Validation of the Royal Marsden Hospital prognostic score in patients treated in the Phase I Clinical Trials Program at the MD Anderson Cancer Center

BACKGROUND:

The authors validated the Royal Marsden Hospital (RMH) prognostic score in patients with advanced lung, pancreatic, and head and neck cancers who were enrolled on phase 1 trials in the MD Anderson Cancer Center Phase I Clinical Trials Program.

METHODS:

The RMH score uses albumin (≥3.5 g/dL vs <3.5 g/dL), lactate dehydrogenase (less than or equal to the upper limit of normal [≤ULN] vs >ULN), and the number of metastatic sites (≤2 sites vs ≥3 sites) to predict patient survival in phase 1 trials. The authors of this report retrospectively reviewed the outcomes of 229 consecutive patients with lung, pancreatic, and head and neck tumors who were treated on 57 phase 1 trials.

RESULTS:

Two hundred twenty‐nine consecutive patients with lung cancer (N = 85), pancreatic cancer (N = 83), and head and neck tumors (N = 61) were treated. The median patient age was 60 years (range, 26‐85 years), and 63% of the patients were men. Patients with a good RMH prognostic score (0‐1) at baseline had a longer median survival than patients with a poor prognostic score (2‐3; 33.9 weeks vs 21.1 weeks; P < .0001). The RMH score was an independent variable that predicted survival in multivariate analysis. Other independent variables that predicted better survival were hemoglobin level (≥10.5 g/dL), Eastern Cooperative Oncology Group performance status (0‐1), and tumor type. Patients who were treated on first‐in‐human trials did not fare worse compared with those who were not treated on first‐in‐human trials.

CONCLUSIONS:

For patients with lung, pancreatic, and head and neck tumors who were treated on phase 1 trials, survival was predicted accurately by the RMH prognostic score. Cancer 2012;. © 2011 American Cancer Society.     

Outcomes in 144 Patients With Colorectal Cancer Treated in a Phase I Clinic: The MD Anderson Cancer Center Experience

BackgroundPatients with advanced colorectal cancer have a poor prognosis once standard therapies fail. This retrospective study presents the characteristics and outcomes in 144 patients treated in phase I clinical trials.MethodsWe retrospectively reviewed the clinical outcomes in 144 consecutive patients with colorectal cancer referred to the phase I clinic at MD Anderson.ResultsMedian age was 60 years (range, 35-86 years). The median number of previous systemic therapies was 4 (range, 1-7). The median PFS with the last line of conventional systemic treatment was 12.3 weeks (95% confidence interval [CI], 11.0-14.4); the median PFS of the best phase I treatment was shorter at 8.1 weeks (95% CI, 7.9-8.7 weeks; log-rank test, P < .0001). In the multivariate analysis that included the RMH score, sex (male vs. female, P = .02; hazard ratio [HR], 1.57), hemoglobin (< 10.5 vs. ≥ 10.5 g/dL; P = .03; HR 1.79), and the RMH score (2-3 vs. 0-1; P < .003; HR, 1.85) were significant predictors of poor survival. Conclusion: The PFS of patients with colorectal cancer in phase I treatment was shorter than it was on their last line of conventional systemic treatment. Multivariate analysis confirmed the value of the RMH score for predicting overall survival in patients with colorectal cancer enrolled in phase I studies.     

Clinical Outcomes of Patients With Breast Cancer in a Phase I Clinic: The M. D. Anderson Cancer Center Experience

PurposePatients with metastatic breast cancer (MBC) refractory to standard therapy have a poor prognosis. We assessed prognostic factors and clinical outcomes for patients with MBC referred to a phase I clinic focused primarily on targeted agents.Patients and MethodsWe reviewed the medical records of sequential patients with MBC who presented to our phase I clinic between September 2004 and May 2008 to assess baseline patient characteristics, overall survival (OS), and clinical benefit.ResultsA total of 92 patients were identified, with a median age of 53 years (range, 28–83 years). The median number of previous therapies was 5 (range, 1–16 therapies). Of 92 patients, 78 were eligible for and offered ≥ 1 phase I clinical trial. With a median follow-up of 7.4 months, the median OS was 6.7 months (95% CI, 5.2–9.7). In multivariate analysis, independent factors predicting shorter survival were ≥ 10 previous treatments (vs. < 10 previous treatments; hazard ratio [HR], 3.27; 95% CI, 1.37–7.81; P = .008), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2/3 (vs. 0/1; HR, 2.92; 95% CI, 1.28–6.66; P = .01), and albumin level < 3.5 g/dL (vs. > 3.5 g/dL; HR, 2.88; 95% CI, 1.41–5.89; P = .004).ConclusionPatients with locally advanced or metastatic breast cancer referred for our phase I studies had a median survival of 6.7 months. Heavily pretreated disease, poor ECOG PS, and/or low albumin levels were associated with significantly shorter survival in a multivariate analysis.     

Program Development for Supportive Care of Cancer Patients

No abstract available for this article.     

United States National Cancer Institute Radiotherapy Development Program

The United States National Cancer Institute (NCI) has long supported research in radiotherapy since its establishment by an act of Congress in 1937. One of the first grants for research awarded in 1938 was to support work in developing a cyclotron for conducting clinical research on therapeutic uses of neutrons and radioactive isotopes. Support for training cancer specialists was given high priority in the early days of NCI. In 1961, the Cancer Centers Program was instituted which included a radiation research program that became the primary source of grant support for radiotherapy clinical research centers in the US. There is a need for radiotherapy research because approximately 50-60% of people with newly diagnosed cancers will receive radiotherapy at some time during their disease. In 1979, the Radiotherapy Development Branch (RDP) assumed responsibility for all radiation program grants including radiation physics, radiobiology, and radiotherapy. The RDB manages a portfolio of grants and contracts with an annual budget of over $45 million. In fiscal year (FY) 1984, research support for individual investigator grants, program project grants, and contracts amounted to $22, 15, and 6 million, respectively. The accomplishments of NCI research grantees and contractors in radiotherapy-related areas have been considerable over the past 45 years. It is essential that NCI continue its commitment to radiotherapy research and development.     

Undergraduate Cancer Training Program for Underrepresented Students: Findings from a Minority Institution/Cancer Center Partnership

Students from racially/ethnically diverse backgrounds are underrepresented in graduate programs in biomedical disciplines. One goal of the Minority Institution/Cancer Center partnership between New Mexico State University (NMSU) and the Fred Hutchinson Cancer Research Center (FHCRC) is to expand the number of underrepresented students who are trained in cancer research. As part of the collaboration, a summer internship program has been organized at the FHCRC. The program runs for 9 weeks and involves mentored research, research seminars, coffee breaks, social activities, and a final poster session. This study examined the graduate school attendance rates of past interns, explored interns’ perceptions of the training program, and identified ways to improve the program. Thirty undergraduate students enrolled at NMSU participated in the internship program from 2002 to 2007 and telephone interviews were conducted on 22 (73%) of them. One-third of the students were currently in graduate school (32%); the remaining were either working (36%), still in undergraduate school (27%), or unemployed and not in school (5%). Students rated highly the following aspects of the program: mentored research, informal time spent with mentors, and research seminars. Students also reported the following activities would further enhance the program: instruction on writing a personal statement for graduate school and tips in choosing an advisor. Students also desired instruction on taking the GRE/MCAT, receiving advice on selecting a graduate or professional school, and receiving advice on where to apply. These findings can inform the design of internship programs aimed at increasing rates of graduate school attendance among underrepresented students.     

Thymoma Patients Treated in a Phase I Clinic at MD Anderson Cancer Center: Responses to mTOR Inhibitors and Molecular Analyses

BACKGROUND

Thymomas and thymic carcinoma are rare tumors with no approved therapies. Our purpose was to analyze the molecular features and outcomes of patients referred to the Clinical Center for Targeted Therapy (Phase I Clinic).

METHODS

We retrospectively reviewed the medical records of consecutive referred patients with advanced/metastatic thymoma or thymic carcinoma

RESULTS

Twenty-one patients were identified (median age 52 years; 10 women; median number of prior systemic therapies = 2). Six of 10 patients (60%) treated with mTOR inhibitor combination regimens achieved stable disease (SD) ≥12 months or a partial response (PR). For patients treated on mTOR inhibitor regimens (N = 10), median time to treatment failure (TTF) was 11.6 months versus 2.3 months on last conventional regimen prior to referral (p=0.024). Molecular analyses (performed by next generation sequencing in seven patients and single polymerase chain reaction (PCR)-based assays in an additional six patients) showed diverse actionable mutations: PIK3CA (1 of 12 tested; 8%); EGFR (1 of 13; 8%); RET (1 of 7; 14%); and AKT1 (1 of 7; 14%). Of two patients with PIK3CA or AKT1 mutations, one was treated with an mTOR inhibitor-based regimen and achieved 26% regression with a TTF of 17 months.

CONCLUSION

Patients with advanced/metastatic thymoma or thymic carcinoma demonstrated prolonged TTF on mTOR inhibitor-based therapy as compared to prior conventional treatment. Heterogeneity in actionable molecular aberrations was observed, suggesting that multi-assay molecular profiling and individualizing treatment merits investigation.     

Update on Phase I/II Breast Cancer Prevention Trials

The greatest success in breast cancer prevention has been with two agents, tamoxifen and raloxifene, both of which are approved by the US Food and Drug Administration (FDA) for the risk reduction of invasive breast cancer in high-risk women. However, these agents are only effective in preventing a certain percentage of estrogen receptor–positive disease. New agents are needed to prevent invasive breast cancer in a broader population of women. Phase I/II clinical trials are conducted with the intent of investigating agent efficacy via surrogate endpoint biomarkers. They also allow us to refine the population that may benefit from a given intervention. In this article, we review the important components of early phase trials including study design, cohort, surrogate endpoint biomarkers, and the challenges of recruiting to prevention trials. We discuss some early-phase trials for which results have recently been reported at meetings or through publications, as well as those trials that have recently been opened.     

Socioeconomic Disparities in Lung Cancer Treatment and Outcomes Persist Within a Single Academic Medical Center

BackgroundSocioeconomic disparities in treatment and outcomes of non–small-cell lung cancer (NSCLC) are well established. To explore whether these differences are secondary to individual or institutional characteristics, we examined treatment selection and outcome in a diverse population treated at a single medical center.Patients and MethodsWe performed a retrospective analysis of consecutive patients diagnosed with NSCLC stages I-III from 2000 to 2005 at the University of Texas Southwestern Medical Center. Treatment selection was dichotomized as ‘standard’ (surgery for stage I-II; surgery and/or radiation therapy for stage III) or ‘other.’ Associations between patient characteristics (including socioeconomic status) and treatment selection were examined using logistic regression; associations between characteristics and overall survival were examined using Cox regression models and Kaplan-Meier survival analysis.ResultsA total of 450 patients were included. Twenty-eight percent of patients had private insurance, 43% had Medicare, and 29% had an indigent care plan. The likelihood of receiving ‘standard’ therapy was significantly associated with insurance type (indigent plan versus private insurance odds ratio [OR] 0.13, 95% confidence interval [CI] 0.04, 0.43 for stage I-II; OR 0.38, 95% CI 0.14, 1.00 for stage III). For patients with stage I-II NSCLC, survival was associated with age, sex, insurance type (indigent plan versus private insurance hazard ratio for death 1.98; 95% CI 1.16, 3.37), stage, and treatment selection. In stage III NSCLC, survival was associated with treatment selection.ConclusionWithin a single academic medical center, socioeconomically disadvantaged patients with stage I-III NSCLC are less likely to receive ‘standard’ therapy. Socioeconomically disadvantaged patients with stage I-II NSCLC have inferior survival independent of therapy.     

Developing and Implementing an Advanced Communication Training Program in Oncology at a Comprehensive Cancer Center

Cancer patients report significant levels of unmet needs in the realm of communication. Communication skills training programs have been shown to improve clinical communication. However, advanced communication skills training programs in oncology have lacked institutional integration, and thus have not attended to institutional norms and cultures that may counteract explicit communication skills training. We developed and implemented an advanced communication skills training program made up of nine teaching modules for faculty, fellows, and residents. Training included didactic and experiential small group work. Self-efficacy and behavior change were assessed for individual participants. Since 2006, 515 clinicians have participated in this training program. Participants have shown significant gains in self-efficacy regarding communicating with patients in various contexts. Our initial work in this area demonstrates the implementation of such a program at a major cancer center to be feasible, to be acceptable, and to have a significant impact on participants' self-efficacy.     

Revisiting Clinical Trials Using EGFR Inhibitor-Based Regimens in Patients with Advanced Non-Small Cell Lung Cancer: A Retrospective Analysis of an MD Anderson Cancer Center Phase I Population

Purpose

Single-agent EGFR inhibitor therapy is effective mainly in patients with lung cancer and EGFR mutations. Treating patients who develop resistance, or who are insensitive from the outset, often because of resistant mutations, other aberrations or the lack of an EGFR mutation, probably requires rational combinations. We therefore investigated the outcome of EGFR inhibitor-based combination regimens in patients with heavily-pretreated non-small cell lung cancer (NSCLC) referred to a Phase I Clinic.

Methods

We reviewed the electronic records of patients with NSCLC treated with an EGFR inhibitor-based combination regimen: erlotinib and cetuximab; erlotinib, cetuximab and bevacizumab; erlotinib and dasatinib; erlotinib and bortezomib; or cetuximab and sirolimus.

Results

EGFR mutations were detected in 16% of patients (21/131). EGFR inhibitor-based combination regimens were administered to 15 patients with EGFR-mutant NSCLC and 24 with EGFR wild-type disease. Stable disease (SD) ≥6 months/partial remission (PR) was attained in 20% of EGFR-mutant patients (3/15; two with sensitive mutations and secondary resistance to prior erlotinib, and one with a resistant mutation), as well as 26% of evaluable patients (5/19) with wild-type disease. One of three evaluable patients with squamous cell histology achieved SD for 26.5 months (EGFR wild-type, TP53-mutant, regimen=erlotinib, cetuximab and bevacizumab).

Conclusions

Eight of 34 evaluable patients (24%) with advanced, refractory NSCLC evaluable for response achieved SD ≥6 months/PR (PR=3; SD ≥6 months=5) on EGFR inhibitor-based combination regimens (erlotinib, cetuximab; erlotinib, cetuximab and bevacizumab; and, erlotinib, bortezomib), including patients with secondary resistance to single-agent EGFR inhibitors, resistant mutations, wild-type disease, and, squamous histology.     

Phase I Trial of Anti-MET Monoclonal Antibody in MET-Overexpressed Refractory Cancer

Background

Samsung Advance Institute of Technology-301 (SAIT301) is a human immunoglobulin G2 antibody that can specifically target mesenchymal epithelial transition factor (c-MET). This novel antibody has higher priority over hepatocyte growth factors when binding to the Sema domain of c-MET and accelerates the internalization and degradation of c-MET, proving its powerful antitumor activities in intra- as well as extracellular areas.