Search

The PACIFIC trial demonstrated that durvalumab therapy following chemoradiation (CRT) was associated with improved overall survival (OS) in patients with stage III non-small cell lung cancer (NSCLC). It is unclear whether the results obtained as part of randomised controlled trials are a reflection of real-world (RW) data. Several questions remain unanswered with regard to RW durvalumab use, such as optimal time to durvalumab initiation, incidence of pneumonitis and response in PD-L1 subgroups.In this multicentre retrospective analysis, 147 patients with stage III NSCLC treated with CRT followed by durvalumab were compared with a historical cohort of 121 patients treated with CRT alone. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test in univariate analysis. Multivariate analysis was performed to evaluate the effect of standard prognostic factors for durvalumab use.Median OS was not reached in the durvalumab group, compared with 26.9 months in the historical group (hazard ratio [HR]: 0.56, 95% confidence interval [CI]: 0.37-0.85, p = 0.001). In the durvalumab group, our data suggest improved 12-month OS in patients with PD-L1 expression ≥50% (100% vs 86%, HR: 0.25, 95% CI: 0.11-0.58, p = 0.007). There was no difference in OS between patients with a PD-L1 expression of 1-49% and patients with PD-L1 expression1%. Delay in durvalumab initiation beyond 42 days did not impact OS. Incidence of pneumonitis was similar in the durvalumab and historical groups. In the durvalumab group, patients who experienced any-grade pneumonitis had a lower 12-month OS than patients without pneumonitis (85% vs 95%, respectively; HR: 3.3, 95% CI: 1.2-9.0, p = 0.006).This multicentre analysis suggests that PD-L1 expression ≥50% was associated with favourable OS in patients with stage III NSCLC treated with durvalumab after CRT, whereas the presence of pneumonitis represented a negative prognostic factor.

Introduction The association of venous thromboembolic events (VTE) and lung cancer is highly prevalent. Additionally, the occurrence of a VTE with cancer has been associated with a worse prognosis and a poor quality of life. Underlying cancer biological features such as tumour mutations may contribute to VTE risk and cancer prognosis. Since preclinical data suggest a link between thrombosis and KRAS mutations in tumours, we aimed to validate this association in a patient registry cohort. Methods: A retrospective case control study was performed using the CHUM NSCLC registry. Cases had VTE occurring 6 months previous to or after a diagnosis of NSCLC. Diagnosis of VTE (venous thrombosis, pulmonary embolism, and migratory superficial thrombophlebitis) was confirmed by a review of the imaging reports. Controls were patients with NSCLC without thrombosis matched for age and stage (I-IIIA/IIIB-IV). Exclusion criteria included insufficient tissue for KRAS/EGFR mutation analysis or insufficient clinical information. Results Between Jan 2000 and Dec 2009 a total of 57 cases with VTE and 102 controls without VTE were included. The OR for thrombosis in KRAS and EGFR mutated NSCLC patients are respectively 2.67 (1.12-6.42; p = 0.014) and 0.99 (0.27-3.48; p = 0.99). Conclusions KRAS mutation is associated with an increased risk of VTE in this NSCLC cohort. These findings are consistent with preclinical studies. Prospective data on VTE rates from clinical trials with molecularly defined NSCLC are needed to confirm these findings.

IntroductionBR.21 demonstrated significant survival benefit for non-small cell lung cancer patients receiving erlotinib compared with placebo. We undertook to characterize, by exploratory subset analysis, patients less likely to benefit from erlotinib.MethodsUsing stratification and potential prognostic factors, Cox regression with stepwise selection with minimum Akaike Information Criteria was used to separate erlotinib patients into risk categories based on 10th, 50th, and 90th percentiles of prognostic index scores. The hypothesis was that characteristics of treated patients in the highest risk group would be predictive of lack of benefit from erlotinib when comparing erlotinib to placebo patients in the same risk group.ResultsTen factors (smoking history, performance status, weight loss, anemia, lactic dehydrogenase, response to prior chemotherapy, time from diagnosis, number of prior regimens, epidermal growth factor receptor copy, and ethnicity) were predictive of overall survival for erlotinib-treated patients and were used in the final model. Four risk groups were derived from the index score of the Prognostic Model: Low Risk (HR = 0.34, p < 0.001), Intermediate Low and Intermediate High Risk (HR 0.76, p = 0.05; HR 0.92; p = 0.51) and High Risk (HR 1.07; p = 0.78). Median survivals for erlotinib (placebo) patients in each group were 20.6 (8.9), 10.4 (7.6), 4.0 (4.1), 1.9 (2.3) months. The trend test showed that higher risk was associated with shorter survival (p < 0.001) and less treatment effect (p = 0.03).ConclusionsBy establishing a prognostic model, we identified a small group of patients who did not seem to benefit from erlotinib in this study. This model requires prospective validation to confirm that it is both prognostic and predictive of outcome.