Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry.

BACKGROUND: Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction. PATIENTS AND METHODS: We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation. RESULTS: We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2). CONCLUSIONS: : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.

Hospital lung surgery volume and patient outcomes.

OBJECTIVES: There has been evidence of an association between patient outcomes and the number of surgeries performed at a hospital. To our knowledge, there are no Australian data on hospital cancer surgery volumes and patient outcomes. We evaluated the relationship between hospital non-small cell lung cancer (NSCLC) surgery volume and patient outcomes in Victoria. MATERIALS AND METHODS: Patients with a primary diagnosis of NSCLC between 2008 and 2014 were identified in the Victorian Cancer Registry (n = 15,369), 3,420 (22%) of whom had lung cancer surgery. Primary outcome was death within 90 days of surgery and secondary outcomes included overall survival, use of postoperative ventilation and ≥24hours spent in ICU. Hospital volume was measured as the average number of lung surgeries performed per year, with quartiles Q1: 1-17, Q2: 18-34, Q3: 35-58 and Q4: 59 + . RESULTS: 57% (1,941/3,420) lung cancer patients underwent lobectomy, 38% (1,299/3,420) sub-lobar resection and 5% (180/3,420) pneumonectomy. The overall 90-day mortality after lung surgery was 3.5%, and was 2.6% and 4.5% for patients undergoing lobectomy and sub-lobar resection respectively. There was no difference in 90-day mortality and overall survival between low- and high-volume centres regardless of procedure. Patients operated on in lower volume centres had more admissions to ICU ≥24hours (Q1. 55% vs. Q4. 11%, p-trend <0.001). A higher proportion of patients attending private hospitals (19%) had an ASA score of 4 compared with patients attending a public hospital (9%). CONCLUSION: We observed no evidence of survival differences between lung cancer patients attending low- and high-volume hospitals for cancer surgery. A higher proportion of patients had an ICU admission ≥24hours in lower volume centres and there are a higher proportion of patients with an ASA score of 4 in private hospitals compared to public hospitals.