Update in Immunotherapy for Advanced Non-Small Cell Lung Cancer: Optimizing Treatment Sequencing and Identifying the Best Choices.

The introduction of immunotherapy has brought about a paradigm shift in the management of advanced non-small cell lung cancer (NSCLC). It has not only significantly improved the prognosis of patients but has also become a cornerstone of treatment, particularly in those without oncogenic driver mutations. Immune checkpoint inhibitors (ICIs) play a crucial role in the treatment of lung cancer and can be classified into two main groups: Anti-cytotoxic T lymphocyte antigen-4 (Anti-CTLA-4) and anti-T-cell receptor programmed cell death-1 or its ligand (Anti-PD-1 and Anti-PD-L1). Certainly, the landscape of approved first line immunotherapeutic approaches has expanded to encompass monotherapy, immunotherapy-exclusive protocols, and combinations with chemotherapy. The complexity of decision-making in this realm arises due to the absence of direct prospective comparisons. However, a thorough analysis of the long-term efficacy and safety data derived from pivotal clinical trials can offer valuable insights into optimizing treatment for different patient subsets. Moreover, ongoing research is investigating emerging biomarkers and innovative therapeutic strategies that could potentially refine the current treatment approach even further. In this comprehensive review, our aim is to highlight the latest advances in immunotherapy for advanced NSCLC, including the mechanisms of action, efficacy, safety profiles, and clinical significance of ICI.

Breast cancer subtype and clinical characteristics in women from Peru.

Introduction: Breast cancer is a heterogeneous disease, and the distribution of the different subtypes varies by race/ethnic category in the United States and by country. Established breast cancer-associated factors impact subtype-specific risk; however, these included limited or no representation of Latin American diversity. To address this gap in knowledge, we report a description of demographic, reproductive, and lifestyle breast cancer-associated factors by age at diagnosis and disease subtype for The Peruvian Genetics and Genomics of Breast Cancer (PEGEN-BC) study. Methods: The PEGEN-BC study is a hospital-based breast cancer cohort that includes 1943 patients diagnosed at the Instituto Nacional de Enfermedades Neoplásicas in Lima, Peru. Demographic and reproductive information, as well as lifestyle exposures, were collected with a questionnaire. Clinical data, including tumor Hormone Receptor (HR) status and Human Epidermal Growth Factor Receptor 2 (HER2) status, were abstracted from electronic medical records. Differences in proportions and mean values were tested using Chi-squared and one-way ANOVA tests, respectively. Multinomial logistic regression models were used for multivariate association analyses. Results: The distribution of subtypes was 52% HR+HER2-, 19% HR+HER2+, 16% HR-HER2-, and 13% HR-HER2+. Indigenous American (IA) genetic ancestry was higher, and height was lower among individuals with the HR-HER2+ subtype (80% IA vs. 76% overall, p=0.007; 152 cm vs. 153 cm overall, p=0.032, respectively). In multivariate models, IA ancestry was associated with HR-HER2+ subtype (OR=1.38,95%CI=1.06-1.79, p=0.017) and parous women showed increased risk for HR-HER2+ (OR=2.7,95%CI=1.5-4.8, p<0.001) and HR-HER2- tumors (OR=2.4,95%CI=1.5-4.0, p<0.001) compared to nulliparous women. Multiple patient and tumor characteristics differed by age at diagnosis (<50 vs. >=50), including ancestry, region of residence, family history, height, BMI, breastfeeding, parity, and stage at diagnosis (p<0.02 for all variables). Discussion: The characteristics of the PEGEN-BC study participants do not suggest heterogeneity by tumor subtype except for IA genetic ancestry proportion, which has been previously reported. Differences by age at diagnosis were apparent and concordant with what is known about pre- and post-menopausal-specific disease risk factors. Additional studies in Peru should be developed to further understand the main contributors to the specific age of onset and molecular disease subtypes in this population and develop population-appropriate predictive models for prevention.

Real-world outcomes of anti-EGFR therapy in advanced non-small cell lung cancer EGFR mutated in Peru.

BACKGROUND: Despite the advances in the management of advanced non-small cell lung cancer (NSCLC), the access to genetic profiling and target therapies remains a challenge in Latin America, even in countries with a higher rate of targetable mutations. The aim of this study is to evaluate the clinical outcomes of anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) treatment in a Peruvian real-world setting. METHODS: This is a retrospective study of recurrent or advanced NSCLC EGFR mutated patients diagnosed and treated with anti-EGFR TKI at Instituto Nacional de Enfermedades Neoplásicas (INEN) between January 1, 2015 to December 31, 2020. The outcomes were objective response rate (ORR), progression free survival (PFS), and overall survival (OS). RESULTS: We identify 613 stage IV or recurrent NSCLC patients who were tested for EGFR mutations and found a pathogenic mutation in 39.5% of patients. Only 51.2% of them received anti-EGFR TKI as institutional treatment. ORR was 58%, after median follow-up of 32 months, the estimated median PFS was 13.9 months (11.1-16.7 months), and the estimated median OS was 21.7 months (18.5-24.9 months). No differences were found in PFS according to line of treatment or brain metastases at diagnosis (p = 0.46 and p = 0.07, respectively), respect to OS there were no differences line of treatment (p = 0.12), significant difference were found in presence of brain metastases (p = 0.006). CONCLUSION: Our study demonstrates that erlotinib for advanced NSCLC harboring EGFR-activating mutations is effective even in patients usually excluded from clinical trial, like those previously exposed to one or more lines of chemotherapy or with brain metastases.

The impact of telemedicine on cancer care: real-world experience from a Peruvian institute during the COVID-19 pandemic.

Background: The COVID-19 pandemic caused discontinuities in cancer care (CC) in most countries. Here, the authors describe the real-world impacts of implementing a contingency plan employing telemedicine for CC. Methods: A retrospective study of patients who received CC through telemedicine at the Instituto Nacional de Enfermedades Neoplasicas, Peru, from March 2020 to February 2021 was conducted. Impacts were measured by comparing the amount of CC administered during the pandemic versus the prior year. Results: A total of 16,456 telemedicine visits were carried out. An annual comparative analysis showed a gap of 23% and telemedicine accounted for 27.6% of the total CC administered during the pandemic. A high (4.50/5) level of patient satisfaction with telemedicine was reported. Conclusion: Telemedicine is an important tool to facilitate the continuity of CC.

Genomic landscape of lung cancer in the young.

Background: Lung cancer in the young is a rare entity of great interest due to the high frequency of targetable mutations. In this study, we explored the genomic landscape of non-small cell lung cancer (NSCLC) in young patients and compared it with genetic alterations in older patients. Methods: Comparative study of the genomic profile of NSCLC young (≤40 years old) vs older patients (>40 years old) from Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru. Archival paraffin-embedded tumor samples were profiled with FoundationOne CDx assay to identify short variants alterations (insertions and deletions), copy number variations (CNV), tumor mutational burden and microsatellite instability in 324 driver genes and rearrangements in 28 commonly rearranged genes. A targetable alteration was defined as any alteration in a driver oncogene for which an FDA approved therapy existed at the time of study enrollment. Results: Overall, 62 tumors were profiled, 32 from young and 30 from older patients. All clinicopathological features (smoking status, clinical stage, and histology) were similar between groups, except for gender (65.6% of females in the younger group vs 40% in the older group, P=0.043). At least one actionable mutation was present in 84.4% and 83.3% in younger and older patients, respectively. Alteration rates in the main genes were: BRAF, 3.1%(n=1) vs 0%; EGFR, 46.9% (n=15) vs 43.3% (n=13); ERBB2, 12.5% (n=4) vs 16.7% (n=5); KRAS, 15.6% (n=5) vs 16.7% (n=5); ALK, 6.3% (n=2) vs 3.3% (n=1); RET, 0.0% vs 3.3% (n=1); ROS1, 3.1% (n=1) vs 3.3% (n=1); NTRK1, 0.0% vs 3.3% (n=1) and MET, 3.1% (n=1) vs 13.3% (n=4). Mean TMB was 4.04 Mut/Mb (SD ± 3.98) for young vs 8.06 Mut/Mb (SD ± 9.84) for older patients (P=0.016). There were not significant differences in CNV, frequency of gene rearrangements, or microsatellites instability. Conclusion: NSCLC in the young in our cohort was characterized by a high frequency of actionable genetic aberrations and a low TMB, which was also true for our older patients. The enrichment of actionable mutations in young patients described in other reports might be attributed to differences in the etiology and clinicopathological characteristics between younger and older patients and therefore not be applicable to all populations.

Association between PIK3CA Mutations in Blood and Tumor-Infiltrating Lymphocytes in Peruvian Breast Cancer Patients.

OBJECTIVE: To evaluate the relationship between circulating tumor DNA (ctDNA) presence and tumor features including tumor-infiltrating lymphocyte (TIL) levels in Peruvian breast cancer patients. MATERIALS AND METHODS: This was a prospective study conducted at the Instituto Nacional de Enfemedades Neoplasicas, Peru. We evaluated level of TIL and PIK3CA mutations in ctDNA. Clinical characteristics, including outcome data, were collected from the patient file. Survival was calculated from the date of blood sample drawn to the event time. Data collected were analyzed using SPSS software version 25. RESULTS: We analyzed plasma samples from 183 breast cancer patients. most cases were of Luminal-B (44.8%) phenotype and stage II (41.5%), and median stromal TIL was 30%. PIK3CA mutation in ctDNA was detected in 35% cases (most with E545K) and was associated with lower TIL level (p=0.04). PIK3CA in ctDNA tended to be associated with advanced stages (p=0.09) in the whole series and with higher recurrence rates (p=0.053) in the non-metastatic setting. Patients with presence of PIK3CA in ctDNA tended to have shorter survival (p=0.083). CONCLUSION: Presence of PIK3CA mutation in ctDNA was frequently found in our Peruvian breast cancer series, was associated with lower TIL levels and tended to predict poor outcomes.

Lung Cancer in the Young.

INTRODUCTION: Median age at diagnosis of lung cancer is 70 years. Its presentation in patients 40 or younger is uncommon and it has been proposed that maybe it is a different disease due to its clinical characteristics and genetic makeup. There are a limited number of studies in this population and they report different clinic-pathological characteristics in comparison with older patients. METHODS: We described the incidence of lung cancer patients diagnosed at age 40 or younger at the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima-Peru; from 2009 to 2017 and evaluated the characteristic of NSCLC. Epidemiologic and clinic-pathological data was collected from clinical files. Analysis was carried out using SPSSvs19 software. RESULTS: We identified 3823 patients with lung cancer seen at INEN during the study period. Among these, 166 (4.3%) patients were 40 years or younger, and 137/166 (82.5%) were NSCLC. Median age at diagnosis was 36 years (range 14-40 years) and 59.1% of patients were female. A smoking history was present in 14.4% of patients. Frequent symptoms at diagnosis were cough (62.0%), chest pain (51.8%) and dyspnea (40.9%). Adenocarcinoma was the most common histological type (63.3%). Most patients had advanced disease at diagnosis (84.7%). The median overall survival was 8.2 months. CONCLUSIONS: The proportion of young patients with lung cancer in our population is higher than that reported in the most recent literature. Lung cancer in the young is mostly sporadic, more frequent in women, usually adenocarcinoma type and it presents with advanced disease, resulting in a very poor survival.