Eastern Cooperative Oncology Group Poor Performance Status Research Articles

First-Line Gefitinib for Patients With Advanced Non–Small-Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations Without Indication for Chemotherapy

This multicenter phase II study was undertaken to investigate the efficacy and feasibility of gefitinib for patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations without indication for chemotherapy as a result of poor performance status (PS). Chemotherapy-naïve patients with poor PS (patients 20 to 74 years of age with Eastern Cooperative Oncology Group PS 3 to 4, 75 to 79 years of age with PS 2 to 4, and >or= 80 years of age with PS 1 to 4) who had EGFR mutations examined by the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method were enrolled and received gefitinib (250 mg/d) alone. Between February 2006 and May 2007, 30 patients with NSCLC and poor PS, including 22 patients with PS 3 to 4, were enrolled. The overall response rate was 66% (90% CI, 51% to 80%), and the disease control rate was 90%. PS improvement rate was 79% (P < .00005); in particular, 68% of the 22 patients improved from >or= PS 3 at baseline to <or= PS 1. The median progression-free survival, median survival time, and 1-year survival rate were 6.5 months, 17.8 months, and 63%, respectively. No treatment-related deaths were observed. This is the first report indicating that EGFR mutation-positive patients with extremely poor PS benefit from first-line gefitinib. Because there previously has been no standard treatment for these patients with short life expectancy other than best supportive care, examination of EGFR mutations as a biomarker is recommended in this patient population.

Single-Agent Epidermal Growth Factor Receptor Inhibitor Gefitinib for the Treatment of Patients with Advanced Non—Small-Cell Lung Cancer and Poor Performance Status

PurposePatients with advanced non—small-cell lung cancer (NSCLC) have no options for curative therapy; therefore, improving their quality of life (QOL) is also an important treatment goal. Patients with NSCLC and poor performance status (PS) are often excluded from clinical trials. Gefitinib, an epidermal growth factor (EGFR) inhibitor, is a safe oral agent that might benefit these patients. The aim of the study is to evaluate the effect of single-agent EGFR inhibitor gefitinib on the QOL of patients with advanced NSCLC and poor PS. Patients and MethodsNineteen patients with advanced NSCLC and poor PS who were unfit to receive chemotherapy were enrolled on this study of gefitinib 250 mg per day given orally until disease progression. All patients had no previous chemotherapy, an Eastern Cooperative Oncology Group PS of 3, and stage IIIB/IV NSCLC. Response rate, time to disease progression, and overall survival (OS) were calculated. We evaluated the QOL of all eligible patients using the Functional Assessment of Cancer-Lung (FACT-L) questionnaire. FACT-L was used to measure the physical, social/familial, emotional, and functional well-being of the patients as well as lung cancer—specific symptoms and concerns. A Trial Outcome Index (TOI) was derived to assess the physical component of QOL. A mixed-effects linear model was used to examine the effect of potential covariates (age, race, sex, response, and duration of treatment) on the outcome of QOL scores over time. A Cox regression model was used to determine the joint effect of age, race, sex, treatment duration, and baseline TOI score on the OS of the patients. ResultsEleven out of 19 patients were evaluable for this analysis. The median age was 71.8 years (range, 60.9–73.4 years). Six patients had adenocarcinoma, and 5 patients had squamous cell carcinoma, and the median treatment duration was 63.0 days (range, 35–118 days). Grade 3/4 toxicities included fatigue, rash, and diarrhea. One patient had a partial response, 7 patients had stable disease, and 3 patients progressed. The median OS was 5.3 months (range, 2.5–22.1 months), and the median progression-free survival was 3.7 months (range, 2.1–5.8 months). Baseline TOI was weak but significantly associated with OS, with a hazard ratio (HR) of 0.92 (95% CI, 0.85–0.99; P = .03). Duration of treatment was marginally associated with survival, with an HR of 0.98 (95% CI, 0.96–1.0; P = .07). As expected, the total FACT-L score and the TOI were highly correlated (r = 0.96; P < .0001). There were no significant differences in the subscale scores, FACT-General, or the FACT-L between baseline, week 5, and week 8. Notably, an increasing trend of the TOI was observed, ranging from 33.8 at baseline to 42.0 at week 5 to 45.0 at week 8, albeit this trend was not significant. Race and age were significantly associated with the TOI. TOI scores were higher in black patients compared with white patients (P = .03) and increased with age (P = .02). ConclusionSingle-agent EGFR inhibitor gefitinib could be an active and well-tolerated therapy for patients with NSCLC with poor PS, with a trend of the TOI observed for improvement in QOL. Our results suggest that increasing age and black race had higher TOI scores and thus improved QOL status.

Single-Agent Gefitinib in Patients with Untreated Advanced Non–Small-Cell Lung Cancer and Poor Performance Status: A Minnie Pearl Cancer Research Network Phase II Trial

BACKGROUND: Patients with advanced non–small-cell lung cancer (NSCLC) and poor performance status (PS) are often excluded from trials. Gefitinib is a safe oral agent that may benefit these patients. PATIENTS AND METHODS: Seventy-two patients with poor PS and advanced NSCLC were enrolled onto this study of gefitinib 250 mg per day given orally until disease progression, with evaluation at 8 weeks. Eligible patients had no previous chemotherapy, an Eastern Cooperative Oncology Group PS of 2/3, and stage IIIB/IV NSCLC. Quality of life (QOL) and symptom response (SR) scores were calculated using the Functional Assessment of Cancer–Lung questionnaire. Patient characteristics included a median age of 75 years; PS of 2/3; and bronchoalveolar (n = 3), adenocarcinoma (n = 29), squamous cell (n = 21), large-cell (n = 11), and unspecified histology (n = 6). Mean treatment duration was 4 months (range, 3 days to 18 months), and median duration of follow-up was 12 months. Grade 3/4 toxicities included rash and diarrhea. RESULTS: Among 70 patients assessed for response, there were 3 partial responses (4%), 32 patients with stable disease (46%), and 18 with progressive disease (26%). Median progression-free survival (PFS) and overall survival (OS) were 3.7 months and 6.3 months, respectively. Six-month and 1-year PFS and OS rates were 35% and 21% and 50% and 24%, respectively. Eighty-two percent and 48% of patients reported improvements or no change in QOL and SR, respectively. CONCLUSION: Gefitinib demonstrates modest efficacy and is well tolerated as initial therapy in advanced NSCLC for patients with poor PS.

Clinicopathologic and molecular correlations of necrosis in the primary tumor of patients with renal cell carcinoma

The presence of histologic necrosis in the primary tumor of patients with renal cell carcinoma (RCC) has been suggested to be an important predictor of survival. The authors investigated the relation of tumor necrosis to other clinicopathologic factors known to be important prognostic indicators for patients with RCC. The records of 311 patients undergoing treatment for RCC were evaluated for basic clinicopathologic information including TNM classification, nuclear grade, Eastern Cooperative Oncology Group (ECOG) performance status (PS), disease recurrence, and survival. The presence and extent of histologic necrosis of the primary tumors was recorded and correlated with clinicopathologic factors, carbonic anhydrase IX and Ki-67 expression, disease recurrence, and survival. The presence of necrosis in the primary tumor of patients with RCC compared with patients with RCC without necrosis was associated with higher T classification (P < 0.0001), the presence of lymph node disease (P = 0.009), the presence of metastases (P < 0.0001), higher grade (P < 0.0001), greater mean tumor size (P < 0.0001), an ECOG PS score > or = 1 (P = 0.007), higher University of California-Los Angeles Integrated Staging System (UISS) category (P < 0.0001), and higher Ki-67 expression (P < 0.0001). The extent of necrosis in the primary tumor was associated with the presence of lymph node disease (P = 0.009) and the presence of metastases (P < 0.0001), and correlated with higher T classification (sigma = 0.31, P < 0.0001), poorer ECOG PS (sigma = 0.18, P = 0.002), higher grade (sigma = 0.33, P < 0.0001), greater tumor size (sigma = 0.40, P < 0.0001), higher UISS category (sigma = 0.37, P < 0.0001), and higher Ki-67 staining (sigma = 0.32, P < 0.0001). Patients with the presence of necrosis in the primary tumor demonstrated a lower 5-year disease-specific survival compared with patients without necrosis in the primary tumor (36% vs. 75%; P < 0.0001). Multivariate analysis demonstrated that T classification (P < 0.0001), distant metastases (P < 0.0001), and ECOG PS (P < 0.0001) were independent predictors of DSS, whereas the presence of necrosis was not (P = 0.1100). Substratification into localized and metastatic disease demonstrated that the presence of necrosis was an independent predictor of survival in patients with localized (P = 0.025), but not metastatic (P = 0.44), disease. The extent of necrosis was not an independent predictor of survival (P > 0.05). Patients with the presence of necrosis in the primary tumor had a lower 5-year disease recurrence-free rate compared with patients without the presence of necrosis (62% vs. 92%, P < 0.0001). The presence of necrosis in the primary tumor was associated with adverse prognostic factors such as high T classification, presence of lymph node disease and metastases, high grade, large tumor size, and poor ECOG PS. The extent of necrosis was found to be associated with the presence of lymph node disease and metastases and correlated with higher T classification, higher grade, greater tumor size, poorer ECOG PS, and higher UISS category. The presence of this histologic variant was an independent predictor of poor survival in patients with localized, but not metastatic, disease. In addition, Ki-67 expression served as a valuable surrogate marker for the presence of histologic tumor necrosis.

Activity of gefitinib in advanced non-small-cell lung cancer with very poor performance status

Advanced non-small-cell lung cancer (NSCLC) patients with poor performance status (PS) are less likely to respond to chemotherapy, or to have an improvement in survival, but more likely to experience toxicity. We retrospectively evaluated the efficacy and tolerability of gefitinib in patients with advanced NSCLC and very poor PS in Taiwan. Patients with stage IIIB, IV NSCLC with an Eastern Cooperative Oncology Group (ECOG) PS of 3-4 received oral gefitinib 250 mg once daily. Totally, 52 patients were included (25 men, 27 women). Forty-three patients (82.7%) were in a PS of 3. Tumor response rate was 25.0% (13/52). Tumor response rate to gefitinib was highest in chemonaive patients 38.1% (8/21) vs. failed 1 chemotherapy regimen 13.3% (2/15) vs. failed 2 or more chemotherapy regimens 18.8% (3/16), p = 0.015. The median overall survival was 2.5 months (response group 9.1 months, stable disease 3.1 months, and progressive group 0.8 month, p < 0.001). Adverse events, mainly skin reactions and diarrhea, were generally mild (grade 1 or 2) except paronychia and acne. Thus, gefitinib has clinically antitumor activity and good tolerability in Taiwan patients with advanced NSCLC and very poor performance status, with a higher response rate than that seen Europe or in European heritage Americans. Chemonaive patients responded better than patients with prior chemotherapy. Formal clinical trials are warranted to evaluate the role of gefitinib in this situation.

Clinical, pathological, and molecular correlations of necrosis in the primary tumor of patients with renal cell carcinoma

4643 Background: Presence of histologic necrosis in the primary tumor of patients with renal cell carcinoma (RCC) has been demonstrated to be an important predictor of survival. We investigated the relationship of necrosis to other histologic and clinical factors known to be important prognostic indicators for patients with RCC. Methods: The records of 300 patients undergoing treatment for RCC at UCLA were evaluated for basic clinical information including TNM stage, Eastern Cooperative Oncology Group performance status (ECOG-PS), nuclear grade, and survival. Pathologic slides of the primary tumors were reviewed by a single pathologist. Presence and amount of necrosis were correlated with clinical factors, carbonic anhydrase IX (CAIX) expression, and survival. Results: Patents with necrosis presented with higher T stage (p < 0.0001), metastases (p < 0.0001), greater mean tumor size (p < 0.001) and higher grade (p < 0.0001) compared to patients without necrosis. Extent of necrosis in the primary tumor significantly correlated with T stage, nodal status, metastasis, ECOG-PS, grade, tumor size, and UCLA Integrated Staging System (UISS) (p < 0.01). Patients with necrosis demonstrated a significantly lower 5-year disease specific survival compared to patients without necrosis (36% vs. 75%; p < 0.0001). Multivariate analysis demonstrated grade (p = 0.002), T stage (p < 0.0001), and ECOG-PS (p < 0.0001) to be independent predictors of disease specific survival, while necrosis approached significance (p = 0.07). Presence and extent of necrosis were independent predictors of survival in patients with localized (p < 0.05), but not metastatic (p > 0.05) disease. In patients with clear cell histology, necrosis was also an independent predictor of survival for localized (p = 0.04), but not metastatic (p = 0.49) disease. Conclusions: Presence of necrosis in the primary tumor of patients with RCC is associated with large size, high stage, high grade, and poor ECOG-PS, as well as the presence of distant metastases. The presence of this histologic variant is an independent predictor of poor survival in patients with localized, but not metastatic disease. No significant financial relationships to disclose.