Radiolabeled PD-L1 targeted nanobody 68Ga-THP-APN09 in predicting the efficacy of neoadjuvant immunotherapy combined chemotherapy in resectable non-small cell lung cancer

Introduction: Several clinical trials concerning immunotherapy with checkpoint inhibitor programmed cell death 1 (PD-1)/programmed death ligand-1 (PD-L1) combined chemotherapy in resectable non-small cell lung cancer (NSCLC) indicated compelling results, with major pathological response (MPR) rate higher than 55%. However, the request of the method screening patients who might benefit from neoadjuvant immunotherapy combined chemotherapy is still urgent. Here, we report a study to evaluate the predictive value of baseline PD-L1 targeted nanobody, ⁶⁸Ga-THP-APN09 PET/CT in neoadjuvant immunotherapy combined with chemotherapy of resectable NSCLC.

Methods: Patients with resectable NSCLC (n = 50) enrolled in this prospective study received baseline paired ⁶⁸Ga-THP-APN09 PET/CT and ¹⁸F-FDG PET/CT. After 2–4 cycles of toripalimab plus nab-paclitaxel and cisplatin, surgery was performed if R0 resection was available. The major pathologic response (MPR) state of the post-operative specimen was recorded. The imaging parameters of the ⁶⁸Ga-THP-APN09 PET/CT, ¹⁸F-FDG PET/CT and CT between the MPR and non-MPR groups and their predictive efficacy of MPR were compared.

Results: Among 50 patients, 34 patients were responsive, among them, 30 underwent surgery, 26 gained MPR, 4 gained non-MPR；16 patients were not responsive, among them, 11 underwent surgery, 1 gained MPR, 10 gained non-MPR. Five patients who were not responsive could not undergo R0 resection after combined therapy were enrolled in the non-MPR group. The SUV_max and tumour-to-blood pool (TBR) of baseline ⁶⁸Ga-THP-APN09 in the MPR group were significantly higher than those in the non-MPR group, as 3.5 ± 0.8 vs. 2.5 ± 0.6 (P<0.001) and 2.6 ± 0.6 vs. 2.6 ± 1.0 (P<0.001). TheΔSULpeak% of ¹⁸F-FDG exhibited differences between the MPR and non-MPR groups as well, as 79.5% ± 16.5% vs. -14.0% ± 84% (P<0.001), while baseline ¹⁸F-FDG PET/CT parameters could barely differentiate the two groups. The areas under the ROC curves of SUVmax in ⁶⁸Ga-THP-APN09 PET/CT 0.85 in predicting MPR.

Conclusions: Baseline ⁶⁸Ga-THP-APN09 PET/CT has a potential to predict the pathological response of neoadjuvant immunotherapy combined with chemotherapy in patients with resectable NSCLC, whose efficacy is no worse than that of therapy evaluations employing baseline and follow-up ¹⁸F-FDG PET/CT examinations.

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