JTO Clinical and Research Reports最新文献

Background

Improving the method for selecting participants for lung cancer (LC) screening is an urgent need. Here, we compared the performance of the Helseundersøkelsen i Nord-Trøndelag (HUNT) Lung Cancer Model (HUNT LCM) versus the Dutch-Belgian lung cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON)) and 2021 United States Preventive Services Task Force (USPSTF) criteria regarding LC risk prediction and efficiency.

Methods

We used linked data from 10 Norwegian prospective population-based cohorts, Cohort of Norway. The study included 44,831 ever-smokers, of which 686 (1.5%) patients developed LC; the median follow-up time was 11.6 years (0.01–20.8 years).

Results

Within 6 years, 222 (0.5%) individuals developed LC. The NELSON and 2021 USPSTF criteria predicted 37.4% and 59.5% of the LC cases, respectively. By considering the same number of individuals as the NELSON and 2021 USPSTF criteria selected, the HUNT LCM increased the LC prediction rate by 41.0% and 12.1%, respectively. The HUNT LCM significantly increased sensitivity (p < 0.001 and p = 0.028), and reduced the number needed to predict one LC case (29 versus 40, p < 0.001 and 36 versus 40, p = 0.02), respectively. Applying the HUNT LCM 6-year 0.98% risk score as a cutoff (14.0% of ever-smokers) predicted 70.7% of all LC, increasing LC prediction rate with 89.2% and 18.9% versus the NELSON and 2021 USPSTF, respectively (both p < 0.001).

Conclusions

The HUNT LCM was significantly more efficient than the NELSON and 2021 USPSTF criteria, improving the prediction of LC diagnosis, and may be used as a validated clinical tool for screening selection.

Both sotorasib and adagrasib are approved for use in metastatic KRAS^G12C-mutated NSCLC after cancer progression on chemotherapy and immunotherapy. Hepatoxicity is a commonly encountered adverse effect of both agents, and little data exists about the safety of sequential use of these agents when hepatotoxicity is encountered. In this case report, we describe a patient who developed recurrent hepatotoxicity with sotorasib and was able to switch to adagrasib without hepatotoxicity and subsequently experienced a prolonged cancer response. We also describe a previously unreported adagrasib adverse effect of photoinduced skin hyperpigmentation.

Introduction

In the placebo-controlled, phase 3 PACIFIC trial, durvalumab significantly prolonged progression-free survival (PFS) (p < 0.0001) and overall survival (OS) (p = 0.00251) in patients with unresectable stage III NSCLC and no progression after platinum-based concurrent chemoradiotherapy (cCRT). Pneumonitis or radiation pneumonitis (PRP) was common in both arms. We report exploratory analyses evaluating the association of symptomatic (grade ≥2) PRP (G2+PRP) with baseline factors and clinical outcomes.

Methods

Patients with WHO performance status of 0 or 1 were randomized (2:1) to 12 months of durvalumab or placebo, 1 to 42 days after cCRT. Associations between baseline factors and on-study G2+PRP in durvalumab-treated patients were investigated using univariate and multivariate logistic regression. PFS and OS were analyzed using Cox proportional hazards models adjusted for time-dependent G2+PRP plus covariates for randomization stratification factors without and with additional baseline factors.

Results

On-study G2+PRP occurred in 94 of 475 (19.8%) and 33 of 234 patients (14.1%) on durvalumab and placebo, respectively (median follow-up, 25.2 mo); grade greater than or equal to 3 PRP was uncommon (4.6% and 4.7%, respectively). Time to onset and resolution of G2+PRP was similar with durvalumab and placebo. Univariate and multivariate analyses identified patients treated in Asia, those with stage IIIA disease, those with performance status of 1, and those who had not received induction chemotherapy as having a higher risk of G2+PRP. PFS and OS benefit favoring durvalumab versus placebo was maintained regardless of time-dependent G2+PRP.

Conclusions

Factors associated with higher risk of G2+PRP with durvalumab after cCRT were identified. Clinical benefit was maintained regardless of on-study G2+PRP, suggesting the risk of this event should not deter the use of durvalumab in eligible patients with unresectable stage III NSCLC.

Introduction

Multiple clinical trials have revealed the benefit of immunotherapy (IO) for NSCLC, including unresectable stage III disease. Our aim was to investigate the impact of IO use on treatment and outcomes of potentially resectable stage IIIA NSCLC in a broader nationwide patient cohort.

Methods

We queried the National Cancer Database (2004–2019) for patients with stage IIIA (T1-2N2) NSCLC. Treatment and survival were evaluated with descriptive statistics, logistic regression, Kaplan-Meier analysis, and Cox proportional hazards modeling.

Results

Overall, 5.5% (3777 of 68,335) of patients received IO. IO use was uncommon until 2017, but by 2019, it was given to 40.1% (1544 of 2308) of stage IIIA patients. The increased use of IO after 2017 was associated with increased definitive chemoradiation treatment (54.2% [6800 of 12,535] from years 2017 to 2019 versus 46.9% [26,251 of 55,914] from 2004 to 2016, p < 0.001) and less use of surgery (18.1% [2266 of 12,535] from years 2017 to 2019 versus 22.0% [12,300 of 55,914] from 2004 to 2016, p < 0.001). IO treatment was associated with significantly better 5-year survival in the entire cohort (36.9% versus 23.4%, p < 0.001) and the subsets of patients treated with chemoradiation (37.2% versus 22.7%, p < 0.001) and surgery (48.6% versus 44.3%, p < 0.001). Pneumonectomy use decreased with increased IO treatment (5.1% of surgical patients [116 of 2266] from years 2017 to 2019 versus 9.2% [1127 of 12,300] from 2004 to 2016, p < 0.001).

Conclusions

Increased use of IO was associated with a change in treatment patterns and improved survival for patients with stage IIIA(N2) NSCLC.

Neoadjuvant intratumoral cisplatin has the potential to generate substantial cytotoxicity and immune priming within the tumor environment, while minimizing systemic, off-target, adverse events. We initiated a phase 1A, 3+3 dose-ranging study of neoadjuvant, intratumoral cisplatin, delivered through endobronchial ultrasound bronchoscopy, in the same procedure as the initial diagnosis. There were no dose-limiting toxicity identified at the 20mg level

Introduction

Biomarker testing in oncology is fundamental for targeted therapy use and clinical trial participation. Factors contributing to previously identified racial disparities in biomarker testing remain unclear. This study investigated biomarker testing, clinical trial participation, and targeted therapy by race among patients with metastatic lung cancer with Medicaid coverage in the United States.

Methods

The Merative MarketScan Medicaid claims database was used for this study to identify patients diagnosed with having metastatic lung cancer between 2017 and 2019 with at least 121 days of follow-up. Racial differences in biomarker testing, clinical trial enrollment, and targeted therapy use were analyzed using chi-square/t tests followed by logistic regression for confounding covariates.

Results

A total of 3845 patients were eligible. A total of 970 (25.2%) patients included in this study were Black. Biomarker testing was observed among 57.0%, targeted therapy among 4.6%, and 2.6% of the study cohort had evidence of clinical trial participation. No significant disparities between Black and White races were identified. Younger age and metastatic disease at initial diagnosis were the strongest independent factors associated with increased biomarker testing. Biomarker testing was positively associated with targeted therapy use (OR = 1.69, p = 0.005).

Conclusions

Patients with metastatic lung cancer with Medicaid coverage were found to have exceedingly low biomarker testing rates; only 57% had evidence of any biomarker testing. Although no consistent differences between Black and White races were identified, this study calls attention to care experienced by socioeconomically disadvantaged patients with metastatic lung cancer in the United States.

Introduction

Multiple programmed death-ligand 1 (PD-L1) immunohistochemistry assays performed using different antibodies including DAKO 22C3, DAKO 28-8, and Ventana SP142 PD-L1—predictive markers for response to various immune checkpoint inhibitors in NSCLC—have been approved in several countries. The differences in multiple PD-L1 immunohistochemistry assay results in predicting the therapeutic response to combined chemoimmunotherapy in patients with NSCLC remain unclear.

Methods

In this multicenter prospective observational study, we monitored 70 patients with advanced NSCLC treated with combined chemoimmunotherapy at 10 institutions in Japan. The expression of PD-L1 in pretreatment tumors was evaluated using the 22C3, 28-8, and SP142 assays in all patients.

Results

The PD-L1 level in tumor cells determined using the 22C3 assay was the highest among the three assays performed with different antibodies. According to the 22C3 assay results, the PD-L1 tumor proportion score greater than or equal to 50% group had a significantly longer progression-free survival period than the PD-L1 tumor proportion score less than 50% group. Nevertheless, the other assays did not reveal remarkable differences in the objective response rate or progression-free survival.

Conclusions

In our study, PD-L1 expression determined using the 22C3 assay was more correlated with the therapeutic response of patients with NSCLC treated with combined chemoimmunotherapy than that determined using the 28-8 and SP142 assays. Therefore, the 22C3 assay may be useful for clinical decision-making for patients with NSCLC treated with combined chemoimmunotherapy. Trial registration number: UMIN 000043958.

Introduction

Individuals with a history of smoking and a high risk of lung cancer often have a high prevalence of smoking-related comorbidities. The presence of these comorbidities might alter the benefit-to-harm ratio of lung cancer screening by influencing the risk of complications, quality of life, and competing risks of death. Nevertheless, individuals with chronic diseases are underrepresented in screening clinical trials. In this study, we use microsimulation modeling to determine the impact of chronic diseases on lung cancer benefits and harms.

Methods

We extended a validated lung cancer screening microsimulation model that comprehensively recapitulates an individual’s lung cancer development, progression, detection, follow-up, treatment, and survival. We parameterized the model to reflect the impact of chronic diseases on complications from invasive testing, quality of life, and mortality in individuals in five-year age categories between the ages of 50 and 80 years. Outcomes included life-years (LY) gained per 100,000 in patients with chronic obstructive pulmonary disease, diabetes mellitus, heart disease, and history of stroke compared with screening-eligible individuals without comorbidities.

Results

Among individuals between the ages of 50 and 54 years, we found that the presence of a comorbidity altered the LY gained from screening per 100,000 individuals depending on the comorbidity: 4296 LY with no comorbidities; 3462 LY, 3260 LY, 3031 LY, and 3257 LY with chronic obstructive pulmonary disease, heart disease, diabetes mellitus, and stroke, respectively. We observed greater reductions in LY gained in individuals with two comorbidities; we observed similar patterns for individuals between the ages of 55 and 59 years, 60 and 64 years, 65 and 69 years, 70 and 74 years, and 75 and 80 years.

Conclusions

Comorbidities reduce LY gained from screening per 100,000 compared with no comorbidities, and our results can be used by clinicians when discussing the benefits and harms of screening in their patients with comorbidities.

Lenvatinib, a multitarget tyrosine kinase inhibitor for c-Kit and other kinases, has exhibited promising efficacy in treating advanced or metastatic thymic carcinoma (TC). Here, we present the case of a patient with metastatic TC harboring a KIT exon 11 deletion and amplification. The patient exhibited a remarkable response to lenvatinib but experienced rapid disease progression after discontinuation of lenvatinib, referred to as a “disease flare.” This case report indicates that KIT mutations and amplification can predict lenvatinib response in patients with TC. However, in such cases, there might be a risk of disease flares after lenvatinib discontinuation.