Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB–IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial

O’Brien, Mary; Paz‐Ares, Luis; Marréaud, Sandrine; Dafni, Urania; Oselin, Kersti; Havel, Libor; Esteban, Emilio; Isla, Dolores; Martinez-Martí, Alex; Faehling, Martin; Tsuboi, Masahiro; Lee, Jong-Seok; Nakagawa, Kazuhiko; Yang, Jing; Samkari, Ayman; Keller, Steven M.; Mauer, Murielle; Jha, Nitish; Stahel, Rolf A.; Besse, Benjamin; Peters, Solange

doi:10.1016/s1470-2045(22)00518-6

Cited by 269 publications

(191 citation statements)

References 30 publications

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“…An exploratory subgroup analysis suggested that the DFS benefit may have been driven by the TPS PD-L1 1–49% group. The pembro safety profile was as expected; AEs were grade ≥ 3 in 34.1% of pts in the pembro arm vs. 25.8% in the placebo arm and led to discontinuation in 19.8% vs. 5.9%; treatment-related Aes led to death in 0.7% vs. 0% [ 66 ].…”

Section: Adjuvant Immunotherapymentioning

confidence: 64%

Moving Immune Checkpoint Inhibitors to Early Non-Small Cell Lung Cancer: A Narrative Review

Viscardi

Vitiello

Servetto

et al. 2022

Cancers

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Lung cancer is the leading cause of cancer-related death worldwide. Since prognosis of early-stage non-small cell lung cancer (NSCLC) remains dismal for common relapses after curative surgery, considerable efforts are currently focused on bringing immunotherapy into neoadjuvant and adjuvant settings. Previously, perioperative chemotherapy showed only a modest but significative improvement in overall survival. The presence of broad tumor neoantigens load at primary tumor prior to surgery as well as the known immunosuppressive status following resection represent the main rationale for immunotherapy in early disease. Several trials have been conducted in recent years, leading to atezolizumab and nivolumab approval in the adjuvant and neoadjuvant setting, respectively, and perioperative immunotherapy in NSCLC remains a field of active clinical and preclinical investigation. Unanswered questions in perioperative therapy in NSCLC include the optimal sequence and timing of chemotherapy and immunotherapy, the potential of combination strategies, the role of predictive biomarkers for patient selection and the choice of useful endpoints in clinical investigation.

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Section: Adjuvant Immunotherapymentioning

confidence: 64%

Moving Immune Checkpoint Inhibitors to Early Non-Small Cell Lung Cancer: A Narrative Review

Viscardi

Vitiello

Servetto

et al. 2022

Cancers

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“…ICIs have markedly changed the treatment of lung cancer, and their indications have expanded beyond advanced lung cancer to include adjuvant and neoadjuvant settings. 9 , 10 , 11 , 12 However, severe irAEs occur in rare cases, 1 even after the discontinuation of ICIs. 2 , 3 , 4 , 5 , 6 , 7 , 8 The late‐onset toxicity of ICI therapy has been attracting increasing attention.…”

Section: Discussionmentioning

confidence: 99%

Late‐onset acute type 1 diabetes mellitus 7 months after discontinuation of pembrolizumab against lung cancer

et al. 2022

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Immune‐related adverse events (irAEs) occur in rare cases, even after the completion of immune checkpoint inhibitor (ICI) therapy. We encountered a lung cancer patient diagnosed with acute‐onset type 1 diabetes mellitus (DM) 7 months after the cessation of ICI. A 68‐year‐old woman was referred to our hospital for chest abnormalities. She was diagnosed with lung adenocarcinoma cT4N2M1c, stage IVB. Immunostaining showed that the expression of programmed death ligand 1 in tumor cells was negative. A genetic analysis using the Oncomine Dx Target Test Multi‐CDx System revealed that the primary tumor was positive for ERBB2. Combined immunotherapy with carboplatin, pemetrexed, and pembrolizumab was performed as first‐line therapy, followed by maintenance therapy with pemetrexed plus pembrolizumab, which was successful. After the seventh course, maintenance therapy was stopped because only the primary tumor showed local enlargement. Local chest radiotherapy (66 Gy/33 Fr) was performed, and the patient was followed up. HbA1c was 4.9% 3 months after the completion of pembrolizumab, and dry mouth and polyuria occurred after 5 months. Seven months later, the patient developed diabetic ketoacidosis with a blood glucose of 348 mg/dL and an HbA1c of 11.3%. Antiglutamic acid decarboxylase antibodies were negative and urinary C‐peptide was 9.3 μg/day. The patient was diagnosed with acute‐onset type 1 diabetes and received insulin therapy. There has been no case report of type 1 diabetes diagnosed 7 months after the last administration of an ICI. These results indicate that irAE needs to be considered even after the cessation of ICI.

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“…On the other hand, the KEYNOTE-091 study results were seemingly contradictory. The results showed that DFS was significantly improved in patients receiving pembrolizumab in the allcomer population, regardless of PD-L1 expression, but PD-L1 TC ≥50% NSCLC patients did not exhibit a survival benefit (59,61). In conclusion, the predictive role of PD-L1 expression for adjuvant immunotherapy remains to be established.…”

Section: Biomarkers Predictive Of Benefit Of Adjuvant Immunotherapymentioning

confidence: 98%

Adjuvant immunotherapy in early-stage resectable non–small cell lung cancer: A new milestone

Tang

Ye²,

Tang³

et al. 2023

Front. Oncol.

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Currently, chemotherapy is the standard adjuvant treatment for early-stage non-small cell lung cancer (NSCLC). However, adjuvant cisplatin-based chemotherapy after surgery has been shown to improve 5-year survival rates by only 4−5%. Immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced NSCLC, there is a growing interest in the role of immunotherapy in early-stage NSCLC. Here, we summarize the rationale for adjuvant immunotherapy, including the postoperative immunosuppressive environment and immunological effects of platinum chemotherapy. Many ongoing clinical trials and the related progress in adjuvant immunotherapy in early-stage resectable NSCLC are discussed. Furthermore, we highlight several unresolved challenges, including markers predictive of treatment benefit, the efficacy of treatment for some oncogene-addicted tumors, the optimal combination therapy, the duration of adjuvant immunotherapy, and optimal selection between neoadjuvant and adjuvant immunotherapy. Early findings in some clinical trials are promising, and updated overall survival results will be useful for validating the current role of adjuvant immunotherapy, particularly in the context of perioperative strategy.

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Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB–IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial

Cited by 269 publications

References 30 publications

Moving Immune Checkpoint Inhibitors to Early Non-Small Cell Lung Cancer: A Narrative Review

Moving Immune Checkpoint Inhibitors to Early Non-Small Cell Lung Cancer: A Narrative Review

Late‐onset acute type 1 diabetes mellitus 7 months after discontinuation of pembrolizumab against lung cancer

Adjuvant immunotherapy in early-stage resectable non–small cell lung cancer: A new milestone

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