SP263 and 22C3 Assays Show Similar Predictive Value for Atezolizumab in NSCLC

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Findings from a phase 3 study (NCT02486718) suggest that both the VENTANA SP263 and Dako 22C3 (SP263 and 22C3) assays can be utilized to identify patients with early-stage non–small cell lung cancer (NSCLC) who are most likely to experience benefit from adjuvant atezolizumab (Tecentriq).¹

According to results published in the Journal for Immunotherapy of Cancer, high concordance and a comparable clinical predictive value of atezolizumab at validated PD-L1 thresholds were observed using the SP263 and 22C3 assays. The study utilized tumor samples from the phase 3 IMpower010 study (NCT02486718) which evaluated the safety and efficacy of atezolizumab vs best supportive care (BSC) following adjuvant cisplatin-based chemotherapy in patients with completely resected stage IB-IIIA NSCLC. These samples were used to compare the 2 PD-L1 immunohistochemistry assays, SP263 and 22C3.

Investigators assessed the assays to see how they differentiated in regard to the identification of PD-L1 patient subgroups, as well as their predictive value for adjuvant atezolizumab vs BSC among patients with resectable early-stage NSCLC.

The SP263 assay evaluated PD-L1 expression by evaluating the percentage of tumor cells with any membranous PD-L1 staining, and the 22C3 assay assessed PD-L1 expression using the percentage of viable tumor cells which showed the partial or complete membranous PD-L1 staining.

This study was a global, multicenter, open-label, randomized, phase 3 trial. The safety and efficacy of 16 cycles of atezolizumab were compared with BSC in patients with stage IB-IIIA NSCLC following resection and adjuvant chemotherapy. One cycle lasted for a duration of 21 days. Once patients completed up to 4 cycles of adjuvant cisplatin-based chemotherapy, they were randomized 1:1 to receive either atezolizumab or BSC for up to 16 cycles.²

The primary end point of the study was disease-free survival (DFS) and secondary end points included overall survival, percentage of patients with adverse events, percentage of patients with anti-therapeutic antibodies to atezolizumab, and pharmacokinetics.

Looking at the concordance at the PD-L1-positive threshold, for which the SP263 assay tumor cell (TC) was ≥1% and the 22C3 assay tumor proportion score (TPS) was ≥ 1%, findings showed concordance between assays for 83% of the samples.1 Results were also concordant between assays at the PD-L1-high cut-off (SP263: TC ≥ 50%; 22C3: TPS ≥ 50%), for 92% of samples.

Regardless of which of 2 tests were used to measure PD-L1, the assays were comparable in regard to DFS for atezolizumab vs BSC for PD-L1-positive disease (TC ≥ 1% by SP263: HR, 0.58; 95% CI, 0.40-0.85; TPS ≥ 1% by 22C3: HR, 0.65; 95% CI, 0.45-0.95) and PD-L1-high (TC ≥ 50% by SP263: HR, 0.27; 95% CI, 0.14-0.53; TPS ≥ 50% by 22C3: HR, 0.31; 95% CI, 0.16-0.60) subgroups.

Overall, researchers concluded that these 2 assays for PD-L1 in early-stage NSCLC can both be used to choose patients who are likely to do well with atezolizumab.

REFERENCES:

Zhou C, Srivastava MK, Xu H, et al. Comparison of SP263 and 22C3 immunohistochemistry PD-L1 assays for clinical efficacy of adjuvant atezolizumab in non-small cell lung cancer: results from the randomized phase III IMpower010 trial. J Immunother Cancer. 2023;11(10):e007047. doi:10.1136/jitc-2023-007047

Study to assess safety and efficacy of atezolizumab (MPDL3280A) compared to best supportive care following chemotherapy in patients with lung cancer [IMpower010]. ClinicalTrials.gov. Updated November 2, 2023. Accessed December 21, 2023. https://clinicaltrials.gov/study/NCT02486718