CheckMate 592: A phase II exploratory study of biomarkers associated with the efficacy of first-line nivolumab (nivo) plus ipilimumab (ipi) in patients (pts) with stage IV or recurrent NSCLC

Gettinger, Scott; Beck, Thaddeus; Yang, Xinyun; Telivala, Bijoy; Morgensztern, Daniel; Velcheti, Vamsidhar; Ramalingam, Suresh S.; Schalper, Kurt A.; Dajee, Maya; Ranck, A.; Yang, Rong; Spigel, David R.

doi:10.1093/annonc/mdy292.124

Cited by 3 publications

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“…In NSCLC, preliminary results support this potential predictive role for TMB [ 38 , 42 ], but more evidence is needed. Thus, several clinical trials have assessed the predictive value of TMB in different studies with combined ICI regimens, such as nivolumab plus ipilimumab [ 43 , 44 , 45 , 46 ], or ICI monotherapy, such as with atezolizumab [ 47 , 48 , 49 ] and pembrolizumab [ 50 ].…”

Section: Introductionmentioning

confidence: 99%

PD-(L)1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer Patients with High PD-L1 Expression: A Network Meta-Analysis

Majem

Cobo-Dols

Isla

et al. 2021

JCM

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Programmed cell death-ligand 1 (PD-L1) has emerged as a potential biomarker for selection of patients more likely to respond to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC). In this network meta-analysis, we aimed to evaluate the efficacy of first-line anti-PD-(L)1 monotherapy in advanced NSCLC patients with high PD-L1 expression (≥50%) compared to platinum-based chemotherapy. We also evaluated efficacy outcomes according to tumor mutational burden (TMB). To that end, we conducted a systematic review. Six clinical trials with 2111 patients were included. In head-to-head comparisons, immunotherapy showed a significant improvement in progression-free survival (PFS: HRpooled = 0.69, 95% CI: 0.52–0.90, p = 0.007), overall survival (OS: HRpooled = 0.69, 95% CI: 0.61–0.78; p < 0.001) and overall response rate (ORR) (Risk ratio (RR)pooled = 1.354, 95% CI: 1.04–1.762, p = 0.024). In the assessment of relative efficacy for PFS through indirect comparisons, pembrolizumab (results from KEYNOTE-024) ranked highest followed by cemiplimab and atezolizumab, with statistical significance determined for some of the drugs. In terms of OS, cemiplimab ranked highest followed by atezolizumab and pembrolizumab, although non-significant OS was determined for these drugs. In conclusion, PD-(L)1 inhibitor monotherapy improves efficacy outcomes in the first line setting of advanced NSCLC patients with high PD-L1 expression. Evaluations with longer follow up are still needed to determine the superiority of any specific drug.

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Section: Introductionmentioning

confidence: 99%

PD-(L)1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer Patients with High PD-L1 Expression: A Network Meta-Analysis

Majem

Cobo-Dols

Isla

et al. 2021

JCM

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“…The primary endpoint in part 1 is the association of response rate (RR) with baseline TMB, along with candidate peripheral blood and tumor biomarkers at baseline and on treatment; as well as outcome according to progression-free survival (PFS) and overall survival (OS). Primary endpoints in part 2 are the association of RR with baseline tissue and blood TMB, and secondary endpoints are RR, PFS, OS, safety, and the association of enteric biomarkers with efficacy 45. This trial will help to elucidate other potential predictive biomarkers with clinical utility in daily clinical practice for patient selection.…”

Section: Tumor Mutational Burden and Other Biomarkersmentioning

confidence: 99%

<p>Nivolumab plus ipilimumab combination therapy for the first-line treatment NSCLC: evidence to date</p>

Remón

Esteller

Taus

2019

CMAR

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Immune checkpoint inhibitors (ICI) as monotherapy in selected patients as well as in combination with chemotherapy have become the standard of care in the first-line treatment strategy of advanced non-small cell lung cancer (NSCLC) patients. Combination treatment with ICI, such as nivolumab and ipilimumab or durvaluamb and ipilimumab, has also been proposed as potential strategies in this setting in selected advanced NSCLC patients. Characterizing predictive markers of long-term clinical benefit with ICI is a critical objective. Tumor mutational burden has been proposed as a potential predictive biomarker. In this review, we discuss the efficacy of nivolumab and ipilimumab in advanced NSCLC patients as well as the clinical utility of tumor mutational burden in the efficacy of this combination. Ongoing clinical trials with nivolumab and ipilimumab, and the efficacy of this combination in subgroups of NSCLC patients, such as elderly patients and patients with brain metastases, are also discussed.

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“…In NSCLC, preliminary results support this potential predictive role for TMB [38,42], but more evidence is needed. Thus, several clinical trials have assessed the predictive value of TMB in different studies with combined ICI regimens, such as nivolumab plus ipilimumab [43][44][45][46], or ICI monotherapy, such as with atezolizumab [47][48][49] and pembrolizumab [50].…”

Section: Introductionmentioning

confidence: 99%

PD-(L)1 inhibitors as monotherapy for the first-line treatment of non-small cell lung cancer patients with high PD-L1 expression: A network meta-analysis.

Majem

Cobo

Isla

et al. 2021

JCO

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9076 Background: PD-L1 has emerged as a potential biomarker for predicting responses to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC). In this network meta-analysis, we aimed to evaluate the efficacy of first-line PD-(L)1 monotherapy in advanced NSCLC patients with high PD-L1 expression. Methods: We conducted a systematic search in PubMed to identify all eligible trials from inception until 1 November 2020, with no start date limit applied. Only phase III trials evaluating the efficacy of first-line (1L) PD-(L)1 monotherapy in patients with stage IIIB/stage IV NSCLC and high PD-L1 expression were included. Results: Six clinical trials (KEYNOTE-024, KEYNOTE-042, EMPOWER Lung-01, IMpower110, MYSTIC and CheckMate-026) with 2,111 patients were included. In head-to-head comparisons, immunotherapy showed a significant improvement in progression-free survival (PFS: HRpooled = 0.69, 95% CI: 0.52-0.90, p = 0.007), overall survival (OS: HRpooled = 0.69, 95% CI: 0.61-0.78; p < 0.001) and overall response rate (ORR) (Risk ratio [RR]pooled = 1.354, 95% CI: 1.04-1.762, p = 0.024) compared to chemotherapy (CT). In the assessment of relative efficacy for PFS through indirect comparisons, pembrolizumab (results from KEYNOTE-024) ranked highest followed by cemiplimab and atezolizumab, with statistical significance determined across some of the drugs. In terms of OS, cemiplimab ranked highest followed by atezolizumab and pembrolizumab, although non-significant OS was determined across these drugs. Overall, 1L PD-(L)1 monotherapy improved OS in almost all subgroups, reaching statistical significance in men (HRpooled = 0.624, 95% CI: 0.51-0.72, p < 0.001), non-Asian patients (HRpooled = 0.66, 95% CI: 0.55-0.79, p < 0.001), all patients regardless of age ( < 65 years [HRpooled = 0.72, 95% CI: 0.57-0.90, p = 0.005]; ≥65 years [HRpooled = 0.61, 95% CI: 0.48-0.77, p < 0.001]), ECOG PS status (ECOG PS = 0 [HRpooled = 0.68, 95% CI: 0.56-0.82, p < 0.001; ECOG PS = 1 [HRpooled = 0.59, 95% CI: 0.43-0.82, p = 0.001) and histological tumour type (Squamous [HRpooled = 0.49, 95% CI: 0.37-0.67, p < 0.001; Non-squamous [HRpooled = 0.67, 95% CI: 0.52-0.87, p = 0.003). In the case of smokers and NSCLC stage, only current/former smokers (HRpooled = 0.623, 95% CI: 0.47-0.83, p = 0.001) and patients with stage IV disease* (HRpooled = 0.687, 95% CI: 0.59-0.81, p < 0.001) benefited from single PD-(L)1 monotherapy over CT. Conclusions: PD-(L)1 inhibitor monotherapy improves efficacy outcomes in the 1L setting of advanced NSCLC patients with high PD-L1 expression. Current/former smokers ≥65 years, with ECOG PS = 1 and squamous NSCLC benefited most from this therapy. *KEYNOTE-042 was the only study including patients with stage IIIB NSCLC.

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CheckMate 592: A phase II exploratory study of biomarkers associated with the efficacy of first-line nivolumab (nivo) plus ipilimumab (ipi) in patients (pts) with stage IV or recurrent NSCLC

Cited by 3 publications

References 0 publications

PD-(L)1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer Patients with High PD-L1 Expression: A Network Meta-Analysis

PD-(L)1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer Patients with High PD-L1 Expression: A Network Meta-Analysis

<p>Nivolumab plus ipilimumab combination therapy for the first-line treatment NSCLC: evidence to date</p>

PD-(L)1 inhibitors as monotherapy for the first-line treatment of non-small cell lung cancer patients with high PD-L1 expression: A network meta-analysis.

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