Pembrolizumab (pembro) + chemotherapy (chemo) in metastatic squamous NSCLC: Final analysis and progression after the next line of therapy (PFS2) in KEYNOTE-407

Paz-Ares, L.; Vicente, David; Tafreshi, Ali; Robinson, Andrew; Parra, H. Soto; Hermes, Bárbara; Çiçin, İrfan; Medgyasszay, Balazs; Barry, B.; Cid, Jerónimo Rodríguez; Okamoto, Isamu; Lee, S.; Vladimirov, Vladimir; Cheng, Ying; Baş, Tolga; Piperdi, Bilal; Halmos, Balázs

doi:10.1093/annonc/mdz394.080

Cited by 17 publications

(20 citation statements)

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“…In phase II exploratory study NADIM, neoadjuvant triplets of carboplatin, paclitaxel, and nivolumab yielded a striking pCR rate of 69.2% and an overall response (MPR þ pCR) rate of 84.6% [29]. The results of phase III studies Keynote-189 and Keynote-407 further suggested superiority of pembrolizumab plus chemotherapy in the first-line treatment of NSCLC [30,31]. Those studies exhibit reference value to the application of neoadjuvant ICIs in gastrointestinal tumors.…”

Section: Discussionmentioning

confidence: 92%

Efficacy and safety of neoadjuvant immunotherapy in patients with microsatellite instability-high gastrointestinal malignancies: A case series

Zhang

Cheng

Gong

et al. 2020

European Journal of Surgical Oncology

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Introduction: Immune checkpoint inhibitors (ICIs) have been approved for the late-line treatment of unresectable gastrointestinal tumors, but their efficacy and safety in the neoadjuvant setting have not been described. Whether dMMR/MSI-H populations benefit from preoperative ICIs plus surgery remains undefined. Materials and methods: Six consecutive patients managed at our institution received neoadjuvant ICIs and surgery for advanced, resectable, and MSI-H gastrointestinal tumors. All patients underwent thorough clinical evaluations and radiographic investigations before and during treatment. Next-generation sequencing (NGS), immunohistochemical (IHC) staining, and in situ hybridization (ISH) were also performed for each patient' s biopsy section to generate their molecular profiling. Results: Neoadjuvant immunotherapy was efficient and well-tolerated in patients with dMMR/MSI-H gastrointestinal tumors. Pathologic responses were observed in 6/6 (100%) dMMR/MSI-H tumors, with 5/6 (83%) complete responses. The other patient was also confirmed to demonstrate a TNM downstaging after treated with ICIs. Three patients (50%) developed grade I/II adverse events. All enrolled patients underwent timely operations without the occurrence of unexpected perioperative or postoperative complications. No disease recurrence was identified during the follow-up so far. Conclusions: Neoadjuvant immunotherapy results in favorable pathologic responses and minor adverse effects among patients with MSI-H gastrointestinal tumors. This pre-operative measure does not compromise subsequent surgery. There is an urgent need to warrant large-cohort clinical trials to examine the utility of neoadjuvant ICIs in resectable, dMMR/MSI-H gastrointestinal malignancies.

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Section: Discussionmentioning

confidence: 92%

Efficacy and safety of neoadjuvant immunotherapy in patients with microsatellite instability-high gastrointestinal malignancies: A case series

Zhang

Cheng

Gong

et al. 2020

European Journal of Surgical Oncology

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“…Many studies on various tumor types including NSCLC could show that not women but men have an increased efficacy of single agent ICI treatment [ 4 , 26 , 75 , 76 ]. On the other hand, women apparently have a greater advantage from a combination of ICI and chemotherapy [ 8 , 12 , 21 , 27 , 60 ]. A possible hypothesis to explain this finding could be that the immune responses of women tend to be stronger, which means that a woman’s lung cancer requires more effective mechanisms to escape the immune system and is therefore less immunogenic than a comparable tumor in a male patient and therefore more resistant to immunotherapy [ 26 , 77 ].…”

Section: Main Textmentioning

confidence: 99%

“…Conversely, tTMB was not associated with outcomes in the chemotherapy-arm in either study. In contrast, no association between tTMB levels and efficacy in neither RR, PFS nor OS of pembrolizumab and/or chemotherapy were found in the KEYNOTE-021, − 189 or 407 studies [ 60 ]. Therefore, tTMB is not established as a marker for ICI efficacy in NSCLC so far.…”

Section: Main Textmentioning

confidence: 99%

Clinically relevant prognostic and predictive markers for immune-checkpoint-inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC)

2020

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Background Immune checkpoint inhibitors (ICI) either alone or in combination with chemotherapy have expanded our choice of agents for the palliative treatment of non-small cell lung cancer (NSCLC) patients. Unfortunately, not all patients will experience favorable response to treatment with ICI and may even suffer from severe side effects. Therefore, prognostic and predictive markers, beyond programmed death ligand 1 (PD-L1) expression status, are of utmost importance for decision making in the palliative treatment. This review focuses on clinical, laboratory and genetic markers, most of them easily to obtain in the daily clinical practice. Results Recently, a number of prognostic and predictive factors in association to palliative ICI therapy have been described in NSCLC. Besides biometric parameters and clinical characteristics of the tumor, there are useful markers from routine blood sampling as well as innovative soluble genetic markers which can be determined before and during ICI treatment. Additionally, the level of evidence is noted. Conclusions These factors can be helpful to predict patients’ outcome and tumor response to ICI. They should be implemented prospectively in ICI based clinical trials to develop reliable algorithms for palliative NSCLC treatment.

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“…The final analysis was released in June 2020, which once again demonstrated that the experimental arm of pembrolizumab combined chemotherapy significantly extended OS and PFS (OS: 17.1 months versus 11.6 months; PFS: 8.0 months versus 5.1 months) ( Paz-Ares et al., 2020 ). Moreover, the results of the KEYNOTE-189 were updated at the European Society of Medical Oncology (ESMO) meeting in 2019, where the patients treated with pembrolizumab combined with chemotherapy were shown to have increased ORR and longer PFS and OS ( Paz-Ares et al., 2019 ). Furthermore, the administration of pembrolizumab combinatorial therapy reduced the risk of death in the patients by 29%, indicating its safety.…”

Section: First-line Immune-checkpoint Inhibitors Therapy Combined Witmentioning

confidence: 99%

First-Line Immune-Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Current Landscape and Future Progress

Huang

Lü

et al. 2020

Front. Pharmacol.

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Lung cancer is one of the most common cancers and the leading cause of cancer-related deaths worldwide. Most of these patients with non-small cell lung cancer (NSCLC) present with the advanced stage of the disease at the time of diagnosis, and thus decrease the 5-year survival rate to about 5%. Immune checkpoint inhibitors (ICIs) can act on the inhibitory pathway of cancer immune response, thereby restoring and maintaining anti-tumor immunity. There are already ICIs targeting different pathways, including the programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) pathway. Since March 2015, the US Food and Drug Administration (FDA) approved nivolumab (anti-PD-1 antibody) as the second-line option for treatment of patients with advanced squamous NSCLC. Additionally, a series of inhibitors related to PD-1/PD-L1 immune-checkpoints have helped in the immunotherapy of NSCLC patients, and modified the original treatment model. However, controversies remain regarding the use of ICIs in a subgroup with targeted oncogene mutations is a problem that we need to solve. On the other hand, there are continuous efforts to find biomarkers that effectively predict the response of ICIs to screen suitable populations. In this review, we have reviewed the history of the continuous developments in cancer immunotherapy, summarized the mechanism of action of the immune-checkpoint pathways. Finally, based on the results of the first-line recent trials, we propose a potential first-line immunotherapeutic strategy for the treatment of the patients with NSCLC.

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Pembrolizumab (pembro) + chemotherapy (chemo) in metastatic squamous NSCLC: Final analysis and progression after the next line of therapy (PFS2) in KEYNOTE-407

Cited by 17 publications

References 0 publications

Efficacy and safety of neoadjuvant immunotherapy in patients with microsatellite instability-high gastrointestinal malignancies: A case series

Efficacy and safety of neoadjuvant immunotherapy in patients with microsatellite instability-high gastrointestinal malignancies: A case series

Clinically relevant prognostic and predictive markers for immune-checkpoint-inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC)

First-Line Immune-Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Current Landscape and Future Progress

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