Median Progression-free Survival In Group Research Articles

Secondary cytoreductive surgery followed by olaparib tablets as maintenance therapy in patients with BRCA mutated recurrent ovarian cancer: A multi-center retrospective study

ObjectiveTo evaluate the effect of secondary cytoreductive surgery (SeCRS) followed by platinum-based chemotherapy (PBC) and olaparib tablets as maintenance therapy in patients with BRCA mutated recurrent epithelial ovarian cancer. MethodsThis was a retrospective study of a prospective database. We collected information on 623 patients diagnosed with BRCA mutated recurrent epithelial ovarian cancer, all of whom underwent SeCRS followed by PBC in combination with or without olaparib. Overall survival and progression-free survival were measured to evaluate treatment effectiveness. ResultsOf the 623 patients recruited, 240 underwent SeCRS plus hyperthermic intraperitoneal chemotherapy followed by PBC and olaparib maintenance therapy (Group A), 248 underwent SeCRS followed by PBC and olaparib maintenance therapy (Group B), and 135 underwent SeCRS followed by PBC only upon recurrence (Group C). The median progression-free survival for Group A was significantly longer than that for Group B (32.5 vs. 24.2 months, P<0.001), and Group B was significantly longer than Group C (24.2 vs. 15.1 months, P<0.001). The median overall survival for Groups A was significantly longer than that for Group B (71.4 vs. 63.5 months, P<0.001), and Group B was significantly longer than Group C (63.5 vs. 47.5 months, P<0.001). ConclusionsThis study suggested that SeCRS followed by PBC and olaparib maintenance therapy resulted in longer overall survival and progression-free survival than SeCRS followed by PBC only in patients with BRCA mutated recurrent ovarian cancer, especially in patients treated with SeCRS plus hyperthermic intraperitoneal chemotherapy.

A long-term retrospective cohort-based risk-benefit analysis of augmenting total cumulative I-131 activity to 37GBq in differentiated thyroid cancer patients with skeletal metastases

Objective Skeletal metastases in differentiated thyroid cancer (DTC) patients are associated with poor prognosis. The objective was to determine the maximum I-131 cumulative activity that could be safely administered without compromising efficacy. The secondary objective was to identify other prognostic factors affecting survival outcomes. Materials and methods This was a retrospective cohort study done at a tertiary-care institution comprising of data from January 1990-June 2020. 489 DTC patients having skeletal metastases with ≥12 months follow-up were included. Ninety-six percent of patients had thyroidectomy followed by radioiodine therapy for skeletal metastases. All patients were on oral suppressive levothyroxine tablets. External beam radiotherapy (EBRT) and oral tyrosine kinase inhibitors were used whenever indicated. The main outcome measures were overall survival (OS), progression-free survival (PFS), and adverse-events. Results There were 347 (71%) females and 324 (66%) had follicular carcinoma thyroid. Median follow-up was 78 (interquartile range, IQR: 37–153) months. 333 patients (68%) received ≤37GBq I-131 cumulative activity (group 1) and 156 patients (32%) received &gt;37GBq cumulative RAI activity (group 2). Overall median OS and PFS were 74 (95% confidence interval (CI): 62.2–85.8) and 48 (95%CI: 40.5–55.4) months, respectively. The 5-, 10-, 15- and 20-year estimated overall survival probabilities were 55.7%, 28.4%, 14% and 8.3%, respectively. On multivariate analysis, age(&lt;55years) (p&lt;0.001), female gender(p = 0.01), cumulative I-131 activity &gt;37GBq (p&lt;0.001) and EBRT(p = 0.001) were favourably associated with OS; no factors were significantly associated with PFS. The median OS for groups 1 &amp; 2 were 51 versus 90 months (p&lt;0.001) &amp; median PFS for groups 1 &amp; 2 were 45 versus 53 months respectively (p = 0.9). However, cumulative activity &gt;37GBq resulted in more adverse events (2.4%), particularly bone marrow suppression (3.5%). Conclusion For better survival outcomes, cumulative I-131 activity upto 37GBq could be administered with acceptable toxicity to DTC patients with skeletal metastases.

A retrospective analysis of secondary cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in patients with recurrent ovarian cancer.

To evaluate the effect of secondary cytoreductive surgery (SeCRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer patients. This retrospective study analyzed a prospective database. We collected information of 389 patients who were diagnosed with recurrent epithelial ovarian cancer. All patients underwent SeCRS with or without HIPEC. Overall survival and progression-free survival (PFS) were used to evaluate the treatment effectiveness. Of the 389 patients collected, 123 underwent primary or interval cytoreductive surgery at initial treatment and SeCRS at recurrence (Group A), 130 underwent primary or interval cytoreductive surgery at initial and SeCRS plus HIPEC at recurrence (Group B), and 136 underwent primary or interval cytoreductive surgery plus HIPEC at initial and SeCRS plus HIPEC at recurrence (Group C). The median overall survival for Groups A, B, and C were 49.1 months (95% confidence interval [CI]: 47.6-50.5), 56.0 months (95% CI: 54.2-57.7), and 64.4 months (95% CI: 63.1-65.6), respectively. The median PFS for Groups A, B, and C were 13.1 months (95% CI: 12.6-13.5), 15.0 months (95% CI: 14.2-15.7), and 16.8 months (95% CI: 16.1-17.4), respectively. There were no significant difference in incidence and grade of adverse events among groups. This study suggested that SeCRS plus HIPEC followed by chemotherapy resulted in longer overall survival and PFS than only SeCRS followed by chemotherapy in patients with recurrent ovarian cancer, especially in patients who were treated with repeat HIPEC.

Overall survival and toxicity of Y90 radioembolization for hepatocellular carcinoma patients in Barcelona Clinic Liver Cancer stage C (BCLC-C)

IntroductionNational Comprehensive Cancer Network HCC guidelines recommend Y90 to treat BCLC-C patients only in select cases given the development of systemic regimens. We sought to identify ideal candidates for Y90 by assessing survival and toxicities in this patient group.Materials and methodsThe Radiation-Emitting Selective Internal radiation spheres in Non-resectable tumor registry is a prospective observational study (NCT: 02,685,631). Patients with advanced HCC were stratified into 3 groups based on tumor location, Eastern Cooperative Oncology Group (ECOG) performance status, and liver function. Group 1: liver isolated HCC, ECOG 0 and Child Pugh (CP) A (n = 12, 16%), Group 2: liver isolated HCC, ECOG ≥ 1 or CP B/C (n = 37, 49%), and Group 3: extrahepatic HCC with any ECOG or CP score (n = 26, 35%). Patients in any group could have macrovascular invasion. Overall survival (OS) and progression-free survival (PFS) with 95% confidence intervals (95% CI) were calculated. Grade 3 + toxicities were tracked using Common Terminology Criteria for Adverse Events v5. Cox proportional hazard model was performed to determine factors affecting OS.ResultsSeventy-five BCLC-C patients treated between 2015 and 2019 were reviewed. The groups were similar in age, sex, race, and ethnicity (all p > 0.05). Bilobar disease was least common in Group 1 (p < 0.001). Median OS of the entire cohort was 13.6 (95% CI 7.5–16.1) months. Median OS of Groups 1–3 were 21.8, 13.1 and 11.5 months respectively (p = 0.6). Median PFS for the cohort was 6.3 (4.8–14.7) months. Median PFS for group 1 was not reached. Mean PFS for Group 1 was 17.3 ± 4.8 months. Median PFS for Groups 2 and 3 was 6.8 and 5.9 months (X2 = 1.5, p = 0.5). Twenty-four Grade 3 or greater toxicities developed, most commonly hyperbilirubinemia (8/75, 11%) and thrombocytopenia (2/75, 3%). The incidence of toxicities between groups was similar (all p > 0.05). Cox Proportional Hazard analysis predicted shorter OS with CP class B/C (X2 = 6.7, p = 0.01), while macrovascular invasion (X2 = 0.5, p = 0.5) and ECOG score of ≥ 1 (X2 = 2.1, p = 0.3) was not associated with OS.ConclusionsOS of CPA patients with advanced HCC and performance status of 0 was 21.8 months following Y90. CP A cirrhosis is the best predictor of prolonged OS in advanced (BCLC-C) HCC.

Young Adults with Multiple Myeloma Have Distinct Clinical and Molecular Characteristics Compared to Older Patients

Introduction Multiple Myeloma (MM) is an incurable plasma cell malignancy with a median age of 65 years at diagnosis. Although previous studies in "young” MM have been performed, they focus on the clinical characteristics. Within this study, we aim to understand the clinical characteristics and genomic drivers of young MM using the Weill Cornell/New York Presbyterian (WCM) and CoMMpass (MMRF) registry. Methods Young MM was defined as onset of MM at age <= 45. The WCM MM registry was queried for patient meeting the diagnosis for MM based on International Myeloma Working Group (IMWG). A control population of MM was created by randomly sampling the patients within the registry that were >45 years old. Clinical features and outcomes were recorded for each patient. The MMRF study is an observational international registry of newly diagnosed MM. A total of 1143 patients had clinical data. Baseline demographic, clinical and laboratory data, along with treatment and genomic (whole exome sequencing, RNA sequencing) was collected, and patients were followed prospectively every 6 months. Patients were divided into <= 45-year group and those above the median age in this cohort (>63 year). The primary end point of our analysis was progression free survival (PFS). Kaplan Meier and univariable Cox proportional hazard model was performed. Multivariable Cox model was created based on the results of univariable model. Land-mark analysis was used to control for time-dependent covariates. All analysis was performed using R software, version 4.1 Results The WCM cohort consisted of a total of 179 patients for this study. 61 patients were <= 45 years, and 98 patients belonging to an older control group. The younger-patients group was enriched for individuals of African American descent (40% vs 10%, p = 0.04), stage I ISS (51% vs 34%, p 0.01), more use of autologous stem cell transplant (ASCT), and less frequent prior diagnosis of smoldering myeloma (SM) (2.3% vs 18%, p = 0.017). There was a trend of higher rates of EMD and higher free light chain ratio in the young group, but this was not statistically significant. The median PFS for each group was 7.92 years (95% CI 4.50 - NA) for the younger group and 3.25 years (95% CI 1.92 - 10.67) for the >45-year group. In the univariable model the >45 year had worse PFS (HR 2.4, 95CI 1.2-4.6, p < 0.01). The association of worse PFS in the >45 year group (HR 6.3, 95%CI 2.3-17.2) persisted in the multivariable analysis, in addition to the presence of EMD (HR 3.2, 95% CI 1.4-7.3), and ISS stage (Table 2). In the MMRF registry, 65 and 548 patients <= 45 years and >63 years respectively were identified. The young group had higher proportion of African American (33% vs 15%, p 0.01), lower ISS (stage I 46% vs 31%, p = 0.04), and less frequency of deletion 13q (35% vs 50%, p 0.03) and gain 1q (22% vs 42%, p < 0.01). t(4;14) was seen more frequently in the young group, but this was not statistically significant (18% vs 9%, p = 0.056). DEA and GSEA showed a total of 1945 (3.5%) and 2164 (3.9%) over and under expressed genes, with the young group being enriched for the CD-1 transcriptional signatures (NES 1.86, adjusted p 0.028). There were no differences in the rates of mutation in the top 23 mutated genes in MM. The median PFS for the young group was 5.0 years (95% CI 2.3 - 5.9) vs 5.4 (95% CI 5.4 - 5.8) years, HR 1.56 (95% CI 1.05-2.3, p = 0.02) on the univariable analysis. Conclusions Young patients with MM have distinct clinical and demographic characteristics, including higher rates in African Americans, lower ISS stage, and lower rates of deletion 13q and gain 1q and enrichment in the CD-1 MM signature suggesting a potential role genetic and environmental factors in the early presentation at diagnosis. However, young patients had comparable to improved PFS than older patients that could be attributed to both biologic drivers, or factors related to patient age, such as better performance status, aggressive treatment, and potentially better tolerance leading to more exposure to antimyeloma therapy. The impact of EMD and ISS have been well described in MM, and the presence of EMD in this population remains an important prognostic factor. Lastly, although we used an arbitrary cut-off of 45 years old, we acknowledge this population may well represent biological spectrum of disease subtypes with potential differences in disease kinetics. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Dutch Gastrointestinal Stromal Tumor (GIST) Registry Data Comparing Sunitinib with Imatinib Dose Escalation in Second-Line Advanced Non-KIT Exon 9 Mutated GIST Patients.

The prognosis of patients with advanced gastrointestinal stromal tumor (GIST) has improved greatly after theintroduction of imatinib. However, primary or secondary resistance to imatinib occurs in the majority of patients. Sunitinib is the standard second line treatment in exon-9 mutated GIST. We compared the clinical outcomes of sunitinib with imatinib dose escalation in patients with progressive advanced non-KIT exon 9 mutated GIST after failure of first line imatinib. A retrospective study was performed, retrieving data from a real-life database (Dutch GIST Registry) including patients with GIST treated with sunitinib or imatinib dose escalation after failure on first line imatinib 400 mg daily. Primary outcome measures were progression free survival (PFS) and overall survival (OS). In total, 110 patients were included, 72 (65.5%) patients were treated with sunitinib (group A) and 38 (34.5%) received an imatinib dose escalation (group B). Important prognostic features at baseline, such as tumor size, stage at diagnosis, mitotic count and localization were equally distributed in both groups. No significant difference (p = 0.88) between median PFS in group A [8.7 months (95% CI 5.6-11.3)] and group B [5.6 months, (95% CI 2.6-8.7)] was observed. Moreover, the OS was similar between group A and group B; 63.2 months and 63.4 months, respectively. This study represents a proper sample size cohort containing detailed data on mutational status of patients with advanced GIST. We illustrated that imatinib dose escalation could serve as a good alternative for sunitinib as second-line treatment in patients with a non-KIT exon 9 mutation.

The Overall Survival and Progression-Free Survival in Patients with Advanced Adrenocortical Cancer Is Increased after the Multidisciplinary Team Evaluation.

Simple SummaryAdrenocortical carcinoma (ACC) is a rare and malignant disease with a poor prognosis in advanced disease. The complexity of ACC management requires a multidisciplinary approach, an emerging model of treatment, suitable for oncological diseases. Our study aims to determine the role of multidisciplinary team evaluation in affecting the overall survival and progression-free survival in ACC patients. We perform a retrospective analysis of ACC patients treated in Padova, with particular reference to their discussion in the multidisciplinary group of adrenal disease, definitively established in 2013 and defined as a collegial meeting between physicians involved in adrenal diseases. We describe a positive impact on survival rates in ACC patients after the multidisciplinary meeting.We aimed to evaluate the role of adrenal multidisciplinary team evaluation (MTE) in affecting the overall survival (OS) and progression-free survival (PFS) in patients with adrenocortical carcinoma (ACC). We included in a retrospective monocentric study 47 patients with ACC. We divided our cohort into group 1 (without adrenal-MTE discussion, ACC diagnosis from 2004 to 2012, n = 14) and group 2 (diagnosis and beginning of treatments after 2013, all discussed in the adrenal MTE, n = 33). OS was defined by the survival between the first and the last visit, while PFS as the time from the first visit to the progression of the disease. Kaplan–Meier curves were used to compare OS and PFS between Group 1 and Group 2. Group 1stages III–IV (n = 10) presented a shorter median OS than Group 2stages III–IV (25 patients, 4 vs. 31 months, p = 0.023). Likewise, the median PFS was lower in Group 1 as compared to Group 2 (2.9 vs. 17.2 months, p < 0.001). The gain in PFS (6 months) was also confirmed in stage III-IV patients (2.9 vs. 8.7 months, respectively, for Group 1 and Group 2, p = 0.02). Group 1 presented a median PFS of 4 months, while the median PFS of Group 2 was 14.7 months (p = 0.128). In conclusion, we found a significant gain in terms of survival in patients after the MTE discussion in 2013. Therefore, ACC patients should be referred to a tertiary center, ideally from the time of diagnosis, to promptly apply all available treatments, according to the single patient’s clinical history and based on multidisciplinary management.

Drug-Eluting Bead Bronchial Arterial Chemoembolization With and Without Microwave Ablation for the Treatment of Advanced and Standard Treatment-Refractory/Ineligible Non-Small Cell Lung Cancer: A Comparative Study.

PurposeTo compare the outcomes of drug-eluting bead bronchial arterial chemoembolization (DEB-BACE) with and without microwave ablation (MWA) for the treatment of advanced and standard treatment-refractory/ineligible non-small cell lung cancer (ASTRI-NSCLC).Materials and MethodsA total of 77 ASTRI-NSCLC patients who received DEB-BACE combined with MWA (group A; n = 28) or DEB-BACE alone (group B; n = 49) were included. Clinical outcomes were compared between groups A and B. Kaplan–Meier methods were used to compare the median progression-free survival (PFS) or overall survival (OS) between the two groups. Univariate and multivariate Cox proportional hazards analyses were used to investigate the predictors of OS for ASTRI-NSCLC treated with DEB-BACE.ResultsNo severe adverse event was found in both groups. Pneumothorax was the predominant MWA-related complication in group A, with an incidence rate of 32.1% (9/28). Meanwhile, no significant difference was found in DEB-BACE-related complications between groups A and B. The overall disease control rate (DCR) was 61.0% (47/77), with a significantly higher DCR in group A (85.7% vs. 46.9%, P = 0.002). The median PFS in groups A and B was 7.0 and 4.0 months, respectively, with a significant difference (P = 0.037). The median OS in groups A and B was both 8.0 months, with no significant difference (P = 0.318). The 6-month PFS and OS rates in groups A and B were 75.0% and 78.6%, 22.4% and 59.2%, respectively, while the 12-month PFS and OS rates in groups A and B were 17.9% and 28.6%, 14.3% and 22.4%, respectively. Of these, a significantly higher 6-month PFS rate was found in group A (75.0% vs. 22.4%; P < 0.001). The cycles of DEB-BACE/bronchial artery infusion chemotherapy [hazard ratio (HR): 0.363; 95% confidence interval (CI): 0.202–0.655; P = 0.001] and postoperative immunotherapy (HR: 0.219; 95% CI: 0.085–0.561; P = 0.002) were identified as the predictors of OS in ASTRI-NSCLC treated with DEB-BACE.ConclusionMWA sequentially combined with DEB-BACE was superior to DEB-BACE alone in the local control of ASTRI-NSCLC. Although the combination therapy reveals a trend of prolonging the OS, long-term prognosis warrants an investigation with a longer follow-up.

Sequential Docetaxel in ≥7 Cycles Followed by Cabazitaxel Improves Oncological Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer

Background. Docetaxel (DOC) was the first regimen that increased the survival and became the standard-of-care in patients with metastatic castration-resistant prostate cancer (mCRPC). However, it is unclear whether switching to second-line chemotherapy or optimal sequencing of cabazitaxel (CBZ) ensures better clinical outcomes. We aimed to evaluate the efficacy of sequential therapy with DOC and CBZ and the effect of the number of prior DOC cycles on oncological outcomes in patients with mCRPC. Methods. We retrospectively included 46 mCRPC patients who received DOC followed by CBZ at quaternary hospitals in Japan between February 2015 and March 2019. Participants received intravenous DOC (40–75 mg/m2) every 3–4 weeks; CBZ (15–25 mg/m2) was administered every 3–4 weeks. Androgen-deprivation therapy and prednisolone 5 mg (twice daily) were administered throughout both regimens. The primary endpoints were overall (OS) and progression-free survival (PFS). The secondary endpoints were the rates of ≥30% and ≥50% reduction in prostate-specific antigen (PSA) levels at chemotherapy initiation. Results. Participants were divided into two groups according to DOC cycles (Groups A and B: ≤6 and ≥7 DOC cycles, respectively). The rates of ≥30% and ≥50% reduction in PSA levels were higher in Group B than in Group A, but there were no significant differences in both groups. Median OS in Groups A and B was 12.7 and 71.0 months, respectively P &lt; 0.001 ; median PFS in Groups A and B was 3 and 12 months, respectively P &lt; 0.001 . Conclusions. Administration of ≥7 cycles of DOC followed by CBZ may improve oncological outcomes in patients with mCRPC.

Does the Waiting Period for Genetic Tests Affect the Prognosis in Chemotherapy-Treated de novo Metastatic Non-Small Cell Lung Cancer Patients without a Driver Mutation?

Introduction: The length of the necessary waiting period to test driver mutations may generate anxiety in patients and clinicians. For this reason, an investigation was conducted to determine whether the duration between diagnosis and the start of first-line chemotherapy (DDC) in non-small cell lung cancer (NSCLC) patients without driver mutations has an impact on prognosis. Methods: The study included 303 de novo metastatic NSCLC patients without a driver mutation and patients were divided into 2 groups according to DDC: ≤30 days (group A) or >30 days (group B). The determinant factors for progression-free survival (PFS) and overall survival (OS) were examined by Cox regression analysis. Results: The mean DDC was calculated as 38.2 ± 54.5 days. The number of patients in group A and B were 183 and 120, respectively. The median PFS in groups A and B was 5.0 and 6.0 months (p = 0.268) and the median OS was 10.0 and 11 months, respectively (p = 0.341). Univariate and multivariate analyses revealed that DDC was not a factor associated with PFS and OS. Conclusion: Our results show that a higher DDC was not associated with a worse prognosis in metastatic NSCLC patients without driver mutations. In this context, it is safer for patients and their physicians to wait for test results before starting chemotherapy.

Abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with hormone receptor-positive, HER2-positive advanced breast cancer (monarcHER): a randomised, open-label, phase 2 trial

Patients with HER2-positive breast cancer who have received two or more previous therapies for advanced disease have few effective treatment options. The monarcHER trial aimed to compare the efficacy of abemaciclib plus trastuzumab with or without fulvestrant with standard-of-care chemotherapy of physician's choice plus trastuzumab in women with advanced breast cancer. This phase 2, three-group, open-label trial was done across 75 hospitals, clinics, and medical centres in 14 countries. Eligible patients were women aged 18 years or older, who had hormone receptor-positive, HER2-positive advanced breast cancer with unresectable, locally advanced, recurrent or metastatic disease, Eastern Cooperative Oncology Group performance status of 0 or 1, and who had previously received at least two HER2-targeted therapies for advanced disease. Patients were randomly assigned 1:1:1 to the abemaciclib, trastuzumab, and fulvestrant (group A), abemaciclib and trastuzumab (group B), or standard-of-care chemotherapy and trastuzumab (group C). Oral abemaciclib 150 mg 12 hourly was administered on days 1-21 of a 21-day cycle, intravenous trastuzumab 8 mg/kg on cycle 1 day 1, followed by 6 mg/kg on day 1 of each subsequent 21-day cycle, and intramuscular fulvestrant 500 mg on days 1, 15, and 29 and once every 4 weeks thereafter. Standard-of-care chemotherapy was administered as specified by the product label. Randomisation was by a computer-generated random sequence by means of an interactive web-response system and stratified by number of previous systemic therapies for advanced breast cancer and measurable versus non-measurable disease. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population, first testing group A versus group C and, if this result was significant, then group B versus group C. Safety was assessed in all patients who had received at least one dose of study treatment. This trial is registered at ClinicalTrials.gov (NCT02675231) and is ongoing for long-term survival follow-up. Between May 31, 2016, and Feb 28, 2018, 325 patients were screened, of whom 237 eligible patients were enrolled and randomly assigned to groups A (n=79), B (n=79), and C (n=79). Median follow-up was 19·0 months (IQR 14·7-25·1). The study met its primary endpoint, showing a significant difference at the prespecified two-sided α of 0·2 in median progression-free survival between group A (8·3 months, 95% CI 5·9-12·6) and group C (5·7 months, 5·4-7·0; HR 0·67 [95% CI 0·45-1·00]; p=0·051). No difference was observed between median progression-free survival in group B (5·7 months, 95% CI 4·2-7·2) and group C (HR 0·94 [0·64-1·38]; p=0·77). The most common grade 3-4 treatment-emergent adverse event in groups A, B, and C was neutropenia (21 [27%] of 78 patients, 17 [22%] of 77, and 19 [26%] of 72). The most common serious adverse events were: in group A, pyrexia (three [4%]), diarrhoea (two [3%]), urinary tract infection (two [3%]), and acute kidney injury (two [3%]); in group B, diarrhoea (two [3%]) and pneumonitis (two [3%]); and in group C, neutropenia (four [6%]) and pleural effusion (two [3%]). Two deaths were attributed to treatment: one due to pulmonary fibrosis in group B and one due to febrile neutropenia in group C. The combination of abemaciclib, fulvestrant, and trastuzumab significantly improved progression-free survival versus standard-of-care chemotherapy plus trastuzumab while showing a tolerable safety profile. Our results suggest that a chemotherapy-free regimen might potentially be an alternative treatment option for patients with hormone receptor-positive, HER2-positive advanced breast cancer. Eli Lilly and Company.

Systemic Therapy Plus Thermal Ablation Versus Systemic Therapy Alone for Oligometastatic Liver Metastases from Non-small Cell Lung Cancer.

This study assessed and compared the efficacy and long-term outcomes of systemic therapy plus image-guidedthermal ablation versus systemic therapy alone for oligometastatic liver metastases (LMs) from non-small cell lung cancer (NSCLC). This retrospective study was approved by the institutional review board. Written informed consent was waived due to the retrospective design. From November 2012 to December 2017, 61 patients (mean age 59.0years; 35 males) with oligometastatic LMs from NSCLC (≤ 5 metastatic lesions) who received systemic therapy with (n = 21, group A) or without (n = 40, group B) thermal ablation were analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier curves. The demographic and clinical characteristics were not significantly different between the groups (all P ≥ .05). In total, 28 LMs were entirely ablated, rendering a technical success rate of 100%, without major complications. The overall 6-month response rate was significantly higher in group A than ingroup B [57.1% (12/21) vs. 26.3% (10/38); P = .026]. The median PFS in group A was significantly longer than in group B [11.0 (95% CI 7.9-16.2) months vs. 5.2 (95% CI 3.7-7.9) months; P = .001]. However, the median OS was not significantly different [27.7 (95% CI 20.6-44.4) months vs. 17.7 (95% CI 14.5-27.5) months; P = .152]. Systemic therapy plus thermal ablation may prolong PFS but not OS in oligometastatic LMs from NSCLC.

Mutation Variants and Co-Mutations as Genomic Modifiers of Response to Afatinib in HER2-Mutant Lung Adenocarcinoma.

Human epidermal growth factor receptor 2 (HER2)-mutant lung cancer remains an orphan of specific targeted therapy. The variable responses to anti-HER2 therapies in these patients prompt us to examine impact of HER2 variants and co-mutations on responses to anti-HER2 treatments in lung cancer. Patients with stage IV/recurrent HER2-mutant lung cancers identified through next-generation sequencings were recruited from seven hospitals. The study comprised a cohort A to establish the patterns of HER2 variants and co-mutations in lung cancer and a cohort B to assess associations between HER2 variants, co-mutations, and clinical outcomes. The study included 118 patients (cohort A, n = 86; cohort B, n = 32). Thirty-one HER2 variants and 35 co-mutations were detected. Predominant variants were A775_G776insYVMA (49/118, 42%), G778_P780dup (11/118, 9%), and G776delinsVC (9/118, 8%). TP53 was the most common co-mutation (61/118, 52%). In cohort B, objective response rates with afatinib were 0% (0/14, 95% confidence interval [CI], 0%-26.8%), 40% (4/10, 14.7%-72.6%), and 13% (1/8, 0.7%-53.3%) in group 1 (A775_G776insYVMA, n = 14), group 2 (G778_P780dup, G776delinsVC, n = 10), and group 3 (missense mutation, n = 8), respectively (p = .018). Median progression-free survival in group 1 (1.2 months; 95% CI, 0-2.4) was shorter than those in group 2 (7.6 months, 4.9-10.4; hazard ratio [HR], 0.009; 95% CI, 0.001-0.079; p < .001) and group 3 (3.6 months, 2.6-4.5; HR, 0.184; 95% CI, 0.062-0.552; p = .003). TP53 co-mutations (6.317; 95% CI, 2.180-18.302; p = .001) and PI3K/AKT/mTOR pathway activations (19.422; 95% CI, 4.098-92.039; p < .001) conferred additional resistance to afatinib. G778_P780dup and G776delinsVC derived the greatest benefits from afatinib among HER2 variants. Co-mutation patterns were additional response modifiers. Refining patient population based on patterns of HER2 variants and co-mutations may help improve the efficacy of anti-HER2 treatment in lung cancer. Human epidermal growth factor receptor 2 (HER2)-mutant lung cancers are a group of heterogenous diseases with up to 31 different variants and 35 concomitant genomic aberrations. Different HER2 variants exhibit divergent sensitivities to anti-HER2 treatments. Certain variants, G778_P780dup and G776delinsVC, derive sustained clinical benefits from afatinib, whereas the predominant variant, A775_G776insYVMA, is resistant to most anti-HER2 treatments. TP53 is the most common co-mutation in HER2-mutant lung cancers. Co-mutations in TP53 and the PI3K/AKT/mTOR pathway confer additional resistance to anti-HER2 treatments in lung cancer. The present data suggest that different HER2 mutations in lung cancer, like its sibling epidermal growth factor receptor, should be analyzed independently in future studies.

EP1.04-39 Is Body Mass Index a Prognostic Factor in Patients with Lung Cancer Treated with Immunotherapy?

Non-small cell lung cancer (NSCLC) is a prevalent disease with high mortality and poor response to traditional cytotoxic therapy. Immune checkpoint inhibitors (ICI) approvals were the landmark in the last years for the treatment of lung cancer. With these treatments, many patients with advanced disease are starting to see durable responses and longer survival rates. Several factors like obesity has been previously investigated for its role in cancer and promoting tumor growth, at least partially by inducing a chronic inflammatory state, but it’s unclear how it links to immunotherapy, where inflammation has been linked to treatment response,” High Body mass index (BMI) might have a positive impact in the outcomes of patients who are taking PD-1 or PD-L1 inhibitors, according to a recent study. In this study, we aim to determine if the body mass index (BMI) is a prognostic factor in patients treated with immunotherapy We retrospectively evaluated the outcomes of 30 patients with NSCLC confirmed histology, aged 18 years or older, treated with anti PD-1/PD-L1 from 2016 to 2018. BMI was stratified unto 2 groups: 1) normal and under-weighted (BMI < 25 kg/ m2) and 2) over-weighted and obese (BMI ≥ 25 kg/ m2). Simple descriptive statistics were created for all covariates. After statistical analyses with Kruskal-Wallis equality-of-populations rank test were related to progression free survival (PFS). A total of 30 lung cancer patients were enrolled in this study, divided by gender as 10 female-patients (33,33%) and 20 masculine-patients (66,67%) The median age was 63 years (youngest 41-year-old and oldest 81 years old). According to histology 20 patients have adenocarcinoma (66,67 %) and 10 patients have squamous tumors (33,33%). Analyzing the mutational status, the majority was EGFR Wild type (WT). The majority of patients involved (43,33 %; 13 patients) were given immunotherapy in the third-line setting or beyond. More than half of patients had over-weighted and obese BMI (group 2 – 56,67% (n=17)). The median follow-up was 86 days (1 quartile 35 days and 3rd quartile 291 days (minimum 5 days, maximum 971 days). The median PFS in group 1 was 98 days (1 quartile 56 days and 3rd quartile 407 days (minimum 28 days, maximum 495 days) and in over-weighted and obese was 74 days (1quartil 26 days and 3rd quartile 127 days (minimum 5 days, maximum 971 days). There were no statistical differences in PFS (p= 0,249) between higher or lower BMI groups (group1 vs. group 2). In this single institution cohort, BMI hadn’t a significant effect on outcomes of patients with lung cancer receiving anti PD-1/PD-L1 agents. As a critic to this evaluation we have that is for now a small group of patients and we think it is important to maintain studies in this field as the number of patients under this therapy increases.

Safety and Efficacy of Transcatheter Arterial Chemoembolization Plus Radiotherapy Combined with Sorafenib in Hepatocellular Carcinoma with Macrovascular Invasion

The safety and efficacy of transcatheter arterial chemoembolization (TACE) plus intensity-modulated radiotherapy (IMRT) combined with sorafenib in hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) remains controversial. We compared the survival and safety of TACE plus IMRT with TACE plus RT and sorafenib in patients with HCC with MVI. The medical records of 63 consecutive patients with advanced-stage HCC showing MVI, who underwent IMRT plus TACE combined with (28participants; Group A) or without (35 participants; Group B) sorafenib from October 2015 to October 2018, were retrospectively reviewed to assess the overall survival (OS), progression-free survival (PFS), tumor response, and treatment-associated toxicity. The propensity score matching (PSM) method was used to comprehensively analyze the effects between Group A and Group B. The median follow-up time was 14.1 months. The overall response rate (ORR) was achieved in 46.4% of patients with complete response (CR) in 10.7% of patients at 3 months after IMRT in Group A, while the ORR and CR rate were 45.7% and 0% in Group B. The median PFS in Group A (13.6 months, 95% CI =11.2-16.1) was longer than that in Group B (9.2 months, 95%CI =7.0-11.3) (P=0.044), and it was still significant after PSM (P=0.033). However, the median OS was similar in the two groups (19.0 vs 15.2 months, P=0.094 before PSM; P=0.204 after PSM). The grade 3 hematologic toxicity was present in 10 patients (15.9%), including 4 patients in Group A and 6 patients in Group B (14.3% vs 17.1%, P=1.000). Seven of 63 patients, including 3 patients in Group A (10.7%) and 4 patients in Group B (11.4%) (P=1.000), developed grade 3 hepatic toxicity. Incidences of skin reaction, hand-foot syndrome and diarrhea, which were all 1-2 grade adverse events, were significantly higher (P=0.027, 0.014, and 0.001, respectively) in Group A (92.9%, 17.9%, and 28.6%, respectively) than that in Group B (68.6%, 0%, and 0%, respectively). No patient experienced grade 4 or 5 toxicity, and radiation-induced liver disease was also not observed. TACE plus IMRT combined with sorafenib showed a good safety profile and clinical benefit in HCC patients with MVI.

Antibiotic use is a negative predictor of the efficacy and toxicity of epidermal growth factor receptor-targeted therapy in advanced non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is closely associated with inflammation and chronic infection. Antibiotics are frequently prescribed for NSCLC patients in combination with epidermal growth factor receptor (EGFR)-targeted treatment in the presence of infection. The association between antibiotic use and the efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) has not previously been thoroughly investigated. Therefore, the present study investigated whether antibiotics could affect the efficacy and toxicity of EGFR-TKI treatment, with the aim of restricting the use of antibiotics in combination with targeted therapy in patients with advanced NSCLC in the near future. All patients received treatment with EGFR-TKIs until disease progression, unacceptable toxicity or other factors, including death, pregnancy or unwillingness to further receive targeted therapy, were observed. Patients were retrospectively divided into two groups: Group A, which was treated with EGFR-TKIs and antibiotics; and Group B, which was treated with EGFR-TKIs alone. Patients having used antibiotics 6 months prior to EGFR-TKI therapy were also included in the study. Antibiotic use negatively affected the median progression-free survival (PFS) following EGFR-TKI treatment in NSCLC compared with that in patients not treated with antibiotics; median PFS in Group A was 6.6 months, whereas median PFS in Group B was 10.1 months. Antibiotics also increased the toxicity of targeted therapy for advanced NSCLC. There were significant statistical differences between the two groups in the occurrence of the adverse events of diarrhea and dyspnea. In conclusion, antibiotics decreased the efficacy of first-line targeted therapy in advanced NSCLC and increased incidences of diarrhea and dyspnea. Large randomized studies are needed to identify the impact of antibiotic use on EGFR-TKI treatment for NSCLC.

Survival benefit of first-generation epidermal growth factor receptor-tyrosine kinase inhibitors in female with advanced lung cancer.

This study aimed to estimate therapeutic effects of first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in real-world practice, by analyzing survival outcomes in an unselected, Korean female population with advanced lung cancer based on the National Health Insurance Service database. We identified women with newly diagnosed advanced lung cancer from January 2004 to December 2013. For progression-free survival (PFS) and overall survival (OS) analyses, patients were defined into the following subgroups: group A, treated with first-generation EGFR-TKI ⩾6 months; group B, treated with EGFR-TKIs <6 months but at least >1 month; and group C, treated with cytotoxic chemotherapy as follows: monotherapy or combination therapy with gemcitabine or pemetrexed; or monotherapy with docetaxel, paclitaxel, or vinorelbine. Among 11,045 enrolled patients, 6170 (55.8%) were treated with first-generation EGFR-TKIs for at least 1 month. The median OS for patients treated with EGFR-TKIs was significantly longer than that of EGFR-TKI-naive patients (19.1 months [95% confidence interval (CI) 18.5-19.7] vs 9.5 months [95% CI 9.1-9.8], P<0.001). In subgroup analysis, group A had a significantly longer median OS compared with group B (30.3 months [95% CI 29.5-31.2] vs 12.3 months [95% CI 11.9-12.7], P<0.001). The median PFS of group A was significantly longer than that of group B (15.8 vs 3.7 months, P<0.001). Our analysis demonstrates that EGFR-TKIs confer significant PFS and OS benefits in the real-world practice for Korean female with advanced lung cancer.

Cohort Study on Prognosis of Patients with Metastatic Colorectal Cancer Treated with Integrated Chinese and Western Medicine.

To investigate the efficacy of integrated Chinese and Western medicine (IM) in the treatment of metastatic colorectal cancer (mCRC) in a cohort study. The survival outcome of patients receiving IM was compared with that of patients receiving Western medicine alone. The study design was adopted with "continuous administration of Chinese medicine for ⩾ 3 months" as the exposure factor. Patients who met this exposure factor were assigned to the IM cohort (Group A, 110 patients). Patients who did not meet this exposure factor were assigned to the Western medicine cohort (Group B, 225 patients). The overall survival (OS), progression-free survival (PFS), and 1st year, 2nd year, and 3rd year survival in the two cohorts were compared. The median OS in Group A and B were 18 months [95% confidence interval (CI) 15-21] and 16 months (95% CI 14-18), respectively, and the median PFS in Group A and B were 6 months (95% CI 4-7) and 5 months (95% CI 4-6), respectively. No statistically significant differences were observed between the groups (P=0.186, P=0.223). Group A demonstrated significantly longer OS and PFS than Group B in the following subgroups: female patients, patients with lesions in the right half of the colon, and those who received first-line treatment (P<0.05). In the subgroup of elderly patients (age>65 years), the OS in Group A was longer than that in Group B (P<0.05). IM could prolong the survival of patients with mCRC. (Registry No. ChiCTR-IOR-17010497).

Ibrutinib-Based Therapy in the Treatment of Relapsed and Refractory Chronic Lymphocytic Leukemia

Introduction. The development of Bruton's tyrosine kinase inhibitors and their introduction into clinical practice represent a major advance in the treatment of chronic lymphocytic leukemia (CLL). Several studies in CLL have determined the achievement of minimal residual disease (MRD) negativity as an independent favorable prognostic factor, associated with superior progression-free survival (PFS) and overall survival. MRD status is the single best posttreatment predictor of long-term outcomes after treatment, regardless of the treatment protocol or the presence of other pre-existing prognostic indicators.Aim.To estimate of response rate, PFS and MRD after ibrutinib-based therapy in the treatment patients with relapsed/refractory CLL.Methods.21 pts with relapsed/refractory CLL were included in the analysis. Stratification of patients into groups based on therapy. Group 1 (n = 14): 2nd and subsequent lines of rituximab-based chemotherapy (RB - 10, FCR - 4) and Group 2 (n = 12): ibrutinib-based therapy (420 mg daily oral Ibrutinib ± Chemoimmunotherapy). We have used NCI-IWCLL revised guidelines for treatment initiation and assessment of response. MRD was detected by multicolor flow cytometry of bone marrow in patients achieved a complete or partial remission: Group 1 - 7 pts, Group 2 - 5 pts.Results. The median age was 60.5 years (45-83) in Group 1 and 62.5 years (49-82) in Group 2 and median previous lines of therapy was 1 (1-4) and 2 (1-4), respectively. Patients with unfavorable chromosomal abnormalities were detected in each group: Group 1 - 2 pts (combination del(11q) with del(13q)); Group 2 - 1 pts (del(17p)).Overall response rate (ORR) in Group 1 was 71.4% (complete remission (CR) - 1 pt, partial remission (PR) - 9 pts, stable disease (SD) - 3 pts, progression disease - 1 pt). Group 2: ORR 91.7% (CR - 3 pts, PR - 8 pts; SD - 1 pt). Statistically significant differences in the frequency of ORR between groups were not detected (p>0.05).MRD-negative remission rate was 40% (2/5, CR - 1 pt) in Group 2 compared to 14.3% (1/7 pts, CR) in Group 1 (p>0.05). Statistically significant differences in PFS were detected between Group 1 vs. Group 2 (p=0.0006). Median PFS in Group 2 has not been reached. Median PFS in Group 1 was 16.9 month.Conclusion. Ibrutinib is highly effective at controlling disease, but best responses are typically partial remission, and patients must remain on treatment to maintain disease control. Evaluation of response and MRD after ibrutinib-containing therapy in the treatment of patients with relapsed/refractory chronic lymphocytic leukemia require further research. DisclosuresShuvaev:Pfizer: Honoraria; BMS: Honoraria; Novartis pharma: Honoraria.

Pre-Operative Perfusion Skewness and Kurtosis Are Potential Predictors of Progression-Free Survival after Partial Resection of Newly Diagnosed Glioblastoma.

ObjectiveTo determine whether pre-operative perfusion skewness and kurtosis derived from normalized cerebral blood volume (nCBV) histograms are associated with progression-free survival (PFS) of patients after partial resection of newly diagnosed glioblastoma.Materials and MethodsA total of 135 glioblastoma patients who had undergone partial resection of tumor (resection of < 50% of pre-operative tumor volume or surgical biopsy) confirmed with immediate postsurgical MRI and examined with both conventional MRI and dynamic susceptibility contrast (DSC) perfusion MRI before the surgery were retrospectively reviewed in this study. They had been followed up post-surgical chemoradiotherapy for tumor progression. Using histogram analyses of nCBV derived from pre-operative DSC perfusion MRI, patients were sub-classified into the following four groups: positive skewness and leptokurtosis (group 1); positive skewness and platykurtosis (group 2); negative skewness and leptokurtosis (group 3); negative skewness and platykurtosis (group 4). Kaplan-Meier analysis and multivariable Cox proportional hazards regression analysis were performed to determine whether clinical and imaging covariates were associated with PFS or overall survival (OS) of these patients.ResultsAccording to the Kaplan-Meier method, median PFS of group 1, 2, 3, and 4 was 62, 51, 39, and 41 weeks, respectively, with median OS of 82, 77, 77, and 72 weeks, respectively. In multivariable analyses with Cox proportional hazards regression, pre-operative skewness/kurtosis pattern (hazard ratio: 2.98 to 4.64; p < 0.001), Karnofsky performance scale score (hazard ratio: 1.04; p = 0.003), and post-operative tumor volume (hazard ratio: 1.04; p = 0.02) were independently associated with PFS but not with OS.ConclusionHigher skewness and kurtosis of nCBV histogram before surgery were associated with longer PFS in patients with newly diagnosed glioblastoma after partial tumor resection.