The European Lung Cancer Congress brings together key multidisciplinary societies to advance science, disseminate education and improve the practice of lung cancer specialists worldwide. At this year’s event, attendees were able to learn about the current state of lung cancer treatment and update their knowledge on prevention, screening, detection and more.
In patients with non-small cell lung cancer (NSCLC) who have oligometastases to the brain, the optimal treatment sequence of thoracic and metastatic treatment is not well established. One study evaluated the long-term survival of patients with non-small cell lung cancer with oligometastases to the brain who received initial treatment for the primary lung tumor or brain metastases [1]. Patients with cT1-4, N0-3, M1b-c NSCLC with synchronous, limited metastatic disease isolated to the brain who received systemic therapy with radical treatment (surgery, stereotactic radiosurgery of the brain, or radiation to the lung) of both the primary site and metastases in the National Cancer Database from 2010 to 2019 were included. Of 1044 patients, 893 (79.0%) received treatment of brain metastases first and 237 (21.0%) received treatment of the lung first. In the unadjusted Kaplan-Meier analysis, overall survival was similar in patients who treated the brain metastases first compared with patients who treated the lungs first. After multivariable adjusted Cox proportional hazards modeling, no significant difference in overall survival was also observed between the two groups. The results of this study suggest that in patients with non-small cell lung cancer (NSCLC) with synchronous metastatic disease confined to the brain who can tolerate aggressive treatment of the primary and metastatic sites, the order of treatment does not affect overall survival.
The influence of PD-L1 expression
In EGFR-mutated NSCLC, acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) inevitably develops. To date, no conclusive results have been published on the predictive/prognostic role of PDL1 expression in TKI-treated NSCLC with EGFR mutation. A retrospective analysis of patients treated with first (erlotinib/gefitinib), second (afatinib), and third generation (osimertinib) EGFR TKIs was therefore performed [2]. The main objective was to investigate the potential association between PDL1 expression and the efficacy of anti-EGFR treatment in terms of overall survival (OS) and progression-free survival (PFS). Data were collected from 171 patients who received EGFR-TKIs. The most common EGFR alteration was ex19del (52.6%). 26 patients (15.2%) had high PDL1 expression (≥50%). 105 patients (61.4%) were treated with osimertinib, while 22.2%, 12.3%, and 4.1% were treated with gefitinib, afatinib, and erlotinib, respectively. In the overall population, the objective response rate was 61%, mPFS was 19.1 months, and 2-year OS was 61.5%. Patients with PDL1 <50% showed mPFS of 15.4 versus 23.6 months with first/second and third generation TKIs, respectively. In patients with PDL1 ≥50%, mPFS was 8.0 months versus 10.2 months with first/second- and third-generation TKIs, respectively. A significant difference in OS was observed in the high PDL1 subgroup (mOS 24.9 versus 31.3 months with first/second versus third generation TKIs). The study supports the survival benefit of osimertinib compared to first/second generation TKIs, regardless of PDL1 expression.
Invasiveness on the test bench
Correct determination of the degree of invasiveness based on the histologic pattern is of great importance for the development of effective treatment strategies. The analysis of the characteristics of SPN is very important. The aim of the study was to investigate the value of CT parameters in predicting the degree of risk [3]. Patients with clinical stage 0 to IB NSCLC who had undergone radical surgical resection and were pathologically diagnosed with invasive adenocarcinoma were included. Preoperative high-resolution CT scans with three-dimensional reconstruction were performed in all patients in this study. A total of 355 SPNs were evaluated. CT findings revealed 71 pure GGO lesions (20.0%), 206 partially solid GGO lesions (58.0%), and 78 solid lesions (22.0%). In univariate logistic regression analysis, maximum CT score, minimum CT score, mean CT score, CT findings, and clinical stage were significantly related to high-risk SPN. CT value mean and CT findings were independent significant factors in multivariate analysis. The mean CT score and CT findings correlated independently with high-risk SPN in multivariate analysis and should be helpful in deciding the treatment regimen, especially the extent of surgical resection.
Resection possible after immunotherapy
The development of immunotherapy has significantly increased survival in advanced NSCLC. A study now aimed to analyze outcome predictors, surrogate outcomes, and PROMs after neoadjuvant immunotherapy for unresectable NSCLC [4]. Included were originally unresectable NSCLC patients who received immunotherapy (ICI) ± platinum-based chemotherapy and/or radiotherapy and underwent surgical resection after response. 19 underwent salvage surgery after ICI. 14 had a partial response (73.6%), and five had stable disease. Diagnosis was made by EBUS in eight cases (42.1%), FNAB in seven cases (36.8%), and metastatic biopsy in four cases (21.0%). 11 (57.9%) were treated with platinum-based neoadjuvant chemotherapy before or with ICI, 1 (5.2%) with pemetrexed before ICI, 5 (26.3%) with radiotherapy for metastatic control. 7 (36.8%) received adjuvant therapy (5 [26,3%] pembrolizumab, 1 [5,2%] pemetrexed, 1 [5,2%] pemetrexed + pembrolizumab). The median OS was 19 months. After two months, 94.7% were alive (6 months: 89.5%; 31 months: 79.5%). PROMs were evaluated retrospectively at 30 days/1 year, with significant reductions in cough, treatment adverse events, and surgery-related problems. Radical surgical resection following immunotherapy/immunochemotherapy was shown to be feasible and safe for selected initially unresectable NSCLC. Symptoms and surgical outcomes were lower and quality of life was higher because this was a select group of highly motivated patients.
Tumor doubling time illuminated in more detail
Tumor growth patterns have important implications for setting screening intervals, treatment decisions, and predicting prognosis. The aim of one study was to characterize the tumor doubling time (VDT) or growth pattern of primary lung cancer and to identify factors associated with rapid and indolent growth patterns [5]. For this purpose, studies were identified that reported volumetrically measured tumor VDT or growth patterns of pathologically confirmed primary lung cancer without intervention. Data were abstracted to calculate pooled VDT and find correlations of growth patterns. Meta-analysis was performed for the pooled mean VDT for lung cancer overall and for different histologic subtypes. Twenty-six studies involving 2275 patients with primary lung cancer (mean age ranged from 54.6 to 72.0 years) were identified. The overall pooled mean VDT was 213 days. In subgroup analyses, the pooled median VDT of adenocarcinoma, adenocarcinoma (subsolid), squamous cell carcinoma, small cell lung cancer, and other lung cancer was 241, 731, 136, 71, and 183 days, respectively. Rapid growth accounted for 64.8% of total lung cancer and 23.7% of adenocarcinoma. The most consistent correlates of rapid tumor growth included nodal solidity, histologic subtype of nonadenocarcinoma, and invasiveness of adenocarcinoma. The median VDT for lung cancer overall is about 400 days (range 139 to 357 days), with about two-thirds being rapid. The most consistent correlations were demonstrated for solidity and histology subtypes.
TKIs in daily practice
EGFR mutations occur in approximately 10-50% of NSCLC patients. EGFR TKIs have become established as the optimal first-line treatment in the advanced stage. A study has now taken a closer look at real-life treatment patterns in clinical practice in nine countries [6]. A retrospective medical record review was conducted in Argentina, Belgium, Brazil, India, the Netherlands, Russia, Singapore, Switzerland, and Turkey from June to September 2021. A total of 947 case report forms were collected for patients with advanced/metastatic NSCLC (stage IIIB/C/IV).
The median turnaround time for EGFR testing was found to be longer than the 10 working days recommended in the guidelines. This suggests that EGFR testing procedures need to be improved to ensure timely initiation of targeted therapy. In patients treated with an EGFR TKI as 1L therapy, TTFST was favorable in this real-world study. However, 31% of EGFRm patients did not receive a 1L EGFR TKI. The results suggest an unmet need to optimize treatment strategies for patients with advanced NSCLC with EGFRm.
Optimizing the treatment of edema with MET-TKIs
Peripheral edema (PE), a side effect of MET-TKIs, can affect treatment adherence. Under real conditions, it was investigated how an optimized treatment could look like [7]. An online survey assessed onset, time to resolution, symp-toms, prevention, and management of PE during treatment with four available MET-TKIs for MET exon 14-skipping NSCLC.
A total of 26 physicians participated. 77% of physicians reported that more than 50% of patients had PE with MET-TKI. Low mobility, age, and duration of treatment were cited as common risk factors. Heart disease was the most common comorbidities. The occurrence of PE, which can last more than six months, and time to improvement were found to be similar among the MET-specific TKIs, with crizotinib (a multi-kinase TKI) resulting in less frequent, less severe, and less durable PE. Swollen extremities were cited as the most bothersome symptom by 96% of physicians, followed by pain (46%) and weight gain (31%), with time to improvement of up to three months for mild to moderate PE and up to six months for severe PE. Pain (81% vs 23%) and skin lesions (50% vs 23%) were more common in severe and mild PE, respectively. 62% of physicians performed multiple preventive measures simultaneously (bed/foot positioning [88%], compression stockings [69%], massage [63%], reduction of salt intake [50%], exercise/diuretics [25%]); only 13% performed them at baseline. The most common therapies were diuretics (89%), nonpharmacologic measures (85%), MET-TKI interruption (73%), and dose reduction (65%). 4/5 of Chinese physicians also reported having consulted vascular specialists.
From the survey, the most important unmet needs for PE management are the development of effective therapy, the incorporation of preventive measures at the start of treatment with MET-TKI (not only when PE occurs), and clarification of the mechanism of action associated with MET-TKI.
Congress: European Lung Cancer Congress (ELCC) 2023
Literature:
- Kumar A, Kuhn S, Potter A, et al.: Treatment Sequence for Non-small-cell Lung Cancer with Brain Oligometastases does not Impact Overall Survival. Advanced NSCLC. 17P.
- Belluomini L, Ferrara M, Sposito M, et al.: Impact of PDL1 expression on Outcomes of patients with EGFR mutant NSCLC treated with EGFR TKIs: first results of the POET study. Advanced NSCLC. 23P.
- Jiang L, Jiang S, Luo Q: Quantitative CT parameters in predicting the degree of risk of solitary pulmonary nodules. Early stage NSCLC. 88P.
- Bertolaccini L, Mohamed S, Galetta D, et al.: Predictors, surrogate and patient-reported outcomes in neoadjuvant immunotherapy for lung cancer: A single center retrospective study. Early stage NSCLC. 92P.
- Jiang B, Han D, Heuvelmans M, et al.: Volumetric tumor volume doubling time in lung cancer: a systematic review and meta-analysis. Imaging and staging. 110P
- Samol J, Demedts I, Erman M et al. Real-World Use of Tyrosine Kinase Inhibitors (TKI) in Epidermal Growth Factor Receptor mutated (EGFRm) Advanced Non-Small Cell Lung Cancer (NSCLC) in Nine Countries. Advanced NSCLC. 26P.
- Ferrara R, Vansteenkiste JF, Yang X et al. Real-world experience of MET TKI-induced peripheral edema Advanced NSCLC. 33P.
InFo ONKOLOGIE & HÄMATOLOGIE 2023, 11(3): 30–31
