BACKGROUND:NSCLC with mutations of the KRAS or EGFR gene is associated with a high risk of brain metastases (BRA). There are few data on the prevalence and pattern of BRA and on survival in unselected KRAS or EGFR patients. METHODS:This real-world analysis (KOMPASS-study) included 326 NSCLC patients with stage IV adenocarcinoma and either KRAS mutation (n = 90), EGFR mutation (n = 87), or no known driver mutation (n = 149). Prevalence, number, and size of BRA, and the effect of BRA on overall survival (OS) were analyzed. RESULTS:The prevalence of BRA was higher in KRAS patients (40 %) or EGFR patients (39 %) than in no-driver patients (27 %). KRAS patients and no-driver patients significantly more often had single BRA, whereas EGFR patients had multiple BRA (median number 1, 2, and 4, respectively). The presence of BRA did not adversely affect OS in KRAS patients (22.3 vs. 19.2 months, HR 0.91) and no-driver patients (8.9 vs. 10.9 months, HR 0.99). EGFR patients with BRA had inferior OS (20.5 vs. 35.5 months, HR 2.70, p = 0.0004). Patients with single BRA had improved OS (22.3 vs. 13.2 months, p = 0.013). CONCLUSIONS:The lack of a negative effect of BRA on OS in KRAS patients or no-driver patients may be due to the frequent finding of a single BRA amenable to ablative treatment. The negative effect of BRA on OS in EGFR patients points to a distinct biology of EGFR-mutated NSCLC leading to a characteristic radiological pattern of multiple BRA which are not amenable to ablative treatment.

Background: Treatment of lung adenocarcinoma has changed and now includes checkpoint inhibitors (CPIs) or, in the case of an EGFR mutation, third-generation EGFR TKI osimertinib. Few data compare the long-term overall survival (OS) of current and historic subgroups. Methods: This real-world analysis (KOMPASS study) included stage IV lung-adenocarcinoma patients with either EGFR, KRAS, or no mutation. Patients were assigned to the “current” EGFR, KRAS, or no-mutation cohort if they had mutation testing using NGS (n = 199; median date of diagnosis 2021). If they had an EGFR PCR test only, they were assigned to the “historic” EGFR or no-mutation cohort (n = 127; median date of diagnosis 2014). Results: Both the current and the historic EGFR cohorts had significantly longer OS than the respective no-mutation cohorts (HR 0.58 and 0.60, respectively). The current no-mutation and EGFR cohorts had a strong trend to longer OS than the respective historic cohorts. In the no-mutation cohorts, the improvement was due to an increase in long-term survivors (HR 0.71), whereas in the EGFR mutation cohorts, the median OS was improved without long-term survivors (HR 0.70). The KRAS cohort showed OS like the no-mutation cohort, with a plateau of long-term survivors around 20%. Conclusions: A comparison of our data with that of the phase III trials KEYNOTE-189 and FLAURA suggests that the improved outcomes are due to the use of CPIs or osimertinib. The clinical trial results are well translated into real-world clinical practice with comparable OS. KRAS patients benefit from CPI treatment like no-mutation patients.

Recent trials of IO prior to resection in locally advanced resectable NSCLC report high rates of pathological response and promising survival. However, primarily irresectable patients were excluded. Moreover, there is no data on CRT after IO in patients who are primarily not amenable to CRT. We hypothesized that induction IO may enable NSCLC patients with a potentially curative stage including oligometastatic disease (II – IVB [M1b]), for whom primary curative treatment (resection or CRT) is not possible for anatomical or functional reasons, to receive curative treatment. We enrolled 59 NSCLC patients with aforementioned characteristics into a prospective real-world cohort of induction IO followed by morphologic and metabolic reassessment and multidisciplinary board-guided curative treatment (resection [preferred] or CRT) or palliative therapy. Primary endpoint was the proportion of patients receiving curative treatment, secondary endpoints included event-free survival (EFS) and overall survival (OS). Results of the first 35 patients have been published recently (KOMPASS-neo trial, Eur J Cancer (2021) 156:175). There was no funding. 56 patients (95%) received curative treatment (23 R0 resections, 33 CRT). Of the completely resected patients, 11 had a major pathological response, including 9 with a pathological complete response. There were 23 recurrences: 3 (13%) in resected patients, 17 (52%) in CRT-patients, and 3 (100%) in palliative patients (FU 15 months). 21 deaths occurred (15 tumor-related deaths: 12 in CRT patients, and 3 in palliative patients; 2 treatment-related deaths (1 peri-operative, 1 RT pneumonitis); 4 other causes). 18-months OS and EFS were both 91% in the resection cohort compared to 66% and 49% in the RCT cohort. In localized or oligometastatic NSCLC without a primary curative option, induction IO results in a high rate of curative treatment with promising early survival data. Resected patients achieved a high rate of prognostically favorable pathological response.

BACKGROUND:Recent phase II-III trials of immuno(chemo)therapy before resection in locally advanced resectable non-small cell lung cancer (NSCLC) report high rates of pathological response and promising survival. However, primarily, patients who did not undergo resection were excluded from these studies. Moreover, there are no data on chemoradiotherapy (CRT) after immuno(chemo)therapy in patients who are primarily not amenable to CRT. We hypothesised that induction immuno(chemo)therapy may enable patients with NSCLC with a potentially curative stage (III-IVA), for whom primary curative treatment (either resection or CRT) is not possible for anatomical or functional reasons, to receive curative treatment. PATIENTS AND METHODS:We enrolled 35 patients with NSCLC with aforementioned characteristics into a prospective real-world trial of induction immuno(chemo)therapy followed by morphologic and metabolic reassessment and multidisciplinary board-guided curative treatment (resection [preferred] or CRT) or palliative therapy. The primary end-point was the proportion of patients receiving curative treatment. RESULTS:Thirty-two patients (91%) received curative treatment (11 resections and 21 CRT). 73% and 64% of patients who underwent resection had a major or complete pathological response, respectively. There were 14 recurrences: 2 (18%) in patients who underwent resection, 9 (43%) in patients who received CRT and 3 (100%) in patients who received palliative therapy (median follow-up 17 months). Eight tumour-related deaths occurred: 5 (24%) in patients who received CRT; and 3 (100%) in patients who received palliative therapy. There were no treatment-related deaths. CONCLUSIONS:In locally advanced or oligometastatic NSCLC without a primary curative option, induction immuno(chemo)therapy results in a high rate of curative treatment with promising early survival data. patients who underwent resection achieved a high rate of prognostically favourable pathological response.

BACKGROUND:Immuno-oncological (IO) therapies such as PD-1 and PD-L1 antibodies have been introduced in the treatment of advanced non-small cell lung cancer (NSCLC) since 2015 based on randomized trials showing unprecedented advantages in overall survival (OS) with hazard ratios (HRs) between 0.5 and 0.7. The impact of these treatments on OS in routine clinical practice and the role of tumor mass have not been studied.METHODS:557 consecutive patients with inoperable stage III or stage IV NSCLC diagnosed in our certified lung cancer center from 2006 to 2018 were included if they had received at least one line of systemic treatment. OS of immuno-oncologically treated patients (IO patients, n = 144) who received treatment with a PD-1 antibody (nivolumab [n = 77] or pembrolizumab [n = 51]) or a PD-L1 antibody (atezolizumab [n = 4] or durvalumab [n = 12]) was compared to historic controls treated before availability of IO treatment (n = 413) using case-control analysis. IO patients and historic controls were individually matched for stage, performance state, histology, smoking status, gender, age, and initial treatment mode (palliative vs. definitive radio-chemotherapy).RESULTS:Case-control analysis of 91 matched pairs showed significantly longer OS in IO patients compared to historic controls (21.2 vs. 10.9 months, HR 0.526, CI 0.373-0.723). The benefit was more pronounced in patients with lower tumor stage (HR 0.48 [stage III], 0.40 [IVA], 0.63 [IVB]) or smaller tumor size (HR 0.38 [RECIST ≤57 mm], 0.40 [RECIST 58-94 mm], 0.59 [RECIST 95-141 mm], 0.75 [RECIST ≥142 mm]).CONCLUSIONS:IO patients showed significant benefit in OS with HRs comparable to those reported in phase III trials. The benefit tended to be greater in patients with lower tumor mass.

Patients with non-small cell lung cancer (NSCLC) and a prior or synchronous second malignancy are generally excluded from clinical trials. Therefore, little is known on prevalence and prognosis of these patients.