By Edgardo S. Santos Castillero, MD, FACP
Five abstracts were presented at the Presidential Symposium of the 2018 IASLC Latin America Conference on Lung Cancer, held in August in Córdoba, Argentina. All of the presentations centered on immunotherapy, with the following themes: (1) defining best treatment options as first-line therapy, (2) novel immunotherapy combinations, (3) novel biomarkers to assess immuneoncology response, and (4) possible differences among ethnic groups.
The KEYNOTE-024 trial featured prolonged follow-up (data cutoff July 10, 2017) and demonstrated that first-line pembrolizumab monotherapy remains superior to platinum-based chemotherapy in patients with greater than 50% PD-L1 expression, despite crossover from chemotherapy to an anti–PD-1 drug. The hazard ratio for overall survival (OS) was 0.63, 95% CI (0.47, 0.86).1
The authors of KEYNOTE-042 emphasized that this study, with a primary endpoint of OS, demonstrated superiority of pembrolizumab over platinum-based chemotherapy in chemotherapy-naive patients with locally advanced or metastatic NSCLC without sensitizing EGFR or ALK abnormalities and PD-L1 expression of 1% or greater.2 From the authors’ perspectives, this trial may extend the role of pembrolizumab monotherapy as a firstline therapy option for patients with lung cancer expressing any degree of PD-L1 expression, although its use in those with less than 50% PD-L1 expression remains controversial.
Part 1 of the complex CheckMate 227 study was also presented during the Presidential Symposium.3 With a minimum followup of 11.2 months, PFS was significantly longer for nivolumab plus ipilimumab compared with standard platinum-based chemotherapy in patients with high TMB, defined as 10 or more mutations per megabase (HR 0.58, 97.5% CI [0.41, 0.81]; p = 0.0002). These results held up regardless of PD-L1 expression or histology across all subgroups. The side effects of nivolumab/low-dose ipilimumab were manageable.
Finally, Saravia et al.4 presented data on immunotherapy in Hispanic patients. Of note, none of the phase III immunotherapy studies in lung cancer explicitly sought out Hispanic patients. This group of authors presented the largest series to date (216 patients) of immunotherapy outcomes in Hispanic patients, showing that the overall response rate (ORR) seems to be lower compared to their non-Hispanic white counterparts. This study was conducted at Memorial Cancer Institute in collaboration with Sylvester Comprehensive Cancer Center, H. Lee Moffitt Cancer Center and Research Institute (all in Florida, US), and the National Cancer Institute in Peru.
The same group, led by Luis E. Raez, MD, FACP, FCCP, looked for new biomarkers to assess immunotherapy response. In this presentation, investigators focused on use of cfRNA isolated from the plasma of patients with lung cancer.5 The study showed that the changes in cfRNA correlated very well with ORR, as demonstrated by CT scans in patients with lung cancer undergoing immunotherapy. Also, PD-L1 measured in plasma RNA correlated well with tissue PD-L1 testing, making it another promising biomarker to assess immunotherapy response. ✦
About the Author: Dr. Santos Castillero is a thoracic oncologist at the Center for Hematology-Oncology and is a clinical associate professor at Florida Atlantic University. He is also chair of the IASLC Publications Committee.
1. Brahmer J, Rodríguez-Abreu D, Robinson A, et al. KEYNOTE-024 Update: Pembrolizumab vs Platinum-Based Chemotherapy for Advanced NSCLC with PD-L1 Tumor Proportion Score ≥50%. Presented at: IASLC Latin America Conference on Lung Cancer 2018; August 17, 2018; Córdoba, Argentenia.
2. Lopes G, Wu Y, Kudaba I, et al. Phase 3 KEYNOTE-042 Study: Pembrolizumab vs Platinum-Based Chemotherapy as 1l Therapy for Advanced NSCLC with a PD-L1 TPS ≥1%. Presented at: IASLC Latin America Conference on Lung Cancer 2018; August 17, 2018; Córdoba, Argentenia.
3. Mathias C, Reck M, Hellmann M, et al. CheckMate 227: Nivolumab + Ipilimumab vs Chemotherapy as 1L Treatment for Advanced NSCLC With High Tumor Mutational Burden. Presented at: IASLC Latin America Conference on Lung Cancer 2018; August 17, 2018; Córdoba, Argentenia.
4. Saravia D, Raez L, Ruiz R, et al. Clinical Outcomes in Hispanic Patients Treated with Checkpoint Inhibitors. Presented at: IASLC Latin America Conference on Lung Cancer 2018; August 17, 2018; Córdoba, Argentenia.
5. Raez L, Usher J, Danenberg K, et al. New Biomarkers to Follow Therapy Response in Plasma of NSCLC Patients. Presented at: IASLC Latin America Conference on Lung Cancer 2018; August 17, 2018; Córdoba, Argentenia.