemistry analysis of PE was compared with the immunohistochemistry analysis of pleural tissue.Two different alternatives were calculated:

• PD-L1 expression with a TPS ≥50% was defined as PD-L1-positive.
• PD-L1 expression with a TPS ≥1% was defined as PD-L1-positive.

Outcome measures

Measure	Number of PD-L1-positive Samples in IHC n=21 Participants For the assessment of potentially therapy-relevant PD-L1 expression levels, two different threshold levels of PD-L1 expression were considered as per the differing approval status (TPS ≥50% and TPS≥1%). Regarding detection of malignancy and PD-L1-positivity, results were defined as negative where the tests were not feasible or in case of inconclusive findings.	Sensitivity and Specificity of PD-L1 Detection in Pleural Effusion (TPS ≥1%) n=21 Participants Sensitivity and specificity of PD-L1 detection in pleural effusion. PD-L1 expression with a TPS ≥ 1% was defined as PD-L1 positive.
PD-L1 Detection in Pleural Effusion Based on All Cases With Successful PD-L1 Analysis Sensitivity	100 percent Interval 46.0 to 100.0	86 percent Interval 56.0 to 97.0
PD-L1 Detection in Pleural Effusion Based on All Cases With Successful PD-L1 Analysis Specificity	63 percent Interval 36.0 to 84.0	43 percent Interval 12.0 to 80.0
PD-L1 Detection in Pleural Effusion Based on All Cases With Successful PD-L1 Analysis positive predictive value	45 percent Interval 18.0 to 75.0	75 percent Interval 47.0 to 92.0
PD-L1 Detection in Pleural Effusion Based on All Cases With Successful PD-L1 Analysis negative predictive value	100 percent Interval 66.0 to 100.0	60 percent Interval 17.0 to 93.0

SECONDARY outcome

Timeframe: At baseline

Based on all cases where PD-L1 analysis was indicated, the immunocytochemistry analysis of PE was compared with the immunohistochemistry analysis of pleural tissue.Two different alternatives were calculated:

• PD-L1 expression with a TPS ≥50% was defined as PD-L1-positive.
• PD-L1 expression with a TPS ≥1% was defined as PD-L1-positive. In both instances, cases where PD-L1 analysis could not be performed were defined as negative.

Outcome measures

Measure	Number of PD-L1-positive Samples in IHC n=31 Participants For the assessment of potentially therapy-relevant PD-L1 expression levels, two different threshold levels of PD-L1 expression were considered as per the differing approval status (TPS ≥50% and TPS≥1%). Regarding detection of malignancy and PD-L1-positivity, results were defined as negative where the tests were not feasible or in case of inconclusive findings.	Sensitivity and Specificity of PD-L1 Detection in Pleural Effusion (TPS ≥1%) n=31 Participants Sensitivity and specificity of PD-L1 detection in pleural effusion. PD-L1 expression with a TPS ≥ 1% was defined as PD-L1 positive.
PD-L1 Detection in Pleural Effusion Based on All Cases With Indication for PD-L1 Analysis Sensitivity	71 percent Interval 30.0 to 95.0	71 percent Interval 44.0 to 89.0
PD-L1 Detection in Pleural Effusion Based on All Cases With Indication for PD-L1 Analysis Specificity	71 percent Interval 49.0 to 87.0	64 percent Interval 36.0 to 86.0
PD-L1 Detection in Pleural Effusion Based on All Cases With Indication for PD-L1 Analysis positive predictive value	42 percent Interval 16.0 to 71.0	71 percent Interval 44.0 to 89.0
PD-L1 Detection in Pleural Effusion Based on All Cases With Indication for PD-L1 Analysis negative predictive value	89 percent Interval 65.0 to 98.0	64 percent Interval 36.0 to 86.0

SECONDARY outcome

Timeframe: At baseline

Comparing the immunocytochemistry (ICC) analysis of pleural effusion concerning the detection of malignant tumor cells as compared to the immunohistochemistry analysis of pleural tissue. Seven cases of ICC analysis with inconclusive results were defined as negative.

Outcome measures

Measure	Number of PD-L1-positive Samples in IHC n=50 Participants For the assessment of potentially therapy-relevant PD-L1 expression levels, two different threshold levels of PD-L1 expression were considered as per the differing approval status (TPS ≥50% and TPS≥1%). Regarding detection of malignancy and PD-L1-positivity, results were defined as negative where the tests were not feasible or in case of inconclusive findings.	Sensitivity and Specificity of PD-L1 Detection in Pleural Effusion (TPS ≥1%) Sensitivity and specificity of PD-L1 detection in pleural effusion. PD-L1 expression with a TPS ≥ 1% was defined as PD-L1 positive.
Tumor Cell Detection in Pleural Effusion Sensitivity	83 percent Interval 67.0 to 89.0	—
Tumor Cell Detection in Pleural Effusion Specificity	70 percent Interval 35.0 to 92.0	—
Tumor Cell Detection in Pleural Effusion positive predictive value	92 percent Interval 76.0 to 98.0	—
Tumor Cell Detection in Pleural Effusion negative predictive value	50 percent Interval 24.0 to 76.0	—

Adverse Events

NSCLC With Pleural Effusion

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Lars Hagmeyer

Hospital Bethanien Solingen, Clinic of Pneumology and Allergology, Center for Sleep Medicine and Respiratory Care, Solingen, Germany

Phone: 0212636004

Email: institut@klinik-bethanien.de

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place