CONFERENCE UPDATE: ESMO 2023

Survival benefits of neoadjuvant nivolumab chemotherapy combination in patients with resectable NSCLC regardless of PD-L1 expression maintained in 3-year exploratory analysis from the CheckMate 816 trial

ONCOLOGY
29 Dec 2023

STUDY DESIGN

Results from the phase 3 CheckMate 816 study had found that neoadjuvant nivolumab plus chemotherapy (CTx) induced clinically significant and sustained benefits in the event-free survival (EFS) and overall survival (OS) of patients with resectable non-small cell lung cancer (NSCLC) compared to CTx-only.1 An exploratory subgroup analysis at 3 years was conducted to investigate the efficacy and safety outcomes of this combined neoadjuvant treatment among NSCLC patients by tumor programmed death-ligand 1 (PD-L1) expression (≥1% or <1%).1

During the phase 3 CheckMate 816 Study, adult patients with stage IB–III resectable NSCLC were randomized 1:1 to receive 360mg of nivolumab plus CTx once every 3 weeks or CTx only once every 3 weeks for 3 cycles.1 Both treatment groups consisted of similar proportions of patients with a tumor PD-L1 expression of ≥1% (nivolumab + CTx=89, CTx=89) and <1% (nivolumab + CTx=78, CTx=77).1

The endpoints of this exploratory analysis included event-free survival (EFS), overall survival (OS), pathologic complete response (pCR), major pathological response (MPR), surgical outcomes, and safety in patients with tumor PD-L1 ≥ 1% or < 1%.1 The minimum and median follow-ups were 32.9 months and 41.1 months, respectively.

Exploratory endpoints:
  • Selected endpoints were stratified by tumor PD-L1 expression and included EFS, OS, pCR, and surgical outcomes
  • Nivolumab + CTx exhibited a 63% risk-reduction in all-cause mortality (HR=0.37; 95% CI: 0.20-0.71) in patients with PD-L1 expression ≥1% compared with patients who received CTx only1
  • They also had a 54% risk-reduction in encountering negative disease events (HR=0.46; 95% CI: 0.28-0.77) and a higher pCR rate (difference=30.3%; 95% CI: 19.9-40.7) over the CTx only cohort1
  • When further targeting PD-L1 positive patients with stage II-IIIA disease, the addition of nivolumab retained favorable survival outcomes over the CTx only cohort (HR=0.43; 95% CI: 0.22-0.83)
  • In this population, the pCR (difference=29.8%; 95% CI: 19.0-40.7) and EFS (HR=0.49; 95% CI:0.29-0.83) results were also favorable1
  • The benefits of adding nivolumab was less pronounced in patients with tumor PD-L1 <1%, with only a 19% risk reduction in all-cause mortality (HR=0.81; 95% CI: 0.48-1.36)1
  • Similarly, the difference in pCR rate (14.1%; 95% CI: 4.8-24.0) and the risk-reduction in encountering negative disease events (HR=0.87; 95% CI: 0.57-1.35) were also less prominent in this population1
  • Patients who achieved pCR (n=43) had improved EFS (HR=0.15; 95% CI: 0.06-0.37) and OS (HR=0.12; 95% CI: 0.03-0.50) compared to those who did not (n=136) in the nivolumab + CTx cohort1
  • A numerically higher proportion of patients in the nivolumab + CTx cohort received lobectomy instead of pneumonectomy, regardless of their tumor PD-L1 expression (PD-L1 ≥1%: 79% vs. 17%, PD-L1 <1%: 81% vs. 11%)1
Safety:
  • Neoadjuvant nivolumab + CTx was found to be well-tolerated among patients, with a numerically higher rate of patients successfully undergoing definitive surgery compared to CTx alone, regardless of tumor PD-L1 expression (tumor PD-L1 ≥ 1%: 84% vs.74%; tumor PD-L1 <1%: 81% vs. 77%)1

 

“Results of this exploratory analysis reinforce the role of nivolumab plus chemotherapy as a standard neoadjuvant treatment for patients with resectable NSCLC, regardless of tumor PD-L1 expression.”

Dr. Mariano Provencio Pulla
Medical Oncology Department,
Puerta de Hierro University Hospital
Madrid, Spain

Get access to our exclusive articles.
Related Articles

First-line osimertinib + CT reduces risk of disease progression and death among EGFRm NSCLC patients with CNS metastases: Exploratory analysis of the FLAURA2 study

The phase 2 FLAURA2 study found that first-line combination of osimertinib and chemotherapy (CT) offered significant survival benefits among patients who were diagnosed with epidermal growth factor receptor-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC) compared to first-l
ONCOLOGY
02 Jan 2024

Enfortumab vedotin plus pembrolizumab significantly improves outcomes compared to chemotherapy in patients with previously untreated locally advanced metastatic urothelial carcinoma: The EV-302/KEYNOTE-A39 study

While platinum-based chemotherapy (CTx) has been the standard first-line (1L) treatment for locally advanced metastatic urothelial carcinoma (la/mUC) for decades, many patients continue to experience disease progression after treatment, resulting in poor prognosis and low 5-year surviv
ONCOLOGY
29 Dec 2023

Association of AL with neurological effects in the pediatric population

A retrospective study on a pediatric population has shown that neurologic manifestations (NMs) in patients with acute leukemia (AL), relating to a greater mortality rate.1 AL is the most prevalent childhood cancer, which accounts for one-third of all cancers within the age range.1 Although the survi
PEDIATRICS NEUROLOGY ...
28 Feb 2023

Favorability of sequential conditioning over intensive remission induction chemotherapy prior to allo-HCT

In the 64th American Society of Hematology (ASH) Annual Meeting and Exposition 2022, Dr. Johannes Schetelig, on behalf of the Study Alliance Leukemia and the German Cooperative Transplant Study Group, presented his group’s study to prove their hypothesis that salvage chemotherapy before allogeneic h
HEMATOLOGY
23 Feb 2023

Adjuvant nivolumab shows effectiveness in reducing recurrence and death in patients with stage IIB/C melanoma

Data from the phase 3 CheckMate-76K trial found that adjuvant nivolumab was effective in improving recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) among patients with completely resected stage IIB/C melanoma.1 These findings supported the use of nivolumab in adjuvant setting to prevent disease recurrence of stage IIB/C melanoma.1
ONCOLOGY
31 Oct 2022

Administration of ANTI-PD1 antibody pembrolizumab improves EFS in tnbc patients

Among different subtypes of breast cancer, triple-negative breast cancer (TNBC) is associated with the least overall survival (OS).1 The use of immune checkpoint inhibitors, such as programmed death 1 (PD1) or programmed death-ligand 1 (PD-L1), benefits TNBC patients.1 An interim analysis of a phase 3 trial revealed that administration of pembrolizumab, an immune checkpoint inhibitor, along with neoadjuvant chemotherapy, resulted in a pathological complete response in a significant number of patients with high-risk early TNBC.1
ONCOLOGY OBSTETRICS & GYNECOLOGY
02 May 2022

Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab shows efficacy for early-stage TNBC: KEYNOTE-522 phase 3 trial
ONCOLOGY OBSTETRICS & GYNECOLOGY
04 Oct 2021

Osimertinib significantly improved disease-free survival in patients with resected EGFR-mutated non-small cell lung cancer, regardless of adjuvant chemotherapy use
ONCOLOGY RESPIROLOGY
27 Feb 2021

The first ever phase 3, placebo-controlled study of nivolumab in relapsed malignant mesothelioma CONFIRMed its survival benefits
ONCOLOGY
27 Feb 2021

Frontline pembrolizumab plus chemotherapy significantly improves survival compared with chemotherapy alone in patients with locally advanced unresectable or metastatic esophageal cancer
ONCOLOGY
30 Dec 2020