Association of Quality-of-Life Outcomes in Cancer Drug Trials With Survival Outcomes and Drug Class.

Importance: Although quality of life (QOL) is an important clinical end point, cancer drugs are often approved based on overall survival (OS) or putative surrogate end points such as progression-free survival (PFS) without QOL data. Objective: To ascertain whether cancer drug trials that show improvement in OS or PFS also improve global QOL of patients with cancer compared with the control treatment, as well as to assess how unchanged or detrimental QOL outcomes are reported in trial publications. Design, Setting, and Participants: This retrospective cohort study included all patients with cancer in the advanced setting who were enrolled into phase 3 randomized clinical trials (RCTs) of cancer drugs reporting QOL data and published in English language in a PubMed-indexed journal in the calendar year 2019. The systematic search of PubMed was conducted in July 2020. Main Outcomes and Measures: Association of QOL outcomes with OS and PFS, framing of unchanged QOL outcomes in trial publications, and the association of favorable framing with industry funding of the trials. Results: A total of 45 phase 3 RCTs enrolling 24 806 participants (13 368 in the experimental arm and 11 438 in the control arm) met the inclusion criteria and were included in the study analyses. Improvement in global QOL with the experimental agent was reported in 11 (24%) RCTs. The RCTs with improved QOL were more likely to also show improved OS vs trials with unimproved QOL (7 of 11 [64%] trials vs 10 of 34 [29%] trials; χ2 = 4.13; P = .04); there was no such association observed for PFS (6 of 11 [55%] trials vs 17 of 34 [50%] trials, χ2 = 0.03; P = .87). Six trials reported worsening QOL, of which 3 (50%) were trials of targeted drugs, and 11 trials reported improvement in QOL, of which 6 (55%) were trials of immunotherapy drugs. Of the 34 trials in which QOL was not improved compared with controls, 16 (47%) reported these results in a positive frame, an observation statistically significantly associated with industry funding (χ2 = 6.35; P = .01). Conclusions and Relevance: In this cohort study, a small proportion of RCTs of cancer drugs showed benefit in global QOL with the experimental agent. These results showed an association between QOL benefit and OS benefit but no such association with PFS benefit. Trials that failed to show improved QOL often reported their QOL outcomes more favorably. Non-immunotherapy-targeted drugs led to worse QOL more often than did cytotoxic agents.

Tracking the Workforce 2020-2030: Making the Case for a Cancer Workforce Registry.

Existing literature has described the projected increase in cancer incidence and the associated deficiencies in the cancer workforce. However, there is currently a lack of research into the necessary policy and planning steps that can be taken to mitigate this issue. Herein, we review current literature in this space and highlight the importance of implementing oncology workforce registries. We propose the establishment of cancer workforce registries using the WHO Minimum Data Set for Health Workforce Registry by adapting the data set to suit the multidisciplinary nature of the cancer workforce. The cancer workforce registry will track the trends of the workforce, so that evidence can drive decisions at the policy level. The oncology community needs to develop and optimize methods to collect information for these registries. National cancer societies are likely to continue to lead such efforts, but ministries of health, licensing bodies, and academic institutions should contribute and collaborate.

Effect of Combined Immune Checkpoint Inhibition vs Best Supportive Care Alone in Patients With Advanced Colorectal Cancer: The Canadian Cancer Trials Group CO.26 Study.

Importance: Single-agent immune checkpoint inhibition has not shown activities in advanced refractory colorectal cancer (CRC), other than in those patients who are microsatellite-instability high (MSI-H). Objective: To evaluate whether combining programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition improved patient survival in metastatic refractory CRC. Design, Setting, and Participants: A randomized phase 2 study was conducted in 27 cancer centers across Canada between August 2016 and June 2017, and data were analyzed on October 18, 2018. Eligible patients had histologically confirmed adenocarcinoma of the colon or rectum; received all available standard systemic therapies (fluoropyrimidines, oxaliplatin, irinotecan, and bevacizumab if appropriate; cetuximab or panitumumab if RAS wild-type tumors; regorafenib if available); were aged 18 years or older; had adequate organ function; had Eastern Cooperative Oncology Group performance status of 0 or 1, and measurable disease. Interventions: We randomly assigned patients to receive either 75 mg of tremelimumab every 28 days for the first 4 cycles plus 1500 mg durvalumab every 28 days, or best supportive care alone (BSC) in a 2:1 ratio. Main Outcomes and Measures: The primary end point was overall survival (OS) and a 2-sided P<.10 was considered statistically significant. Circulating cell-free DNA from baseline plasma was used to determine microsatellite instability (MSI) and tumor mutation burden (TMB). Results: Of 180 patients enrolled (121 men [67.2%] and 59 women [32.8%]; median [range] age, 65 [36-87] years), 179 were treated. With a median follow-up of 15.2 months, the median OS was 6.6 months for durvalumab and tremelimumab and 4.1 months for BSC (hazard ratio [HR], 0.72; 90% CI, 0.54-0.97; P = .07). Progression-free survival was 1.8 months and 1.9 months respectively (HR, 1.01; 90% CI, 0.76-1.34). Grade 3 or 4 adverse events were significantly more frequent with immunotherapy (75 [64%] patients in the treatment group had at least 1 grade 3 or higher adverse event vs 12 [20%] in the BSC group). Circulating cell-free DNA analysis was successful in 168 of 169 patients with available samples. In patients who were microsatellite stable (MSS), OS was significantly improved with durvalumab and tremelimumab (HR, 0.66; 90% CI, 0.49-0.89; P = .02). Patients who were MSS with plasma TMB of 28 variants per megabase or more (21% of MSS patients) had the greatest OS benefit (HR, 0.34; 90% CI, 0.18-0.63; P = .004). Conclusions and Relevance: This phase 2 study suggests that combined immune checkpoint inhibition with durvalumab plus tremelimumab may be associated with prolonged OS in patients with advanced refractory CRC. Elevated plasma TMB may select patients most likely to benefit from durvalumab and tremelimumab. Further confirmation studies are warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02870920.

Real-world outcomes of FOLFIRINOX vs gemcitabine and nab-paclitaxel in advanced pancreatic cancer: A population-based propensity score-weighted analysis.

BACKGROUND: In Ontario, FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GnP) have been publicly funded for first-line unresectable locally advanced pancreatic cancer (uLAPC) or metastatic pancreatic cancer (mPC) since April 2015. We examined the real-world effectiveness and safety of FFX vs GnP for advanced pancreatic cancer, and in uLAPC and mPC. METHODS: Patients receiving first-line FFX or GnP from April 2015 to March 2017 were identified in the New Drug Funding Program database. Baseline characteristics and outcomes were obtained through the Ontario Cancer Registry and other population-based databases. Overall survival (OS) was assessed using Kaplan-Meier and weighted Cox proportional hazard models, weighted by the inverse propensity score adjusting for baseline characteristics. Weighted odds ratio (OR) for hospitalization and emergency department visits (EDV) were estimated from weighted logistic regression models. RESULTS: For 1130 patients (632 FFX, 498 GnP), crude median OS was 9.6 and 6.1 months for FFX and GnP, respectively. Weighted OS was improved for FFX vs GnP (HR = 0.77, 0.70-0.85). Less frequent EDV and hospitalization were observed in FFX (EDV: 67.8%; Hospitalization: 49.2%) than GnP (EDV: 77.7%; Hospitalization: 59.3%). More frequent febrile neutropenia-related hospitalization was observed in FFX (5.8%) than GnP (3.3%). Risk of EDV and hospitalization were significantly lower for FFX vs GnP (EDV: OR = 0.68, P = .0001; Hospitalization: OR = 0.76, P = .002), whereas the risk of febrile neutropenia-related hospitalization was significantly higher (OR = 2.12, P = .001). Outcomes for uLAPC and mPC were similar. CONCLUSION: In the real world, FFX had longer OS, less frequent all-cause EDV and all-cause hospitalization, but more febrile neutropenia-related hospitalization compared to GnP.

Correction to: RiseTx: testing the feasibility of a web application for reducing sedentary behavior among prostate cancer survivors receiving androgen deprivation therapy.

Following publication of the original article [1], the author has requested us to make a correction in the Results section of the Abstract and in the Discussion sections as explained below.

RiseTx: testing the feasibility of a web application for reducing sedentary behavior among prostate cancer survivors receiving androgen deprivation therapy.

BACKGROUND: Given the high levels of sedentary time and treatment-related side effects in prostate cancer survivors (PCS), interventions targeting sedentary behavior (SED) may be more sustainable compared to physical activity (PA). PURPOSE: To examine the feasibility of a web-based intervention (RiseTx) for reducing SED and increasing moderate-to-vigorous physical activity (MVPA) among PCS undergoing ADT. Secondary outcomes include changes in SED, MVPA, light intensity PA, and quality of life. METHODS: Forty-six PCS were recruited from two cancer centres in Toronto, Ontario, Canada between July 2015-October 2016. PCS were given an activity tracker (Jawbone), access to the RiseTx website program, and provided with a goal of increasing walking by 3000 daily steps above baseline levels over a 12-week period. A range of support tools were progressively released to reduce SED time (e.g., self-monitoring of steps) during the five-phase program. Objective measures of SED, MVPA, and daily steps were compared across the 12-week intervention using linear mixed models. RESULTS: Of the 46 PCS enrolled in the study, 42 completed the SED intervention, representing a 9% attrition rate. Measurement completion rates were 97 and 65% at immediately post-intervention and 12-week follow-up for all measures, respectively. Overall adherence was 64% for total number of logins (i.e., > 3 visits each week). Sample mean age was 73.2 ± 7.3 years, mean BMI was 28.0 ± 3.0 kg/m2, mean number of months since diagnosis was 93.6 ± 71.2, and 72% had ADT administered continuously. Significant reductions of 455.4 weekly minutes of SED time were observed at post-intervention (p = .005). Significant increases of + 44.1 for weekly minutes of MVPA was observed at immediately post-intervention (p = .010). There were significant increases in step counts of + 1535 steps from baseline to post-intervention (p < .001). CONCLUSIONS: RiseTx was successful in reducing SED and increasing MVPA in PCS. PCS were satisfied with the intervention and its components. Additional strategies may be needed though for maintenance of behavior change. The next step for RiseTx is to replicate these findings in a larger, randomized controlled trial that will have the potential for reducing sedentary time among PCS. TRIAL REGISTRATION: NCT03321149 (ClinicalTrials.gov Identifier).

Association Between Prognosis and Tumor Laterality in Early-Stage Colon Cancer.

IMPORTANCE: Recent data have suggested that disease biology and outcome of colon cancer may differ between right-sided and left-sided tumors. However, the literature on the prognostic value of tumor laterality is conflicting. OBJECTIVE: To explore differences in laterality based on disease characteristics and outcomes in a population-based cohort of early-stage colon cancer. DESIGN, SETTING, AND PARTICIPANTS: This investigation was a population-based retrospective cohort study of patients with early-stage colon cancer from the province of Ontario, Canada. Electronic records of treatment were linked to the Ontario Cancer Registry to identify all patients with colon cancer who underwent resection between January 1, 2002, and December 31, 2008. The date of the final analysis was October 20, 2016. The study population included a 25% random sample of all patients with resected stage I to III disease. Right-sided colon cancer was defined as any tumor arising in the cecum, ascending colon, hepatic flexure, or transverse colon. Left-sided colon cancer was defined as any tumor arising in the splenic flexure, descending colon, sigmoid colon, or rectosigmoid colon. MAIN OUTCOMES AND MEASURES: Overall survival (OS) and cancer-specific survival (CSS) measured from the time of resection. RESULTS: This study identified 6365 patients with early-stage colon cancer (48.7% [3098 of 6365] female). Their median age was 72 years, and 51.7% (3291 of 6365) had right-sided disease. Stage distribution was 18.3% (1163 of 6365) stage I, 38.4% (2446 of 6365) stage II, and 43.3% (2756 of 6365) stage III. Patients with right-sided colon cancer were more likely to be older (median age, 73 vs 70 years; P < .001) and female (54.4% [1790 of 3291] vs 42.6% [1308 of 3074], P < .001) and have greater comorbidity. Right-sided cancers were more likely to be T4 (19.2% [631 of 3291] vs 15.9% [490 of 3074], P < .001) and poorly differentiated (21.1% [695 of 3291] vs 9.6% [295 of 3074], P < .001) but less likely to be node positive (42.0% [1383 of 3291] vs 44.7% [1373 of 3074], P = .03) compared with left-sided disease. In adjusted analyses, there was no difference in long-term survival for right-sided compared with left-sided colon cancer: the hazard ratios were 1.00 (95% CI, 0.92-1.08) for OS and 1.00 (95% CI, 0.91-1.10) for CSS. These results were consistent when the survival analyses were restricted to stage III disease: the hazard ratios were 1.03 (95% CI, 0.93-1.14) for OS and 1.10 (95% CI, 0.97-1.24) for CSS. CONCLUSIONS AND RELEVANCE: In this population-based cohort of early-stage resected colon cancer, disease laterality was not associated with long-term OS or CSS.

High prevalence of potential drug-drug interactions in patients with castration-resistant prostate cancer treated with abiraterone acetate.

PURPOSE: Abiraterone acetate (AA), used to treat metastatic castration-resistant prostate cancer (mCRPC), inhibits androgen biosynthesis by blocking cytochrome P450 (CYP) 17A1. It also inhibits other cytochromes involved in the metabolism of various widely used medications. As such, there is presumably a high potential for drug-drug interactions (DDIs) that can diminish the efficacy of AA or concurrent medications, or increase the risk of DDI-related adverse events (AEs). However, the scale of AA-associated DDIs is currently unknown. METHODS: We conducted a retrospective review of pharmacy records and electronic patient charts to retrieve individual drug histories and on-treatment AEs of mCRPC patients beginning AA therapy in a tertiary care setting. Potential DDIs were analyzed using two commercial databases, Lexicomp and Micromedex. RESULTS: Eighty-four informative patients were identified. Sixty-five patients (77 %) and 44 patients (52 %) were flagged for one or more potential DDIs by the Lexicomp and Micromedex databases, respectively. One hundred eighty-four potential DDIs were identified overall, with a median of 1 DDI per patient in both databases. Possibly due to rigorous DDI screening before AA treatment initiation, we did not identify a definite instance of DDI-related AEs. CONCLUSIONS: The use of commercial DDI databases suggests a substantial risk of potentially consequential DDIs in mCRPC patients undergoing AA therapy. However, prospective investigations with larger patient populations are required to better establish the clinical relevance of these DDIs.

Cost-Effectiveness Analysis of Different Sequences of the Use of Epidermal Growth Factor Receptor Inhibitors for Wild-Type KRAS Unresectable Metastatic Colorectal Cancer.

PURPOSE: Patients with unresectable wild-type KRAS metastatic colorectal cancer benefit from fluoropyrimidines (FP), oxaliplatin (O), irinotecan (I), bevacizumab (Bev), and epithelial growth factor receptor inhibitors (EGFRI). The most cost-effective regimen remains unclear. METHODS: A Markov model was constructed to examine the costs and outcomes of three treatment strategies: strategy A (reference strategy): EGFRI monotherapy in third line ([3L]; ie, first-line [1L]: Bev + FOLFIRI [FP + I] or FOLFOX [FP + O]; second line [2L]: FOLFIRI/FOLFOX; 3L: EGFRI); strategy B: EGFRI and I in 3L (ie, 1L: Bev + FOLFIRI/FOLFOX; 2L: FOLFIRI/FOLFOX; 3L: EGFRI + I); and strategy C: EGFRI in 1L (ie, 1L: EGFRI + FOLFIRI/FOLFOX; 2L: Bev + FOLFIRI/FOLFOX; 3L: best supportive care). Efficacy data of the treatments were obtained from the literature. Health system resource use information was derived from chart review and the literature. Using Euro-QOL 5 Dimensions, utilities were obtained by surveying medical oncologists and costs from the Ontario Ministry of Health and the literature. The perspective of the Canadian public health care system was used over a 5-year time horizon with a 5% discount in 2012 Canadian dollars. RESULTS: All three strategies had similar efficacy, but strategy C was most expensive. The incremental cost-effectiveness ratios (ICERs) for strategies B and C compared with A were 119,623 and 3,176,591, respectively. The model was primarily driven by the acquisition cost of the drugs. Strategy B was most cost effective when the willingness-to-pay threshold was > $130,000 per quality-adjusted life-year. Sensitivity analysis showed that strategy C would be cost-effective only when the progression-free survival of EGFRI is better than Bev in 1L with hazard ratio < 0.23 at willingness-to-pay of $150,000 per quality-adjusted life-year. CONCLUSION: First-line use of EGFRI in metastatic colorectal cancer is not cost effective at its current pricing relative to Bev.

A Qualitative Study Exploring the Perceptions of Sedentary Behavior in Prostate Cancer Survivors Receiving Androgen-Deprivation Therapy.

PURPOSE/OBJECTIVES: To describe and understand the perceptions of sedentary behavior (SED) and the interests and preferences for a SED intervention of men on androgen-deprivation therapy (ADT) within a two-phase (formative and intervention research) feasibility study. RESEARCH APPROACH: Qualitative, descriptive. SETTING: Princess Margaret Cancer Centre and Odette Cancer Centre, both in Toronto, Ontario, Canada. PARTICIPANTS: 27 men on ADT. METHODOLOGIC APPROACH: Men were recruited from prostate cancer clinics. Nine focus groups were conducted from November 2013 to April 2014 until data saturation was reached. Probe questions assessed perceptions regarding SED and preferences for a mobile SED intervention. Data were transcribed verbatim, and a thematic analysis was conducted. FINDINGS: Twenty-seven men with a mean age of 73.5 years (SD = 8.1 years) volunteered for the study. Most men were aware of the health risks associated with SED, but most discussed SED in terms of increasing physical activity (PA). Many men were interested in a mobile application to reduce SED and expressed that the design should be easy to use, have an alerting function to interrupt sitting, have the ability to track and monitor PA levels, be tailored to the individual, and involve social support. CONCLUSIONS: These findings will inform the development and evaluation of a novel SED intervention to improve health outcomes in this population. INTERPRETATION: Oncology nurses may serve as a motivational factor in encouraging men on ADT to reduce SED.

Overcoming obstacles in accessing unfunded oral chemotherapy: physician experience and challenges.

PURPOSE: Previous studies have shown hematologists and medical oncologists may not accept the financial limits set by governing agencies on patient access to oral chemotherapy. The purpose of this study was to capture the methods physicians used to overcome barriers to accessing chemotherapeutic regimens for their patients. METHODS: A total of 640 medical oncologists and hematologists across Canada were surveyed using a 13-item Web-based survey tool. The survey was delivered by e-mail with three follow-up reminders. After a response period of 3 months, results were collated and analyzed with descriptive statistics. RESULTS: Of the 640 invitations, 568 were successfully delivered, and 183 responses were received (response rate, 32.0%). Among respondents, 101 treated solid malignancies (55.2%), 49 treated nonsolid malignancies (26.8%), and 33 treated both (18.0%). To overcome funding barriers, participating oncologists enrolled patients onto clinical trials (90.5%), used compassionate access programs (96.1%), and made special requests to government (91.8%). Other methods included writing false claims on forms to fit funding criteria for drugs (31.1%) and using leftover drug supplies (31.0%). Physicians felt their inability to obtain unfunded medications had a negative impact on their patients' clinical outcomes (56.0%) and psychosocial quality of life (73.0%). Only 28.5% of physicians contacted their governing body with concerns about oral chemotherapy funding. CONCLUSION: Canadian physicians use numerous methods to obtain unfunded oral chemotherapies, including falsifying claims on access forms and submitting special requests to government agencies. Further study is warranted to explore the disconnection between policymakers and physicians with regard to funding of oral chemotherapies.

Ethical challenges: managing oncology drug shortages.

This vignette highlights the ethical issues surrounding restricted access to oncology drugs caused by drug shortages. A review of selected literature and a framework for creating institutional guidelines for reacting to shortage is provided.

Less than ideal: how oncologists practice with limited drug access.

PURPOSE: To evaluate Canadian medical oncologists' perspectives on how barriers to accessing new expensive cancer drugs have affected their practice and their opinions on the drug approval and funding processes. METHODS: Canadian medical oncologists treating colorectal cancer (CRC) were surveyed by means of a self-administered, cross-sectional survey. RESULTS: Of the 164 eligible oncologists, there were 68 respondents (41.4% response rate). Only 29.4% of physicians felt they had been using the ideal first-line chemotherapy regimen for patients with metastatic CRC. Although all considered bevacizumab to be a component of the ideal first-line regimen, only 18% could use bevacizumab routinely, and less than half (44.8%) always discussed its role with their patients. In terms of accessing unfunded drugs, most physicians agreed that private payment should be allowed for drugs to be delivered at their own centers (76.1%) or private infusion clinics (52.2%). Ninety-seven percent of physicians reported major concerns about the drug approval and funding processes, and 85% of physicians supported the establishment of a national drug formulary. CONCLUSIONS: Canadian medical oncologists are struggling to provide optimal cancer care for their patients with metastatic CRC as a result of nonuniform access to preferred therapeutic drugs. In face of these challenges, physicians have had to use clinical trials and private infusion clinics and, at times, may avoid discussing drugs with limited access. Many oncologists are dissatisfied with the existing funding mechanism and approval processes and support private payment for unfunded drugs.

Variation and consternation: access to unfunded cancer drugs in Canada.

PURPOSE: New anticancer drugs are improving outcomes for patients with cancer but at significant cost, and some publically funded health care systems have chosen not to fund these medications. Accessing these unfunded drugs concerns patients, challenges their physicians, and raises important policy and legal issues. We assessed Canadian medical oncologists' access to and attitudes toward accessing unfunded intravenous cancer drugs. METHODS: Two hundred twenty-two Canadian medical oncologists outside of Québec were surveyed. RESULTS: Response rate was 62% (138 of 222). Respondents could access unfunded cancer drugs (49% at their government-funded hospitals; 70% at nongovernment-funded private infusion clinics), but access varied across the country. A majority of respondents (52% to 67%) were comfortable with accessing unfunded drugs in their own institutions and uncomfortable with accessing these drugs in private clinics in Canada or the United States (52% to 61%), but substantial minorities had opposing opinions. The majority of respondents felt all methods of accessing unfunded intravenous cancer drugs should be available (76% in their own center; 60% in private clinics) and used these methods to access these medications (81% in their own institution; 62% in private clinics). CONCLUSION: Access to effective but unfunded cancer drugs varies across Canada. Policymakers need to consider whether this is consistent with articulated values of the system and whether currently planned processes address these inconsistencies. Key stakeholders need to consider the merits of the different means of accessing these drugs to appropriately and fairly integrate access into publically funded health care systems like that of Canada and other systems like that of the United States, which could face similar limits in the future.

In a survey, marked inconsistency in how oncologists judged value of high-cost cancer drugs in relation to gains in survival.

Amid calls for physicians to become better stewards of the nation's health care resources, it is important to gain insight into how physicians think about the cost-effectiveness of new treatments. Expensive new cancer treatments that can extend life raise questions about whether physicians are prepared to make "value for money" trade-offs when treating patients. We asked oncologists in the United States and Canada how much benefit, in additional months of life expectancy, a new drug would need to provide to justify its cost and warrant its use in an individual patient. The majority of oncologists agreed that a new cancer treatment that might add a year to a patient's life would be worthwhile if the cost was less than $100,000. But when given a hypothetical case of an individual patient to review, the oncologists also endorsed a hypothetical drug whose cost might be as high as $250,000 per life-year gained. The results show that oncologists are not consistent in deciding how many months an expensive new therapy should extend a person's life before the cost of therapy is justified. Moreover, the benefit that oncologists demand from new treatments in terms of length of survival does not necessarily increase according to the price of the treatment. The findings suggest that policy makers should find ways to improve how physicians are educated on the use of cost-effectiveness information and to influence physician decision making through clinical guidelines that incorporate cost-effectiveness information.

American society of clinical oncology statement: toward individualized care for patients with advanced cancer.

Patients with advanced incurable cancer face complex physical, psychological, social, and spiritual consequences of disease and its treatment. Care for these patients should include an individualized assessment of the patient's needs, goals, and preferences throughout the course of illness. Consideration of disease-directed therapy, symptom management, and attention to quality of life are important aspects of quality cancer care. However, emerging evidence suggests that, too often, realistic conversations about prognosis, the potential benefits and limitations of disease-directed therapy, and the potential role of palliative care, either in conjunction with or as an alternative to disease-directed therapy, occur late in the course of illness or not at all. This article addresses the American Society of Clinical Oncology's (ASCO's) vision for improved communication with and decision making for patients with advanced cancer. This statement advocates an individualized approach to discussing and providing disease-directed and supportive care options for patients with advanced cancer throughout the continuum of care. Building on ASCO's prior statements on end-of-life care (1998) and palliative care (2009), this article reviews the evidence for improved patient care in advanced cancer when patients' individual goals and preferences for care are discussed. It outlines the goals for individualized care, barriers that currently limit realization of this vision, and possible strategies to overcome these barriers that can improve care consistent with the goals of our patients and evidence-based medical practice.

A phase II, multicenter study of cetuximab monotherapy in patients with refractory, metastatic colorectal carcinoma with absent epidermal growth factor receptor immunostaining.

PURPOSE: To determine antitumor activity of cetuximab monotherapy in patients with refractory metastatic colorectal carcinoma (mCRC) with lack of specific membrane immunostaining for the epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: Patients had immunohistochemical (IHC)-determined mCRC with absent EGFR immunostaining that progressed after receiving at least one standard, fluoropyrimidine-containing chemotherapeutic regimen. Absent EGFR immunostaining was defined as the IHC absence of specific membrane staining in ≥500 cancer cells examined in well-preserved tissue. The study was performed prior to results of studies linking cetuximab sensitivity to K-ras mutation status. Patients received 400 mg/m(2) of intravenous (i.v.) cetuximab followed by once-weekly i.v. cetuximab 250 mg/m(2) until disease progression or unacceptable toxicity. Patients were evaluated for objective response at least every 6 weeks. Kaplan-Meier estimates were calculated for duration of response, time to progression (TTP), and overall survival (OS). RESULTS: Seven (8.2%) of 85 mCRC patients whose tumors lacked EGFR immunostaining had major responses following cetuximab treatment. The median duration of response was 5.1 months. Median TTP and OS were 2.5 months and 10.0 months, respectively; the 1-year survival rate was 39.6%. The most frequently reported cetuximab-related adverse events were acneiform dermatitis, fatigue, headache, and dry skin. CONCLUSION: Cetuximab monotherapy produces objective antitumor activity in patients with mCRC that does not express EGFR as determined by IHC. The activity and safety profiles of cetuximab monotherapy in mCRC lacking EGFR immunostaining are similar to previous observations in EGFR IHC-positive disease that was not selected based on K-ras mutation status.

Continental Divide? The attitudes of US and Canadian oncologists on the costs, cost-effectiveness, and health policies associated with new cancer drugs.

PURPOSE: Oncologists in the United States and Canada work in different health care systems, but physicians in both countries face challenges posed by the rising costs of cancer drugs. We compared their attitudes regarding the costs and cost-effectiveness of medications and related health policy. METHODS: Survey responses of a random sample of 1,355 United States and 238 Canadian medical oncologists (all outside of Québec) were compared. RESULTS: Response rate was 59%. More US oncologists (67% v 52%; P < .001) favor access to effective treatments regardless of cost, while more Canadians favor access to effective treatments only if they are cost-effective (75% v 58%; P < .001). Most (84% US, 80% Canadian) oncologists state that patient out-of-pocket costs influence their treatment recommendations, but less than half the respondents always or frequently discuss the costs of treatments with their patients. The majority of oncologists favor more use of cost-effectiveness data in coverage decisions (80% US, 69% Canadian; P = .004), but fewer than half the oncologists in both countries feel well equipped to use cost-effectiveness information. Majorities of oncologists favor government price controls (57% US, 68% Canadian; P = .01), but less than half favor more cost-sharing by patients (29% US, 41% Canadian; P = .004). Oncologists in both countries prefer to have physicians and nonprofit agencies determine whether drugs provide good value. CONCLUSION: Oncologists in the United States and Canada generally have similar attitudes regarding cancer drug costs, cost-effectiveness, and associated policies, despite practicing in different health care systems. The results support providing education to help oncologists in both countries use cost-effectiveness information and discuss drug costs with their patients.