Genomic and immunologic tumor biomarker testing has dramatically changed the prognosis of patients, particularly those treated for advanced/metastatic non-squamous non-small-cell lung cancer (aNSCLC) ...when access to targeted agents is available. It remains unclear whether older patients have access to therapy-predictive biomarker testing techniques in the same proportion as younger patients. This study aims to compare the proportion of biomarker testing performed in non-squamous aNSCLC at diagnosis between patients aged ≥70 years old and their younger counterparts.
We conducted a retrospective analysis using the Epidemio-Strategy and Medical Economics (ESME) Advanced or Metastatic Lung Cancer Data Platform, a French multicenter real-life database. All patients with non-squamous aNSCLC diagnosed between 2015 and 2018 were selected. Biomarker testing corresponded to at least one molecular alteration and/or PD-L1 testing performed within 1 month before or 3 months after the aNSCLC diagnosis.
In total, 2848 patients aged ≥70 years and 6900 patients aged <70 years were included. Most patients were male. The proportion of current smokers at diagnosis was higher in the <70 years group (42% vs. 17%,
< 0.0001). There was no significant difference in the proportion of biomarker testing performed between the two groups (63% vs. 65%,
= 0.15).
mutations were significantly more common in the older group (22% vs. 12%,
< 0.0001) and
mutations significantly more frequent in the younger group (39% vs. 31%
< 0.0001). The distribution of other driver mutations (
V600E,
and
) was similar across age. In the multivariable analysis, factors independently associated with biomarker testing were gender, smoking status, history of COPD, stage at primary diagnosis, and histological type.
Age is not a barrier to biomarker testing in patients with aNSCLC.
We sought to determine the long-term (median follow-up, 7.5 years) predictive power of human MutS homologue 2 (MSH2) immunohistochemical expression in patients who enrolled in the International ...Adjuvant Lung Trial.
We tested the interaction between MSH2 and the allocated treatment (chemotherapy versus observation) in a Cox model adjusted on clinicopathologic variables. The significance level was set at 0.01.
MSH2 levels were low in 257 (38%) and high in 416 (62%) tumors. The benefit from chemotherapy was likely different according to MSH2 (interaction test, P = 0.06): there was a trend for chemotherapy to prolong overall survival when MSH2 was low hazard ratio (HR), 0.76; 95% confidence interval (95% CI), 0.59-0.97; P = 0.03, but not when MSH2 was high (HR, 1.12; 95% CI, 0.81-1.55; P = 0.48). In the control arm, the HR was 0.66 (95% CI, 0.49-0.90; P = 0.01) when MSH2 was high. When combining MSH2 with excision repair cross-complementing group 1 (ERCC1) into four subgroups, the benefit of chemotherapy decreased with the number of markers expressed at high levels (P = 0.01). A similar decrease was noted when combining MSH2 and P27 (P = 0.01). Chemotherapy prolonged overall survival in the combined low MSH2/low ERCC1 subgroup (HR, 0.65; 95% CI, 0.47-0.91; P = 0.01) and in the combined low MSH2/low P27 subgroup (HR, 0.65; 95% CI, 0.46-0.93; P = 0.01).
MSH2 expression is a borderline significant predictor of a long-term benefit from adjuvant cisplatin-based chemotherapy in patients with completely resected lung cancer. MSH2 combined with ERCC1 or P27 may identify patients most likely to benefit durably from chemotherapy.
Background
An international consensus proposed in 2011 a definition and classification system for cachexia (CAX), mainly based on weight loss, sarcopenia skeletal muscle mass (SMM) loss, ...inflammation, and anorexia. The aim of this study was to stage CAX in non‐small‐cell lung cancer (NSCLC) patients by using a classification based on the Fearon criteria and supported by quantifiable parameters.
Methods
This was a cross‐sectional and non‐interventional multicentre study. SMM was assessed by analysing L3 computed tomography‐scan images. Patients completed the anorexia/CAX subscale of the Functional Assessment of Anorexia/Cachexia Therapy, EORTC QLQ‐C30 quality of life (QoL) and International Physical Activity Questionnaire (IPAQ).
Results
Patients were recruited in 56 sites. The analysis population comprised 531 patients, and SMM was assessed in 312 patients. Male patients were 66.5%, with a mean (SD) age of 65.2 (10.0) years, 79.9% were PS 0–1, and the tumour stage was mainly IIIB‐IV (87.3%). Overall, 38.7% of patients had CAX, 33.8% pre‐CAX, and 0.9% refractory CAX. Molecular tumour profiles were significantly associated with the presence of CAX: 23.9% in EGFR, ALK, ROS1, BRAF, or HER2+ patients, 41.4% in K‐RAS+, and 43.2% in patients with no molecular abnormality (P = 0.003). The more advanced the CAX stage, the poorer the scores of functional items of the QoL (P < 0.001) and International Physical Activity Questionnaire (P < 0.001). Sarcopenia was present in 66.7% of CAX and 68.5% of pre‐CAX patients. Overall, 43.8% of pre‐CAX patients had only sarcopenia with limited weight loss (≤2%) and no anorexia.
Conclusions
This is the first study to show the distribution of CAX in a population of NSCLC patients and an association between molecular abnormality in NSCLC and CAX. The original Fearon classification for CAX stages was supported by the associated functional QoL scores and physical activity levels, resulting in a clinically relevant system for detection of early stages of CAX.
Brigatinib is a next-generation ALK inhibitor (ALKi) that shows efficacy in ALK inhibitor naïve and post-crizotinib ALK+ advanced NSCLCs (aNSCLCs). The efficacy of brigatinib was retrospectively ...assessed in patients with aNSCLCs included in the brigatinib French Early-Access Program (1 August 2016−21 January 2019). The primary endpoint was investigator-assessed progression-free survival (invPFS) and the primary analysis was updated in 2021 with a longer follow-up, focused on post-brigatinib lorlatinib efficacy. Sixty-six centers included 183 patients: median age 60 ± 12.7 years; 78.3% never/former smokers; median of 3 ± 1 previous lines and 2 ± 0.5 ALKis; 37.1% ECOG PS 2 and 55.6% >3 metastatic sites. The median follow-up from brigatinib initiation was 40.4 months (95% CI 38.4−42.4). InvPFS was 7.4 months (95% CI 5.9−9.6), median duration of treatment (mDOT) was 7.3 months (95% CI 5.8−9.4) and median overall survival (mOS) was 20.3 months (95% CI 15.6−27.6). The median DOT and OS from brigatinib initiation tend to decrease with the number of ALK inhibitors used in previous lines of therapy. Based on the data collected, 92 (50.3%) patients received ≥1 agent(s) post-brigatinib and 68 (73.9%) of them received lorlatinib, with 51 (75%) immediately receiving it post-brigatinib, 12 (17.6%) receiving it after one and 5 (7.4%) after ≥2 subsequent treatments. The median follow-up was 29.9 (95% CI 25.7−33.1) months. Lorlatinib mDOT was 5.3 (95% CI 3.6−7.6) months with a median OS from lorlatinib initiation of 14.1 (95% CI 10.3−19.2) months. The results of the brigALK2 study confirm the efficacy of brigatinib in a population of heavily pretreated ALK+ aNSCLC patients and provide new data on the activity of lorlatinib after brigatinib.
•SBRT fore rare oligoprogressive (70%)/oligorecurrent SCLC.•The median LC/DR/OS were NR, 4.5 and 17.2 months, respectively.•Initial LS associated with decreased post-SBRT OS and DR.
The role of local ...ablative treatments, including stereotactic body radiotherapy (SBRT), is an area of active research in oligometastatic patients. Small cell lung cancer (SCLC) has a poor prognosis, with common diffuse metastatic evolution. We evaluated the outcomes after SBRT in uncommon oligoprogressive/oligorecurrent SCLC presentation.
Data of SCLC patients who received SBRT for oligoprogressive/oligorecurrent metastatic disease at four centers were retrospectively analyzed. Patients with synchronous oligometastatic disease, SBRT for primary lung tumor and brain radiosurgery were not included. Relapse and survival rates were defined as the time between the date of SBRT and the first event.
Twenty patients (60% with initially limited-disease LD) presenting 24 lesions were identified. Oligoprogression and oligorecurrence were observed in 6/20 (30%) and 14/20 (70%) patients, respectively. SBRT was delivered to one (n = 16) to two (n = 4) lesions (median size, 26 mm), mainly to lung n = 17/24 metastases. At a median follow-up of 2.9 years, no local relapse was observed and 15/20 patients experienced a distant relapse (DR). The median DR and OS were 4.5 months (95 %CI: 2.9–13.7 months) and 17.2 months (95 %CI: 7.5–65.2 months), respectively. The 3-year distant control and OS rates were 25% (95 %CI: 6–44%) and 37% (95 %CI: 15–59%), respectively. Initial LD (vs extensive-disease) was the only prognosis factor associated with a lower risk of post-SBRT DR (HR: 0.3; 95% CI: 0–0.88; p = 0.03). There was no severe observed SBRT-related toxicities.
Prognosis was poor, with DR occurring in most patients. However, local control was excellent and long term response after SBRT may rarely occur in patients with oligoprogressive/oligorecurrent SCLC. Local ablative treatments should be discussed in a multidisciplinary setting on well-selected cases.
Background Our aim was to explore the prognostic value of anthropometric parameters in a large population of patients treated with immunotherapy. Methods We retrospectively included 623 patients with ...advanced non-small cell lung cancer (NSCLC) (n=318) or melanoma (n=305) treated by an immune-checkpoint-inhibitor having a pretreatment (thorax-)abdomen-pelvis CT scan. An external validation cohort of 55 patients with NSCLC was used. Anthropometric parameters were measured three-dimensionally (3D) by a deep learning software (Anthropometer3DNet) allowing an automatic multislice measurement of lean body mass, fat body mass (FBM), muscle body mass (MBM), visceral fat mass (VFM) and sub-cutaneous fat mass (SFM). Body mass index (BMI) and weight loss (WL) were also retrieved. Receiver operator characteristic (ROC) curve analysis was performed and overall survival was calculated using Kaplan-Meier (KM) curve and Cox regression analysis. Results In the overall cohort, 1-year mortality rate was 0.496 (95% CI: 0.457 to 0.537) for 309 events and 5-year mortality rate was 0.196 (95% CI: 0.165 to 0.233) for 477 events. In the univariate Kaplan-Meier analysis, prognosis was worse (p<0.001) for patients with low SFM (<3.95 kg/m 2 ), low FBM (<3.26 kg/m 2 ), low VFM (<0.91 kg/m 2 ), low MBM (<5.85 kg/m 2 ) and low BMI (<24.97 kg/m 2 ). The same parameters were significant in the Cox univariate analysis (p<0.001) and, in the multivariate stepwise Cox analysis, the significant parameters were MBM (p<0.0001), SFM (0.013) and WL (0.0003). In subanalyses according to the type of cancer, all body composition parameters were statistically significant for NSCLC in ROC, KM and Cox univariate analysis while, for melanoma, none of them, except MBM, was statistically significant. In multivariate Cox analysis, the significant parameters for NSCLC were MBM (HR=0.81, p=0.0002), SFM (HR=0.94, p=0.02) and WL (HR=1.06, p=0.004). For NSCLC, a KM analysis combining SFM and MBM was able to separate the population in three categories with the worse prognostic for the patients with both low SFM (<5.22 kg/m 2 ) and MBM (<6.86 kg/m 2 ) (p<0001). On the external validation cohort, combination of low SFM and low MBM was pejorative with 63% of mortality at 1 year versus 25% (p=0.0029). Conclusions 3D measured low SFM and MBM are significant prognosis factors of NSCLC treated by immune checkpoint inhibitors and can be combined to improve the prognostic value.
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