Are anti-PD1 and anti-PD-L1 alike? The non-small-cell lung cancer paradigm

Banna, Giuseppe Luigi; Cantale, Ornella; Bersanelli, Melissa; Re, Marzia Del; Friedlaender, Alex; Cortellini, Alessio; Addeo, Alfredo

doi:10.4081/oncol.2020.490

Cited by 43 publications

(34 citation statements)

References 60 publications

(128 reference statements)

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“…Together, these two results might imply that anti‐PD1 antibodies induce stronger antitumoral therapy 20 . These differences might also derive from heterogeneous immunogenicity of the antibodies themselves, eliciting neutralizing antibodies against the anti‐PD1 or ant‐PD‐L1 antibodies that could dampen their activity to different extents 21 …”

Section: Discussionmentioning

confidence: 99%

Anti‐PD1 versus anti‐PD‐L1 immunotherapy in first‐line therapy for advanced non‐small cell lung cancer: A systematic review and meta‐analysis

2021

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Background Due to the increasing number of trials with immune checkpoint inhibitors (ICIs) in the first‐line therapy of non‐small cell lung cancer (NSCLC) patients, we performed a systematic review and meta‐analyses to investigate the difference between anti PD‐1 and PD‐L1 antibodies, used alone or in combination with chemotherapy, through adjusted indirect analysis to minimize the potential bias regarding overall survival (OS), progression‐free survival (PFS), overall response rate (ORR) and grade 3–5 adverse events (AEs). Methods A systematic review of studies reporting clinical outcomes and toxicity associated with first‐line therapy employing anti‐PD1 or anti‐PD‐L1 antibodies alone, or in combination with chemotherapy, to treat metastatic, treatment‐naïve NSCLC patients was performed. Primary outcomes were OS, PFS, ORR and grade 3–5 AEs. We used a random‐effects model to generate pooled estimates for proportions. Meta‐analyses using pooled risk ratios were performed for binary outcomes from comparative studies with the random effects model. Results A total of 13 eligible studies met our eligibility criteria, including 7673 patients. In the ICI‐chemotherapy combination subgroup, we observed that anti‐PD1 therapy was associated with better OS (p = 0.022) and PFS (p = 0.029) compared with anti‐PD‐L1 therapy. In the monotherapy subgroup, there was no statistical difference between the use of anti‐PD‐1 and anti‐PD‐L1 for OS and PFS. With regard to ORR and toxicity, in the ICI‐chemotherapy combination subgroup, we observed a trend of better ORR (p = 0.12) with the use of anti‐PD1 therapy and less frequent grade 3–5 AEs compared to the use of anti‐PD‐L1 therapy (p = 0.0302). In the monotherapy subgroup, there was no statistical difference between the use of anti‐PD‐1 and anti‐PD‐L1 regarding ORR and toxicity. Conclusions Our study suggests that PD‐1 drug plus chemotherapy is superior to anti‐PD‐L1 plus chemotherapy for NSCLC; nevertheless, as monotherapy, both strategies appear to be similar.

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Section: Discussionmentioning

confidence: 99%

Anti‐PD1 versus anti‐PD‐L1 immunotherapy in first‐line therapy for advanced non‐small cell lung cancer: A systematic review and meta‐analysis

2021

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“…The mechanism by which some patients who experience progression after initial immunotherapy may benefit from subsequent immunotherapy is still unclear. One reason for this may rely on differences between PD-1/PD-L1 inhibitors (28). And it may take time for the immune system to activate.…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy beyond progression in patients with advanced non-small cell lung cancer

Zhang²,

Zhang³

et al. 2020

Transl Lung Cancer Res

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Background: Immune checkpoint inhibitors (ICIs) represent a great breakthrough in the treatment of advanced non-small cell lung cancer (aNSCLC). However, whether immunotherapy beyond progression (IBP) is effective for aNSCLC has yet to be established. Therefore, a retrospective clinical study was conducted to investigate the efficacy of IBP in patients with aNSCLC under real-world conditions.Methods: A total of 125 Chinese patients with aNSCLC who experienced progressive disease (PD) after receiving monotherapy or combination therapy (combined with chemotherapy or/and antiangiogenic therapy) with programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors between January 2015 and March 2019 were enrolled. Patients who were treated with ICIs for more than 6 weeks after PD were defined as IBP (n=39), while those who received ICI treatment for less than 6 weeks or discontinued it due to PD were defined as non-IBP (n=86). Patient clinical characteristics were evaluated.An optimization-based method was applied to balance the clinical baseline characteristics between the two groups.Results: In total population, the IBP group had longer overall survival (median OS, 26.6 vs. 9.5 months; HR, 0.40; 95% CI: 0.23-0.69; P<0.001) and progression-free survival (median PFS, 8.9 vs. 4.1 months; HR, 0.41; 95% CI: 0.26-0.65; P<0.001), compared with the non-IBP group. Despite no significant difference in objective response rate (ORR, 15.4% vs. 11.6%, P=0.560), disease control rate (DCR) was significantly higher in the IBP group (89.7% vs. 61.6%, P<0.001). After balancing baseline covariates, the IBP group also had longer OS (median: 26.6 vs. 10.7 months; HR, 0.40; 95% CI: 0.19-0.84; P=0.015) and PFS (median: 9.7 vs. 4.3 months; HR, 0.28; 95% CI: 0.15-0.51; P<0.001), with a benefit in either of patients previously treated with ICI monotherapy or in combination therapy and with non-response to the previously ICI.Conclusions: IBP is associated with longer OS and PFS in patients with aNSCLC. Our findings may suggest new therapeutic options for patients with aNSCLC who experienced disease progression after initial immunotherapy.

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“…In contrast, in the KEYNOTE 045 study, a significant difference in OS was observed in favour of the anti-PD-1 pembrolizumab versus chemotherapy in patients with high PD-L1 tumours defined as CPS according the 22C3 Dako assay [ 57 ]. Although possible differences in efficacy between the anti-PD1 and anti-PD-L1 agents cannot completely be ruled out [ 58 ], plausible explanations may rely on the different tests and scores used to assess the PD-L1 expression, as well as on the tumoural site and timing of the biopsy in respect to the disease history. In this regard, it is noteworthy that the mOS duration in the high PD-L1 subgroup of patients differed between those two trials despite the similar populations enrolled and the mOS observed in the overall population of the chemotherapy control arm (of 8.4 and 7.3 months, for the IMvigor211 and the Keynote-045 study, respectively) [ 56 , 57 ].…”

Section: Molecular Factorsmentioning

confidence: 99%

Prognostic and Predictive Factors in Advanced Urothelial Carcinoma Treated with Immune Checkpoint Inhibitors: A Review of the Current Evidence

Rebuzzi

Banna

Murianni

et al. 2021

Cancers

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In recent years, the treatment landscape of urothelial carcinoma has significantly changed due to the introduction of immune checkpoint inhibitors (ICIs), which are the standard of care for second-line treatment and first-line platinum-ineligible patients with advanced disease. Despite the overall survival improvement, only a minority of patients benefit from this immunotherapy. Therefore, there is an unmet need to identify prognostic and predictive biomarkers or models to select patients who will benefit from ICIs, especially in view of novel therapeutic agents. This review describes the prognostic and predictive role, and clinical readiness, of clinical and tumour factors, including new molecular classes, tumour mutational burden, mutational signatures, circulating tumour DNA, programmed death-ligand 1, inflammatory indices and clinical characteristics for patients with urothelial cancer treated with ICIs. A classification of these factors according to the levels of evidence and grades of recommendation currently indicates both a prognostic and predictive value for ctDNA and a prognostic relevance only for concomitant medications and patients’ characteristics.

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Are anti-PD1 and anti-PD-L1 alike? The non-small-cell lung cancer paradigm

Cited by 43 publications

References 60 publications

Anti‐PD1 versus anti‐PD‐L1 immunotherapy in first‐line therapy for advanced non‐small cell lung cancer: A systematic review and meta‐analysis

Anti‐PD1 versus anti‐PD‐L1 immunotherapy in first‐line therapy for advanced non‐small cell lung cancer: A systematic review and meta‐analysis

Immunotherapy beyond progression in patients with advanced non-small cell lung cancer

Prognostic and Predictive Factors in Advanced Urothelial Carcinoma Treated with Immune Checkpoint Inhibitors: A Review of the Current Evidence

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