9078 Background: ROS1 rearrangements are found in approximately 1% of non-small cell lung cancer (NSCLC) patients. Prospective clinical trials showed high efficacy of crizotinib in this molecular subset. Lately, we reported an overall response rate (ORR) of 70% and a median progression-free survival (PFS) of 19.4 months for patients treated within the EUCROSS trial (Michels et al. Clin Oncol, 37(15_suppl):9066-9066, 2019). Here we present an updated analysis of the overall survival. Methods: EUCROSS is a European multi-centre, single arm phase 2 trial (Clinicaltrial.gov identifier: NCT02183870). Key eligibility criteria were ≥18 years of age, advanced/metastatic lung cancer, centrally confirmed ROS1-rearranged (fluorescence-in situ hybridisation) and no or stable brain metastases at baseline. Crizotinib was given at a dose of 250 mg twice daily. Primary endpoint of the trial was investigator-assessed ORR in the response-evaluable population (Response Evaluation Criteria in Solid Tumors, version 1.1), with secondary endpoints of PFS and overall survival (OS). Results: Of the 34 patients who received at least one dose of crizotinib (intention-to-treat population, ITT), 30 were included the primary efficacy analysis set (PAS). After a median follow-up of 55.9 months, 13 (43%) patients in the PAS and 15 (44%) in the ITT had died. Median OS was not reached in either group (95% CI, 17.1-NR and 20.3-NR, respectively). OS was negatively correlated with the presence of brain metastases (Log-rank p = 0.1805) and TP53 mutations (Log-rank p = 0.015). Detailed listings of the survival rates are depicted in Table. No new safety signals were observed. Owing to the approval of crizotinib by the European Medicines Agency, all patients who were still on treatment by January 24 th 2018 (n=8), were prescribed crizotinib outside the trial. Conclusions: Updated OS highlights the efficacy of crizotinib in patients with ROS1-rearranged lung cancer. Patients with co-occurring TP53 mutations or brain metastases had worse outcomes and represent challenging populations. Clinical trial information: NCT02183870. [Table: see text]
Purpose To investigate a new effective, nonleukemogenic polychemotherapy regimen, BAGCOPP (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, gemcitabine) in a phase I/II dose-escalation study in patients with advanced-stage Hodgkin's disease (HD). Patients and Methods Patients in clinical stages IIB with risk factors III and IV were enrolled in this nonrandomized, multicenter trial aimed at defining the maximum-tolerated dose of gemcitabine within a modified escalated BEACOPP regimen. Gemcitabine was given at a starting dose of 800 mg/m 2 on days 1 and 4 of each cycle. Results Twenty-seven patients (eight female, 19 male) were enrolled with a median age of 33 years (range, 19 to 65 years). Due to a higher than expected hematotoxicity, the day-4 application of gemcitabine was omitted after 14 patients were included and 59 cycles were given. A total of eight patients developed lung toxicity, mainly pneumonitis (six of eight), which led to the termination of the study. With a median follow-up of 27 months, 25 patients are in continuing complete remission. Conclusion The substitution of etoposide by gemcitabine in the escalated BEACOPP schema is not feasible and leads to severe pulmonary toxicity. This toxicity is probably related to the concomittant application of gemcitabine and bleomycin.
The purpose of this study was to evaluate the relevance for the prediction of clinical benefit of first-line treatment with erlotinib using different quantitative parameters for PET with both 18F-FDG and 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) in patients with advanced non–small cell lung cancer. Methods: Data were used from a prospective trial involving patients with untreated stage IV non–small cell lung cancer. 18F-FDG PET and 18F-FLT PET were performed before and 1 (early) and 6 (late) weeks after erlotinib treatment. Several quantitative standardized uptake values (SUVs) using different definitions of volumes of interest with varying isocontours (maximum SUV [SUVmax], 2-dimensional peak SUV [SUV2Dpeak], 3-dimensional [3D] peak SUV [SUV3Dpeak], 3D isocontour at 50% of the maximum pixel value [SUV50], 3D isocontour at 50% adapted for background [SUVA50], 3D isocontour at 41% of the maximum pixel value adapted for background [SUVA41], 3D isocontour at 70% of the maximum pixel value [SUV70], 3D isocontour at 70% adapted for background [SUVA70], and relative SUV threshold level [SUVRTL]) and metabolically active volume measurements were obtained in the hottest single tumor lesion and in the sum of up to 5 lesions per scan in 30 patients. Metabolic response was defined as a minimum reduction of 30% in each of the different SUVs and as a minimum reduction of 45% in metabolically active volume. Progression-free survival (PFS) was compared between patients with and without metabolic response measured with each of the different parameters, using Kaplan–Meier statistics and a log-rank test. Results: Patients with a metabolic response on early 18F-FDG PET and 18F-FLT PET in the hottest single tumor lesion as well as in the sum of up to 5 lesions per scan had a significantly longer PFS, regardless of the method used to calculate SUV. However, the highest significance was obtained for SUVmax, SUV50, SUVA50, and SUVA41. Patients with a metabolic response measured by SUVmax and SUV3Dpeak on late 18F-FDG PET in the hottest single tumor lesion had a significantly longer PFS. Furthermore, Kaplan–Meier analyses showed a strong association between PFS and response seen by metabolically active volume, measured either in early 18F-FLT or in late 18F-FDG. Conclusion: Early 18F-FDG PET and 18F-FLT PET can predict PFS regardless of the method used for SUV calculation. However, SUVmax, SUV50, SUVA50, and SUVA41 measured with 18F-FDG might be the best robust SUV to use for early response prediction. Metabolically active volume measurement in early 18F-FLT PET and late 18F-FDG PET may have an additional predictive value in monitoring response in patients with advanced non–small cell lung cancer treated with erlotinib.
