Durvalumab for Stage III EGFR-Mutated NSCLC After Definitive Chemoradiotherapy.

INTRODUCTION: In 2018, durvalumab was approved by the U.S. Food and Drug Administration as consolidation immunotherapy for patients with stage III NSCLC after definitive chemoradiotherapy (CRT). However, whether durvalumab benefits patients with EGFR-mutated NSCLC remains unknown. METHODS: We conducted a multi-institutional retrospective analysis of patients with unresectable stage III EGFR-mutated NSCLC who completed concurrent CRT. Kaplan-Meier analyses evaluated progression-free survival (PFS) between patients who completed CRT with or without durvalumab. RESULTS: Among 37 patients, 13 initiated durvalumab a median of 20 days after CRT completion. Two patients completed 12 months of treatment, with five patients discontinuing durvalumab owing to progression and five owing to immune-related adverse events (irAEs). Of 24 patients who completed CRT without durvalumab, 16 completed CRT alone and eight completed CRT with induction or consolidation EGFR tyrosine kinase inhibitors (TKIs). Median PFS was 10.3 months in patients who received CRT and durvalumab versus 6.9 months with CRT alone (log-rank p = 0.993). CRT and EGFR TKI was associated with a significantly longer median PFS (26.1 mo) compared with CRT and durvalumab or CRT alone (log-rank p = 0.023). Six patients treated with durvalumab initiated EGFR TKIs after recurrence, with one developing grade 4 pneumonitis on osimertinib. CONCLUSIONS: In this study, patients with EGFR-mutated NSCLC did not benefit with consolidation durvalumab and experienced a high frequency of irAEs. Patients who initiate osimertinib after durvalumab may be susceptible to incident irAEs. Consolidation durvalumab should be approached with caution in this setting and concurrent CRT with induction or consolidation EGFR TKIs further investigated as definitive treatment.

Correction to: Community Low-Dose CT Lung Cancer Screening: A Prospective Cohort Study.

The original version of this article contained an error in the usage of the term "false positive rate". The intention of the authors in those instances was simply to compare the absolute percentage of false positive results in the study vs the NLST, not to make any observations about false positive rate in the strict statistical sense (i.e. Type I error probability).

Community low-dose CT lung cancer screening: a prospective cohort study.

BACKGROUND: The National Lung Screening Trial (NLST) in 2011 showed that low-dose CT (LDCT) screening in high-risk groups reduces lung cancer deaths. Major professional organizations, as well as the U.S. Preventative Services Task Force, have endorsed LDCT screening in these select populations. However, major questions remain about whether widespread deployment of CT screening can achieve results similar to the NLST, especially in the community setting. METHODS: A prospective cohort study was initiated in November 2010. Participants at least 50 years old and with at least 20 pack-years of smoking history underwent LDCT screening in a community setting. RESULTS: One hundred and fifty four participants underwent LDCT screening with median follow-up of 2.7 years. Compared with the NLST, there was a higher rate of positive screening tests (35.7 vs. 27.3 %), higher false positive rate (100 vs. 96.4 %), and poor adherence (43 vs. 95 %). Invasive diagnostic follow-up was uncommon and uncomplicated. No interval lung cancer was detected. Late follow-up was mostly attributed to participant or primary care provider preference (67.5 %), participants lost to follow-up (17.5 %), and lack of insurance (10 %). CONCLUSIONS: These findings highlight the potential challenges of generalizing the NLST mortality benefits in the broad deployment of CT screening. Our results support current recommendations that LDCT screening be performed in a highly structured and integrated setting.

A phase I trial of vandetanib combined with capecitabine, oxaliplatin and bevacizumab for the first-line treatment of metastatic colorectal cancer.

BACKGROUND: Vandetanib is a tyrosine kinase inhibitor of both the vascular endothelial growth factor (VEGFR) and epidermal growth factor (EGFR) receptors. The primary objectives of this study were to determine the maximum tolerated dose of vandetanib with capecitabine and oxaliplatin, without and with bevacizumab, for the first line treatment of metastatic colorectal cancer (mCRC), and to define the dose limiting toxicities. MATERIALS AND METHODS: Three cohorts of patients were studied, with capecitabine at 1,000 mg/m(2) twice daily p.o. on days 1-14 of a 3 week cycle, with oxaliplatin i.v. at 130 mg/m(2) on day 1. Vandetanib dosing was 100 mg/day in cohort 1 and 300 mg/day in cohorts 2 and 3. Bevacizumab was added in cohort 3 at 7.5 mg/kg i.v. on day 1 every 3 weeks. RESULTS: Thirteen patients were enrolled and received from one to eight cycles per patient. Grade 4 dermatitis developed in one patient in the first cohort, and the cohort was expanded to six patients with no further dose limiting toxicities (DLT). The second cohort of 3 patients was well tolerated. The third cohort resulted in grade 3 diarrhea, requiring several days of hospitalization and i.v. hydration, in 3 of the 4 patients. Given the severity and duration of diarrhea, each of these was considered a DLT, and therefore cohort 3 was considered to be above the maximum tolerated dose. Six of the 13 patients achieved a partial or complete remission (46%). The time to progression ranged from 2 to 14 months. CONCLUSIONS: Vandetanib at doses of 100 mg and 300 mg daily in combination with capecitabine and oxaliplatin was well tolerated. However, the addition of bevacizumab resulted in severe diarrhea in three out of four patients. Bevacizumab was not well tolerated with vandetanib and XELOX in combination.