Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial

Cascone, Tina; William, William N.; Weissferdt, Annikka; Leung, Cheuk Hong; Lin, Heather; Pataer, Apar; Godoy, Myrna C.B.; Carter, Brett W.; Federico, Lorenzo; Reuben, Alexandre; Khan, Abdul Wadud; Dejima, Hitoshi; Francisco‐Cruz, Alejandro; Parra, Edwin R.; Solis, Luisa M.; Fujimoto, Junya; Tran, Hai T.; Kalhor, Neda; Fossella, Frank V.; Mott, Frank E.; Tsao, Anne S.; Blumenschein, George; Le, Xiuning; Zhang, Jianjun; Skoulidis, Ferdinandos; Kurie, Jonathan M.; Altan, Mehmet; Lu, Charles; Glisson, Bonnie S.; Byers, Lauren A.; Elamin, Yasir Y.; Mehran, Reza J.; Rice, David C.; Walsh, Garrett L.; Hofstetter, Wayne L.; Roth, Jack A.; Antonoff, Mara B.; Kadara, Humam; Haymaker, Cara; Bernatchez, Chantale; Ajami, Nadim J.; Jenq, Robert R.; Sharma, Padmanee; Allison, James P.; Futreal, Andrew; Wargo, Jennifer A.; Wistuba, Ignacio I.; Swisher, Stephen G.; Lee, John; Gibbons, Don L.; Vaporciyan, Ara A.; Sepesi, Boris

doi:10.1038/s41591-020-01224-2

Cited by 434 publications

(484 citation statements)

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“…LCMC3 examined the impact of two cycles of neoadjuvant atezolizumab on MPR in stage IB-selected IIIB NSCLC patients and is the largest trial in lung immune-related TRAE were reported, including a case of grade 5 pneumonitis, which was seen in a patient treated with nivolumab alone. 47 There was no apparent increase in toxicity, but more CD3+ T cell infiltration, CD8+ tissue resident and CD4+ effector memory T cells at surgery, and potentially greater induction of peripheral T-cell clonality and increased repertoire with neoadjuvant NI as compared with N; these findings once again recapitulate those shown in preclinical models. At a median follow-up of 22 months, median recurrence-free survival and OS has not been reached in either cohort.…”

Section: Neoadjuvant Immunotherapy Trials In Nsclcsupporting

confidence: 59%

“…46 NEOSTAR assessed the rate of MPR in patients treated with three neoadjuvant cycles of nivolumab alone (N) or nivolumab plus one dose of ipilimumab with the first nivolumab cycle (NI). 47 Forty-four patients with stage I-IIIA (single N2 positive node) NSCLC were recruited (N=23, NI=21) and the outcome of 44 randomized patients was reported. Overall, 37 patients had surgery and of those, MPR rate was 29% (N 22%, NI 38%).…”

Section: Neoadjuvant Immunotherapy Trials In Nsclcmentioning

confidence: 99%

“…At a median follow-up of 22 months, median recurrence-free survival and OS has not been reached in either cohort. 47 …”

Section: Neoadjuvant Immunotherapy Trials In Nsclcmentioning

confidence: 99%

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Neoadjuvant immunotherapy for non-small cell lung cancer: right drugs, right patient, right time?

Ahern

Solomon

Hui

et al. 2021

J Immunother Cancer

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Standard curative treatment of early-stage non-small cell lung cancer (NSCLC) involves surgery in combination with postoperative (adjuvant) platinum-based chemotherapy where indicated. Preoperative (neoadjuvant) therapies offer certain theoretical benefits compared with adjuvant approaches, including the ability to assess on-treatment response, reduce the tumor bulk prior to surgery, and enhance tolerability in the preoperative setting. Indeed, the use of neoadjuvant therapies are well established in other cancers such as breast and rectal cancers to debulk the tumor and guide ongoing therapy, and neoadjuvant chemotherapy has similar efficacy but less toxicity in NSCLC. More recently, immune checkpoint inhibitors (ICI) targeting programmed death-1 (PD1)/PD1-ligand 1 (PD-L1) have transformed the treatment of advanced NSCLC; the unique mechanisms of action of ICI offer additional rationale for assessment in the neoadjuvant setting. Preclinical studies in mouse cancer models support the proof of concept of neoadjuvant ICI (NAICI) through improvement of T-cell effector function and long-term memory induction. Preliminary early-phase human trial data support the proposition that NAICI in NSCLC may provide an feasible and potentially efficacious future treatment strategy and large, randomized phase III trials are currently recruiting to assess this approach. However, outstanding issues include defining optimal treatment combinations which balance high efficacy with acceptable toxicity, validating biomarkers to aid in patient selection, and avoiding potential pitfalls such as missing a window for successful surgery, that is, choosing the right drugs, for the right patient, at the right time. Predictive biomarkers to direct selection of therapy are required, and the validation of major pathological response (MPR) as a surrogate for survival will be important in the uptake of the neoadjuvant approach.

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Section: Neoadjuvant Immunotherapy Trials In Nsclcsupporting

confidence: 59%

Section: Neoadjuvant Immunotherapy Trials In Nsclcmentioning

confidence: 99%

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Neoadjuvant immunotherapy for non-small cell lung cancer: right drugs, right patient, right time?

Ahern

Solomon

Hui

et al. 2021

J Immunother Cancer

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“…Interim efficacy results from nivolumab (3 mg/kg days 1, 15, 29) and nivolumab plus ipilimumab (1 mg/kg day 1) cohorts have been reported. 21 A total of 44 patients were randomized, 23 receiving nivolumab and 21 receiving nivolumab plus ipilimumab. Of the 37 patients who underwent tumor resection, MPR rate was 35% (24% for nivolumab and 50% for nivolumab plus ipilimumab).…”

Section: Neoadjuvant Immunotherapy In Resectable Nsclc – Review Of the Datamentioning

confidence: 99%

Neoadjuvant and Adjuvant Immunotherapy in Early-Stage Non-Small Cell Lung Cancer

Shukla

Hanna

2021

LCTT

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Surgery or concurrent chemoradiation are standard of care treatments for patients with localized and locally advanced non-small cell lung cancer (NSCLC). While resection and chemoradiation are potentially curative therapies for early-stage disease, relapse rates remain high. Adjuvant or neoadjuvant chemotherapy improves cure rates 5–15% compared with surgery alone for patients with resectable disease. Immune checkpoint inhibitors (ICI) have heralded a new era for the treatment of advanced NSCLC with one-third of patients experiencing long-term survival. There is increasing interest in examining the role of ICI therapy in patients with early-stage NSCLC. Consolidation durvalumab after chemoradiation has become a part of standard of care for patients with inoperable, locally advanced disease. More recently, there is emerging evidence that neoadjuvant treatment with ICIs results in substantial rates of major pathologic response and pathologic complete response, and high rates of R0 resection with no significant delay in time to surgery. Furthermore, preliminary data show that adjuvant treatment with ICIs after adjuvant chemotherapy improves disease-free survival and may play a critical role in reducing disease recurrence in patients with resectable disease. In this review, we discuss recently reported and ongoing studies that are designed to define the role of immunotherapy in patients with non-metastatic NSCLC.

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“…5,6 Recently, immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have demonstrated remarkable efficacy in the management of advanced and metastatic NSCLC leading to their incorporation in standard treatment regiments. 7 This has led to great enthusiasm for potential benefit in resectable disease, and multiple trials were launched exploring the role of ICIs in early-stage NSCLC, with promising early results.…”

mentioning

confidence: 99%

Commentary: A new hope—neoadjuvant immunotherapy for resectable non–small cell lung cancer

Fernández

Ahmad

2022

The Journal of Thoracic and Cardiovascular Surgery

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Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial

Cited by 434 publications

References 44 publications

Neoadjuvant immunotherapy for non-small cell lung cancer: right drugs, right patient, right time?

Neoadjuvant immunotherapy for non-small cell lung cancer: right drugs, right patient, right time?

Neoadjuvant and Adjuvant Immunotherapy in Early-Stage Non-Small Cell Lung Cancer

Commentary: A new hope—neoadjuvant immunotherapy for resectable non–small cell lung cancer

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