Journal of Thoracic Oncology最新文献

Objectives: To evaluate how comorbidities affect mortality benefits of lung cancer screening (LCS) with low-dose computed tomography.

Methods: We developed a comorbidity index (Prostate, Lung, Colorectal, and Ovarian comorbidity index [PLCO-ci]) using LCS-eligible participants' data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial (training set) and the National Lung Screening Trial (NLST) (validation set). PLCO-ci predicts five-year non-lung cancer (LC) mortality using a regularized Cox model; with performance evaluated using the area under the receiver operating characteristics curve. In NLST, LC mortality (per original publication) was compared between low-dose computed tomography and chest radiograph arms across the PLCO-ci quintile (Q1-5) using a cause-specific hazard ratio (csHR) with 95% confidence intervals (CIs).

Results: Analyses included 34,690 PLCO and 53,452 NLST participants (mean age: 62 y [±5 y] and 61 y [±5 y], 58% and 59% male individuals, and 39% and 41% active smokers, respectively). PLCO-ci predicted five-year non-LC mortality with an area under the receiver operating characteristics curve of 0.72 (95% CI: 0.71-0.74) in PLCO and 0.69 (95% CI: 0.67-0.70) in NLST. In NLST, at a median follow-up of 6.5 years, LC mortality was significantly reduced for participants with intermediate comorbidity (Q2, Q3, and Q4): csHR 0.62 (95% CI: 0.41-0.95), 0.68 (95% CI: 0.48-0.96), and 0.72 (95% CI: 0.54-0.96) respectively, with a nonstatistically significant reduction for Q1 (csHR = 0.72, 95% CI: 0.45-1.17) and no reduction for Q5 participants (csHR = 0.99, 95% CI: 0.79-1.23). Participants in Q2, Q3, and Q4 (60%) accounted for 89% of LC deaths averted among all NLST participants. Q1 participants had low LC incidence, whereas Q5 had higher localized LC lethality, more squamous cell carcinomas, and untreated LC.

Conclusions: The PLCO-ci developed in this work shows that individuals with intermediate comorbidity benefited the most from LCS, highlighting the need of addressing comorbidities to achieve LC mortality benefits.

Introduction: Osimertinib is the first-line treatment for patients with NSCLC who have EGFR mutations and favorable performance status (PS). Despite the increasing clinical data on osimertinib, evidence for its use in patients with impaired PS remains limited. Therefore, a multicenter phase II trial (OPEN/TORG2040) was conducted to evaluate the efficacy and safety of first-line osimertinib treatment in patients with EGFR mutation-positive NSCLC and a poor PS.

Methods: Patients with previously untreated advanced NSCLC harboring EGFR-sensitizing mutations and PS of 2 to 4 were enrolled. Osimertinib (80 mg once daily) was orally administered to eligible patients. The primary end point was objective response rate. The secondary end points were disease control rate, PS improvement rate, patient-reported outcomes, and safety.

Results: Between February 2021 and February 2022, 30 patients with poor PS (22 with a PS of 2, six with a PS of 3, and two with a PS of 4) were enrolled. The median age was 75 (range, 41-92) years, and 18 patients had brain metastases. The objective response rate was 63.3% (90% confidence interval, 46.7%-77.9%; one-sided, p = 0.033). Disease control and PS improvement rates were 93.3% and 63.3%, respectively. Global health status/QoL also improved. Median progression-free and overall survival were 8.0 and 25.4 months, respectively. Eight patients (26.7%) experienced serious adverse events leading to discontinuation, and six (20.0%) experienced interstitial lung disease.

Conclusions: This prospective study confirmed the efficacy of first-line osimertinib treatment in patients with EGFR mutation-positive NSCLC and poor PS, highlighting the need for interstitial lung disease risk management.

Trial registration number: Japan Registry of Clinical Trials Identifier: jRCTs041200100.

Introduction: Treatment options for patients with EGFR-mutated NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy are limited.

Methods: CHRYSALIS-2 cohort A evaluated amivantamab plus lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on or after osimertinib and platinum-based chemotherapy. Primary end point was investigator-assessed objective response rate (ORR). The patients received 1050 mg of intravenous amivantamab (1400 mg if ≥ 80 kg) plus 240 mg of oral lazertinib.

Results: In cohort A (N = 162), the investigator-assessed ORR was 28% (95% confidence interval [CI]: 22-36). The blinded independent central review-assessed ORR was 35% (95% CI: 27-42), with a median duration of response of 8.3 months (95% CI: 6.7-10.9) and a clinical benefit rate of 58% (95% CI: 50-66). At a median follow-up of 12 months, 32 of 56 responders (57%) achieved a duration of response of more than or equal to 6 months. Median progression-free survival by blinded independent central review was 4.5 months (95% CI: 4.1-5.8); median overall survival was 14.8 months (95% CI: 12.2-18.0). Preliminary evidence of central nervous system antitumor activity was reported in seven patients with baseline brain lesions and no previous brain radiation or surgery. Exploratory biomarker analyses using next-generation sequencing of circulating tumor DNA revealed responses in patients with and without EGFR- or MET-dependent resistance. The most frequent adverse events were rash (grouped term; 81%), infusion-related reaction (68%), and paronychia (52%). The most common grade greater than or equal to 3 treatment-related adverse events were rash (grouped term; 10%), infusion-related reaction (9%), and hypoalbuminemia (6%).

Conclusions: For patients with limited treatment options, amivantamab plus lazertinib demonstrated an antitumor activity with a safety profile characterized by EGFR- or MET-related adverse events, which were generally manageable.

Introduction: The phase 2 TROPiCS-03 study evaluated the efficacy/safety of sacituzumab govitecan (SG) as second-line treatment in patients with previously treated extensive-stage SCLC (ES-SCLC).

Methods: TROPiCS-03 (NCT03964727) is a multicohort, open-label, phase 2 basket study of solid tumors, including ES-SCLC. Adults with ES-SCLC that progressed after one previous line of platinum-based chemotherapy and anti-programmed death-(ligand) 1 (PD-[L]1) therapy received SG 10 mg/kg on days 1 and 8 of a 21-day cycle. The primary end point was the investigator-assessed objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1. Key secondary end points included investigator-assessed duration of response (DOR) and progression-free survival (PFS); blinded independent central review-assessed ORR, DOR, and PFS; overall survival (OS); and safety. Efficacy was evaluated in patients with platinum-resistant and platinum-sensitive disease.

Results: Among 43 patients (median follow-up, 12.3 [range, 8.1-20.1] mo), investigator-assessed ORR was 41.9% (95% confidence interval [CI]: 27.0%-57.9%), with 18 confirmed partial responses; median (95% CI) DOR, PFS, and OS were 4.73 (3.52-6.70), 4.40 (3.81-6.11), and 13.60 (6.57-14.78) months, respectively. The efficacy results of the blinded independent central review assessments were similar. The investigator-assessed ORR (95% CI) was 35.0% (15.4%-59.2%) in patients with platinum-resistant disease (n = 20) and 47.8% (26.8%-69.4%) in patients with platinum-sensitive disease (n = 23). Furthermore, 32 patients (74.4%) had grade greater than or equal to 3 treatment-emergent adverse events (TEAEs). No TEAE led to SG discontinuation; one treatment-related TEAE (neutropenic sepsis) led to death.

Conclusions: SG has promising efficacy as second-line treatment of ES-SCLC, irrespective of platinum sensitivity. Safety was manageable and consistent with that observed in other SG studies.