CLOVER Study Of PDL1 In NSCLC Demonstrates PCR RNA Expression Analysis Not Equivalent To IHC

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Programmed cell death ligand 1 (PDL1) is approved therapeutic target in lung cancer patients. PDL1 expression above a set threshold must be confirmed by companion immunohistochemistry (IHC) test in order for the patient to be eligible for PDL1 checkpoint inhibition immunotherapy. IHC is the only approved method to detect PDL1 in lung cancer, however it is not the sole method in existence that could be used to test PDL1 levels. A new study compared polymerase chain reaction (PCR) to IHC.

The “CLOVER study” was led by Sergei Tjulandin of the N.N. Blokhin Russian Cancer Research Centre, Moscow, and was published in the journal Scientific Reports. A pairwise comparison of four tests based on the same patient population was performed; one standard Taqman RT-PCR assay using SDHA as a reference gene and three validated PDL1 IHC assays (22C3, SP142, and SP263). The study used 500 archived non-small-cell lung cancer (NSCLC) samples (formalin-fixed, paraffin-embedded blocks) provided by the RUSSCO biobank.

PDL1 RNA expression was detected by PCR in more than 40% of patients, however only 9–45% of these PCR positive patients had corresponding positive IHC assays using the approved thresholds. Of note the SP142 did not appear to be as sensitive as 22C3 and SP263. Overall, the IHC tests correlated well, particularly 22C3 and SP263, but low correlation was observed between the PCR test and each of the three IHC assays.

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“In conclusion, results of the CLOVER study demonstrate a low agreement between PDL1 PCR and IHC expression in NSCLC. PCR RNA expression analysis is not equivalent to IHC methods; however, it may have some potential for identifying PDL1-negative tumors. We suggest that the 22C3 assay could predict the same outcome (positivity or negativity) of the SP263 assay in patients before first-line therapy with a checkpoint inhibitor Patients classified as negative bySP263 or SP142 assays using the corresponding cutoff rule for first-line treatment are highly likely to be classified as negative by any other test. In patients with positive SP263 and SP142 or negative 22C3 repeated testing in second-line treatment could be avoided. The current assessment criteria may change with regard to different cutoff values established from the emerging results of new clinical studies,” stated the authors.