Chemotherapy and Radiation Versus Chemotherapy Alone for Elderly Patients With N3 Stage IIIB NSCLC

BackgroundStandard treatment for stage III non–small-cell lung cancer (NSCLC) is concurrent chemotherapy and radiation (chemo-RT). However, N3 stage IIIB disease portends a worse prognosis and the tolerability of chemo-RT in patients ≥70 years old is a concern. In this analysis, we evaluate the survival of patients with N3 stage IIIB NSCLC who were treated with chemo-RT or chemotherapy alone with a focus on elderly patients.Patients and MethodsWe retrospectively analyzed patients diagnosed with N3 stage IIIB NSCLC between 2010 and 2013 using the National Cancer Database. We compared overall survival (OS) between patients who underwent chemo-RT versus chemotherapy alone. The Kaplan–Meier method was used for median OS with log rank tests. Multivariable Cox models were used for multivariable and subgroup analyses.ResultsWe included 9769 patients in our analysis, 7770 of whom received chemo-RT and 1999 who received chemotherapy alone. The median OS for patients who received chemo-RT was 16.4 months versus 12.7 months with chemotherapy alone (P < .0001). The median OS for patients ≥70 years old who received chemo-RT was 15.0 months versus 12.4 months with chemotherapy alone (P < .0001). In multivariable analyses, the benefit of chemo-RT was similar regardless of age. Subgroup analyses in patients ≥70 years indicated a benefit of chemo-RT (hazard ratio, <1.0) across all patient and disease strata.ConclusionSurvival was improved in elderly patients who received chemo-RT versus chemotherapy alone for N3 stage IIIB NSCLC. Our findings suggest that age and comorbidities should not preclude clinicians from recommending chemo-RT to these patients.     

Randomized Phase II Trial of Abiraterone Alone or With Dasatinib in Men With Metastatic Castration-resistant Prostate Cancer (mCRPC)

BackgroundSignaling via the Src pathway is thought to be a mediator of resistance to androgen targeted therapy in prostate cancer. We studied whether adding the Src inhibitor dasatinib to abiraterone would delay progression.Patients and MethodsEligible patients had metastatic castration-resistant prostate cancer (mCRPC), without prior chemotherapy. Abiraterone was prescribed at 1000 mg daily with prednisone 5 mg twice daily in both arms, and dasatinib 100 mg daily was added for Arm B. The primary endpoint was progression-free survival (PFS). The interim analysis was planned after 48 subjects, but the study was terminated early. PFS was evaluated using a 1-sided log rank test. The Fisher exact test was used for other categorical data analyses. Circulating tumor cells (CTCs) were identified with the Epic platform.ResultsWith 26 men randomized and a median follow up of 41.8 months, the median PFS was 15.7 months (95% confidence interval, 8.2-49.0+ months) for Arm B and 9.0 months (95% confidence interval, 4.4-30.7 months) for Arm A (P = .15). Response Evaluation Criteria in Solid Tumors responses were seen in 5 (36%) of 14 patients, including 2 complete responses (CRs) on Arm B, and 2 (17%) of 12 responses without CR on Arm A (P = .39). Grade ≥ 3 toxicities more common in Arm B included hypertension, pleural effusion/dyspnea, and gastrointestinal effects. CTCs were detected at baseline in 10 of 19 evaluable patients (median, 2.7/mL blood [range 0.41-59.7]). At week 4, CTCs increased in 1 (10%) of 10 patients on Arm A and 4 (44%) of 9 patients on Arm B.ConclusionDasatinib did not significantly prolong PFS in combination with abiraterone, although power was limited owing to the incomplete study cohort. Treatment with the combination was associated with robust objective responses, including Response Evaluation Criteria in Solid Tumors CRs.     

Association of Hyponatremia With Survival in Patients With Castration-resistant Prostate Cancer: A Clinical Commentary

IntroductionThe aim of this study was to evaluate the prognostic value of hyponatremia in patients with castration-resistant prostate cancer (CRPC) undergoing docetaxel chemotherapy.Patients and MethodsWe retrospectively assessed 186 patients who received docetaxel chemotherapy in addition to androgen deprivation for CRPC between 2005 and 2015. We stratified the patients according to their pre-chemotherapy serum sodium level. Hyponatremia was defined as sodium < 135 mmol/L. A Cox proportional regression model was used to estimate overall survival (OS).ResultsThe median sodium level was 139 mmol/L (interquartile range, 137-141 mmol/L). Hyponatremia was detected in 13 (6.9%) patients. One-half of the patients died during the studied period. The presence of hyponatremia was associated with a decreased probability of OS (hazard ratio, 2.5; 95% confidence interval, 1.0-6.3; P = .04) in univariate analysis. These findings could not be confirmed in the multivariable OS model (P = .21).ConclusionWe observed an association between hyponatremia and worse survival outcomes in our patients with CRPC undergoing docetaxel chemotherapy. However, further well-designed studies with full workup of hyponatremia are needed to validate these findings and to identify the underlying causes for this association in patients with CRPC.     

Association of mTOR Pathway Markers and Clinical Outcomes in Patients with Intermediate-/High-risk Prostate Cancer: Long-Term Analysis

IntroductionThe mammalian target of rapamycin (mTOR) pathway is up-regulated in prostate cancer (PCa). We evaluated the tumor tissue expression of downstream mTOR targets in patients with intermediate- and high-risk (IR/HR) PCa and their ability to predict outcome after radical prostatectomy (RP).Patients and MethodsImmunohistochemical (IHC) analysis using antibodies against PTEN, mTOR, p-mTOR, pAKT, pS6, and Ki-67 was performed on a tissue microarray constructed from formalin-fixed paraffin-embedded RP specimens. The marker expression was analyzed to determine their predictability for biochemical recurrence (BCR).ResultsTumor tissue from 217 patients (86 IR/131 HR) was analyzed. The most frequent markers were p-mTOR, which was expressed in most cases (85%), whereas PTEN and pS6 were detected in 53% and 40% of the cases, respectively. Overexpression of PTEN (P = .02) and pS6 (P < .001) was associated with HR features. With a median follow up of 13.5 years, 39% (77/196) of patients developed BCR after RP, more frequently (31%) in patients with HR disease (P < .001). Overexpression of pS6 (P = .036), Ki67% (P = .024), and lack of expression of mTOR (P = .021) were associated with BCR. The 5- and 10-year survival rate was 81% and 66%, respectively.ConclusionsProtein expression of downstream mTOR molecules was significantly associated with outcome of patients with IR and HR PCa. Markers of the mTOR pathway could be incorporated in clinical studies evaluating inhibitors of the signaling pathway for treatment selection in men with PCa.     

Disease Characteristics and Completion of Treatment in Patients With Metastatic Castration-Resistant Prostate Cancer Treated With Radium-223 in an International Early Access Program

BackgroundRadium-223 is approved by the US Food and Drug Administration and European Medicines Agency for the treatment of metastatic castration-resistant prostate cancer (mCRPC). There are currently no markers for selecting patients most likely to complete radium-223 treatment.Patients and MethodsIn this phase IIIb, international, single-arm study, patients received radium-223, 55 kBq/kg, every 4 weeks for ≤6 cycles. Primary end points were safety and overall survival. In post hoc analyses patients were grouped according to number of radium-223 injections received (1-4 or 5-6). Associations between baseline covariates and number of injections were investigated.ResultsOf 696 eligible patients, 473 (68%) had received 5 to 6 radium-223 injections and 223 (32%) 1 to 4 injections. Patients with less pain (moderate-severe vs. none-mild, odds ratio [OR], 0.41; P < .0001), lower Eastern Cooperative Oncology Group performance status (≥2 vs. 0-1, OR, 0.51; P = .0074), lower prostate-specific antigen level (>141 μg/L vs. ≤141 μg/L, OR, 0.40; P < .0001), and higher hemoglobin level (<10 g/dL vs. ≥10 g/dL, OR, 0.50; P = .0206) were more likely to receive 5 to 6 than 1 to 4 injections. Median overall survival was not reached and was 6.3 months (95% confidence interval, 5.4-7.4) in patients who had received 5 to 6 and 1 to 4 radium-223 injections, respectively. Adverse events were less common in patients who received 5 to 6 than 1 to 4 injections; anemia was reported in 87 (18%) and 64 (29%) patients, respectively.ConclusionPatients with less advanced mCRPC are more likely to receive 5 to 6 radium-223 injections and to achieve better overall survival. Consideration of baseline and disease characteristics is recommended before initiation of radium-223 treatment.