Patient-Reported Outcomes From Patients Receiving Immunotherapy or Chemoimmunotherapy for Metastatic Non–Small-Cell Lung Cancer in Clinical Practice

IntroductionImmunotherapy and chemoimmunotherapy clinical trials for metastatic non–small-cell lung cancer (mNSCLC) have generally excluded patients with poor performance status (PS) and have utilized patient-reported measures that could miss some symptoms associated with immunotherapy. The goals of this study were to describe quality of life and symptom burden among mNSCLC patients receiving immunotherapy in clinical practice, and to examine burden by Eastern Cooperative Oncology Group performance status (ECOG PS) and age.Patients and MethodsBetween 2017 and 2018, mNSCLC patients receiving immuno/chemoimmunotherapy at an academic medical center completed the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) and the National Cancer Institute Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Univariate and bivariate analyses described EORTC-QLQ-C30 subscales and the proportion reporting at least moderate PRO-CTCAE symptoms, and compared scores by ECOG PS (0/1 vs. 2/3) and age (< 70 vs. ≥ 70 years).ResultsSixty patients (60% female; 75% < 70 years old; 68% ECOG PS 0/1; 57% receiving single-agent immunotherapy) participated. The mean EORTC-QLQ-C30 global health score was 62.6; EORTC symptoms were highest for fatigue, insomnia, dyspnea, and financial concerns (all > 30). Global health and pain were worse in ECOG PS 2/3 patients. For PRO-CTCAE, 20% to 40% reported at least moderate gastrointestinal, respiratory, dermatologic, arthralgia, or myalgia symptoms. The PRO-CTCAE pain score was higher among ECOG PS 2/3 patients.ConclusionIn clinical practice, global health was largely comparable to published clinical trials, but PRO-CTCAE items indicated a higher symptom prevalence. Closer monitoring of symptoms is warranted in ECOG PS 2/3 patients.     

Immunotherapy Treatment Patterns and Outcomes Among ALK-Positive Patients With Non–Small-Cell Lung Cancer

IntroductionThe treatment landscape for anaplastic lymphoma kinase (ALK)-positive non–small-cell lung cancer (NSCLC) primarily involves ALK-directed tyrosine kinase inhibitors (TKIs). Although therapy with immune checkpoint inhibitors (ICIs) is a treatment option in NSCLC, the efficacy of ICI is inconclusive in ALK-positive NSCLC as a result of limited data. This retrospective real-world study sought to describe the characteristics of ALK-positive NSCLC patients treated with ICI and to assesses treatment outcomes in US oncology practices.Patients and MethodsThis analysis used the Flatiron Health electronic health record–derived deidentified database and included adult (18 years and older) ALK-positive advanced NSCLC patients with receipt of one or more ICIs after January 1, 2015. Median time to ICI discontinuation and real-world progression-free survival (rwPFS) were estimated by Kaplan-Meier methods.ResultsOf 83 patients with ALK-positive NSCLC treated with ICIs, 50.6% (n = 42) received ICI without a prior ALK TKI. Median time to ICI discontinuation was 2.17 months (95% confidence interval, 1.41, 3.32). The median rwPFS was 2.34 months (95% confidence interval, 1.55, 3.09); in patients who received an ICI without prior ALK TKI, it was 3.9 months, and in patients who received ICI therapy after an ALK TKI, it was 1.5 months.ConclusionsReal-world effectiveness (rwPFS) of ICIs in ALK-positive NSCLC patients, whether provided before or after TKIs, was limited, underscoring the relative lack of efficacy of ICI in this patient population, particularly compared to approved ALK TKIs.     

Clinical and Imaging Features of Non–Small-Cell Lung Cancer in Young Patients

BackgroundNon–small-cell lung cancer (NSCLC) in young adult patients is rare, with scarce data available in patients aged < 40 years and even less in those aged < 35 years. Our goal was to determine the presenting symptoms, clinicopathologic characteristics, and imaging features of young patients with NSCLC at time of diagnosis and compare them to those of older adults.Patients and MethodsWe retrospectively analyzed the medical records and imaging of young patients (≤ 40 years old) with NSCLC treated at our institution between 1998 and 2018. Patients < 35 years old were compared to those between 35 and 40 years old. Characteristics of patients ≤ 40 years old were compared to older patients (> 40 years) from publicly available data sets.ResultsWe identified 166 young patients with NSCLC (median age, 36.6 years; range, 18-40 years). Most presented with nonspecific respiratory symptoms and were diagnosed with pneumonia (84/136, 62%). Compared to patients < 35 years old, patients 35-40 years old were more likely to have malignancy detected incidentally (15% vs. 5%, P = .04). Patients < 35 years old were more likely to have central tumors (55% vs. 33%, P = .02) and to have bone (38% vs. 19%, P = .007) and lung (39% vs. 24%, P = .03) metastases. Compared to older patients (> 40 years), young patients were more likely to be never smokers (65.0% vs. 14.7%, P < .001) and to have advanced disease (88% vs. 66%, P < .001).ConclusionYoung patients with NSCLC often present with nonspecific symptoms and have advanced disease at diagnosis, often mimicking other pathologies. Awareness of the clinical presentation and imaging features of NSCLC in young patients may help minimize delays in diagnoses.     

Brain Metastases in Non–Small-Cell Lung Cancer

Up to 50% of patients with advanced non-small-cell lung cancer will develop brain metastases at some point during their illness. These metastases cause a substantial burden in morbidity and mortality, which has motivated research and technological innovation over the past 2 decades. Surgery, radiotherapy, and systemic therapies have each played a role in management, with the greatest changes associated with the popularization of stereotactic radiosurgery. In this review, the evidence behind each modality used in the management of brain metastases for non–small-cell lung cancer patients is examined, and recommendations regarding the current standards of care and areas of future research focus are provided.     

A Phase I Study of Temsirolimus and Thoracic Radiation in Non–Small-Cell Lung Cancer

BackgroundThe addition of targeted agents to thoracic radiation has not improved outcomes in patients with locally advanced non–small-cell lung cancer (NSCLC). To improve cure rates in locally advanced NSCLC, effective targeted therapies need to be identified that can be given safely with radiation therapy. Temsirolimus is an inhibitor of the mammalian target of rapamycin (mTOR) pathway and has single-agent activity in lung cancer. Inhibition of the mTOR pathway has been found to augment the cytotoxic effect of radiation in preclinical studies. There is scant clinical experience with mTOR inhibitors and radiation.Patients and MethodsThis was a phase I study evaluating the combination of temsirolimus with thoracic radiation in patients with NSCLC.ResultsTen patients were enrolled in the study. The dose-limiting toxicities included sudden death, pneumonitis, and pulmonary hemorrhage. The maximum tolerated dose of temsirolimus that could be administered safely with concurrent radiotherapy (35 Gy in 14 daily fractions) was 15 mg intravenously weekly. Of the 8 evaluable patients, 3 had a partial response and 2 had stable disease.ConclusionThe combination of temsirolimus 15 mg weekly and thoracic radiation is well tolerated and warrants further investigation, perhaps in a molecularly defined subset of patients.     

Performance Status and Age as Predictors of Immunotherapy Outcomes in Advanced Non–Small-Cell Lung Cancer

IntroductionImmunotherapy has become a key treatment for patients with advanced non–small-cell lung cancer (NSCLC). While a survival advantage has been proven for patients who are medically fit, it is unknown whether a benefit exists for patients with poor performance status (PS).Patients and MethodsWe performed a retrospective analysis of NSCLC patients who received immunotherapy in our health system. Age and PS at the time of initial immunotherapy administration were assigned based on physician documentation. Radiographic response and date of progression were assigned according to the treating physician’s assessment and confirmed by the study team. Immune-related adverse events were extracted from records.ResultsWe identified 285 NSCLC patients who received immunotherapy between January 2014 and April 2018. In this group, 153 patients (53.7%) had PS 0-1, 114 (40.0%) had PS 2, and 18 (6.3%) had PS 3. Response rates were similar across PS groups with 26.6% for PS 1, 25.2% for PS 2, and 23.1% for PS 3 (P = .95). Survival outcomes varied with pretreatment PS. For PS 0-1, PS 2, and PS 3, median overall survival was 14.7, 8.3, and 1.5 months (P < .001), and progression-free survival was 7.4, 5.1, and 1.3 months (P < .001). Patients aged < 70 had a lower rate (7.6%) of immune-related adverse events requiring steroids compared to patients ≥ 70 (15%) (P = .04).ConclusionPatients with poor baseline PS demonstrate similar response rate but inferior progression-free survival and overall survival compared to medically fit patients. Prospective trials are needed to optimize treatment for this large population.     

First Clinical Report of Proton Beam Therapy for Postoperative Radiotherapy for Non–Small-Cell Lung Cancer

Background and Purpose

The characteristic Bragg peak of proton beam therapy (PBT) allows for sparing normal tissues beyond the tumor volume that may allow for decreased toxicities associated with postoperative radiation therapy (PORT). Here we report the first institutional experience with proton therapy for PORT in patients with non–small-cell lung cancer (NSCLC) and assess early toxicities and outcomes.

Clinical Characteristics and Prognosis of Patients With Advanced Non–Small-cell Lung Cancer Who Are Ineligible for Clinical Trials

Background

Most patients with non–small-cell lung cancer (NSCLC) are ineligible for clinical trials. However, few studies have reported on the profiles and treatment outcomes for these patients. Therefore, we investigated the characteristics, outcomes, and survival of patients with advanced NSCLC who were ineligible for clinical trials.

Node-Positive Segmentectomy for Non–Small-Cell Lung Cancer: Risk Factors and Outcomes

BackgroundSegmentectomy for well-selected early stage non–small-cell lung carcinoma (NSCLC) has been shown to have similar oncologic outcomes and survival to lobectomy. However, these data are based on the presumption that the disease is node negative. Few data exist regarding the risk factors for and the outcomes of patients with disease treated with segmentectomy that is found to be node positive. We sought to determine the risk factors for and outcomes of clinical stage I NSCLC patients who are treated with segmentectomy but are determined to be node positive.Patients and MethodsWe queried patients with clinical stage I NSCLC ≤ 3 cm within the National Cancer Data Base between 2004 and 2014 who were treated with segmentectomy or lobectomy and found to have positive nodes. Kaplan-Meier curves with log-rank tests were used to compare overall survival (OS) between segmentectomy and lobectomy. For comparison only, segmentectomy patients with pathologically node-negative disease were identified to determine predictors of node positivity after segmentectomy via multivariable logistic regression.ResultsA total of 4556 patients with node-positive disease were identified, comprising 115 segmentectomy patients and 4441 lobectomy patients. Multivariable analysis identified increasing tumor size, squamous-cell histology, and increasing number lymph nodes sampled as significant predictors of node positivity after segmentectomy. There was no difference in OS between segmentectomy and lobectomy, with 3-year OS rates of 66.3% and 68.1%, respectively (P = .723).ConclusionThere are discrete risk factors for discovering positive nodes after segmentectomy. Segmentectomy is associated with similar OS compared to lobectomy for clinical stage I NSCLC found to be node positive.