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Background: Little is known regarding associations between peripheral blood biomarkers (PBBMs) and survival, response, and toxicity in recurrent/metastatic head and neck squamous cell carcinomas (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs). Methods: In this single‐institution retrospective cohort study, a dataset of patients with R/M HNSCC treated with ICIs between 08/2012–03/2021 was established, including demographic and clinicopathologic characteristics. Pretreatment PBBMs were collected and evaluated for associations with grade ≥3 adverse events (G ≥ 3AE) by CTCAEv5, objective response (ORR) by RECIST 1.1, overall survival (OS), and progression‐free survival (PFS). Multivariable models for each outcome were created using elastic net variable selection. Results: Our study included 186 patients, with 51 (27%) demonstrating complete or partial response to immunotherapy. Multivariable models adjusted for ECOG performance status (PS), p16, and smoking demonstrated that pretreatment higher LDH and absolute neutrophils, as well as lower percent lymphocytes correlated with worse OS and PFS. Higher LDH and lower % lymphocytes also correlated with worse ORR. Conclusions: In the largest study to date examining PBBMs in ICI‐treated R/M HNSCCs, our variable selection method revealed PBBMs prognostic for survival and response to immunotherapy. These biomarkers warrant further investigation in a prospective study along with validation with CPS biomarker. [ABSTRACT FROM AUTHOR]

Background: Associations between peripheral blood biomarkers and oncologic outcomes were explored in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HN) and salivary gland cancer (SGC) treated with pembrolizumab and vorinostat on a phase II trial (NCT02538510). Experimental Design: Twenty‐five HN and 25 SGCs were treated with pembrolizumab and vorinostat. Baseline peripheral blood was available in 21 HN and 20 SGCs and evaluated for associations with grade ≥3 adverse events (G ≥ 3AE) by CTCAEv4, objective response rate (ORR), overall survival (OS), and progression‐free survival (PFS). Results: Higher pretreatment neutrophil‐to‐lymphocyte ratio (NLR) and neutrophils, as well as lower pretreatment lymphocytes and T helper cells correlated with worse OS and PFS. Higher NLR further predicted increased rates of G ≥ 3AEs. No correlations with ORR were observed. Conclusions: In a prospectively evaluated cohort of HN and SGCs treated with pembrolizumab and vorinostat, we observed novel associations between peripheral blood biomarkers and oncologic outcomes and toxicities. [ABSTRACT FROM AUTHOR]

Background: Anti‐PD1 checkpoint inhibitors (ICI) represent an established standard‐of‐care for patients with recurrent/metastatic head and neck squamous cell carcinoma (RMHNSCC). Landmark studies excluded patients with ECOG performance status (PS) ≥2; the benefit of ICI in this population is therefore unknown. Methods: We retrospectively reviewed RMHNSCC patients who received 1+ dose of ICI at our institution between 2013 and 2019. Demographic and clinical data were obtained; the latter included objective response (ORR), toxicity, and any unplanned hospitalization (UH). Associations were explored using uni‐ and multivariate analysis. Overall survival (OS) was estimated using a Cox proportional hazards model; ORR, toxicity, and UH were evaluated with logistic regression. Results: Of the 152 patients, 29 (19%) had an ECOG PS ≥2. Sixty‐six (44%) experienced toxicity; 54 (36%) had a UH. A multivariate model for OS containing PS, smoking status, and HPV status demonstrated a strong association between ECOG ≥2 and shorter OS (p < 0.001; HR = 3.30, CI = 2.01–5.41). An association between OS and former (vs. never) smoking was also seen (p < 0.001; HR = 2.17, CI = 1.41–3.35); current smoking did not reach statistical significance. On univariate analysis, poor PS was associated with inferior ORR (p = 0.03; OR = 0.25, CI = 0.06–0.77) and increased UH (p = 0.04; OR = 2.43, CI = 1.05—5.71). There was no significant association between toxicity and any patient characteristic. Conclusions: We observed inferior OS, ORR, and rates of UH among ICI‐treated RMHNSCC patients with ECOG 2/3. Our findings help frame discussion of therapeutic options in this poor‐risk population. [ABSTRACT FROM AUTHOR]

PURPOSE Time from diagnosis to treatment has been associated with worse survival outcomes in non-small-cell lung cancer (NSCLC). However, little is known about the impact of delay in time to diagnosis. We aimed to evaluate the impact of time from radiographic suspicion to histologic diagnosis on survival outcomes using the US SEER-Medicare population database. METHODS We identified patients from the SEER-Medicare data set diagnosed with any stage NSCLC between January 1, 2011, and December 31, 2015, who received stage-appropriate treatment and had a computed tomography scan within 1 year of diagnosis. Time to confirmation was determined as the interval between most recent computed tomography imaging and date of histologic diagnosis. Our primary outcome was overall survival (OS). RESULTS In total, 10,824 eligible patients were identified. The median time to confirmation was 20 (range 0-363) days. Using multivariate Cox regression models, longer time to confirmation was associated with improved OS in all comers driven by stage IV patients after adjustment for age, sex, diagnosis year, histology, and comorbidity index. In a separate landmark analysis excluding patients deceased within 6 months of diagnosis, the association between time to diagnosis and survival was no longer evident. CONCLUSION Time to confirmation of NSCLC was inversely associated with OS in this US SEER population study. This association was lost when patients deceased within 6 months of diagnosis were excluded, suggesting that retrospective registry-claims databases may not be the optimal data source to study time to diagnosis as a quality metric because of the unaccounted confounding effects of tumor behavior. Prospective evaluations of clinically enriched data sources may better serve this purpose. [ABSTRACT FROM AUTHOR]

A study was conducted to examine the impact of motesanib diphosphate in progressive differentiated thyroid cancer. Results revealed that motesanib diphosphate could cause partial responses in patients.

Background/Objective: End-of-life health care utilization (EOLHCU) is largely uncharacterized among patients with recurrent/metastatic head and neck squamous cell carcinomas (RMHNSCC), particularly now that immune checkpoint inhibitors (ICI) have been introduced to the treatment landscape. We examined this in a single-institution, retrospective study. Design/Settings: We utilized a database of deceased, ICI-treated RMHNSCC patients to obtain demographic and EOLHCU data, the latter of which included advanced care plan documentation (ACPD) and systemic therapy or emergency room (ER)/hospital/intensive care unit (ICU) admission within 30 days of death (DOD). This was compared with a cohort of deceased thoracic malignancy (TM) patients in an exploratory analysis. Multivariate analysis was performed to examine for association between patient factors (such as age, Eastern Cooperative Oncology Group (ECOG) performance status, or smoking status) and overall survival (OS); associations between the said patient factors and EOLHCU were also evaluated. This study was conducted at an academic, tertiary center in the United States. Results: The RMHNSCC patients (n = 74) were more likely to have ACPD (p < 0.01), an emergency department visit (p < 0.01), and/or hospital admission (p < 0.01) within 30 DOD relative to the TM group. There was no difference in ICU admissions, ICU deaths, or systemic therapy at end of life (EOL). The OS declined in association with ECOG performance status (PS) and smoking. No association was observed between patient factors and any EOLHCU metric. Conclusions: At our center, patients with ICI-treated RMHNSCC have higher rates of both ACPD and EOLHCU, suggesting high symptom burden and representing opportunities for further study into supportive care augmentation. [ABSTRACT FROM AUTHOR]

PURPOSE: The costs associated with clinical trial enrollment remain uncertain. We hypothesized that trial participation is associated with decreased total direct medical costs to health care payers in metastatic non--small-cell lung cancer. METHODS: In this retrospective cohort study, we linked clinical data from electronic medical records to sociodemographic data from a cancer registry and claims data from Medicare and two private insurance plans. We used a difference-in-difference analysis to estimate mean per patient per month total direct medical costs for patients enrolled on a second-line (2L) trial versus patients receiving standard-of-care 2L systemic therapy. RESULTS: Among 70 eligible patients, the difference-in-difference of mean per patient per month total direct medical costs between 2L trial participants and nonparticipants was --$6,663 (P = .01), for a mean savings of $45,308 per patient for the duration of 2L trial therapy. In a secondary analysis by primary insurance payer, this difference-in-difference was --$5,526 (P = .26) for patients with commercial insurance and --$7,432 (P = .01) for patients with Medicare. CONCLUSION: Participation in a 2L trial was associated with a $6,663 per month cost savings to health care payers for the duration of trial participation. Further studies are necessary to elucidate differences in cost savings from trial participation for Medicare and commercial payers. If confirmed, these results support health care payer investment in programs to improve clinical trial access and enrollment. [ABSTRACT FROM AUTHOR]

Abstract Background In non-small cell lung cancer (NSCLC), interstitial hypertension is a barrier to chemotherapy delivery, and is mediated by platelet derived growth factor receptor (PDGFR). Antagonizing PDGFR with imatinib may improve intra-tumoral delivery of paclitaxel, increasing response rate (RR). Methods This single-stage, open-label phase II study evaluated pulse dose imatinib and weekly paclitaxel in elderly patients with advanced NSCLC. Eligible patients were aged ≥ 70 with untreated, stage IIIB-IV NSCLC and ECOG performance status 0-2. Primary endpoint was RR. Secondary endpoints included median progression free and overall survival (PFS, OS) and correlatives of PDGFR pathway activation. Baseline Charlson Comorbidity Index (CCI) and Vulnerable Elder Survey-13 (VES-13) were correlated with outcomes. Results Thirty-four patients with median age 75 enrolled. Eleven of 29 (38%) were frail by VES-13 score. Overall RR was 11/34 (32%; 95% CI 17%-51%), meeting the primary endpoint. Median PFS and OS were 3.6 and 7.3 months, respectively. High tumoral PDGF-B expression predicted inferior PFS. Frail patients by VES-13 had significantly worse median PFS (3.2 vs. 4.5 months; p=0.02) and OS (4.8 vs. 12 months; p=0.02) than non-frail. Conclusions The combination of imatinib and paclitaxel had encouraging activity as measured by the primary endpoint of RR. However, PFS and OS were typical for elderly patients treated with single agent chemotherapy and the regimen is not recommended for further study. Adjunct imatinib did not overcome the established association of tumoral PDGF-B expression with inferior PFS. VES-13 was a powerful predictor of poor survival outcomes. Frailty should be further studied as a predictor of non-benefit from chemotherapy. Trial Registration ClinicalTrials.gov NCT01011075

The article presents a study on patient-reported quality of life (PRQOL) for head and neck cancer patients, focusing on racial disparities in the results. It looks at how scores were different before and after chemoradiation before examining why black patients had lower PRQOL scores and survival rates.

Since the beginning of the 21st century, the treatment of lung cancer has changed dramatically. New treatments are improving survival outcomes for patients but have led to dramatic increases in cost. In a value‐based payment system, patients should have access to comprehensive outcome measurements, including survival rates, quality of life, and cost. High value in cancer care will optimize the outcomes that matter to patients relative to cost. [ABSTRACT FROM AUTHOR]

Background. Paclitaxel is not considered to be an active drug in adenoid cystic carcinoma (ACC) of the salivary glands. We report 2 consecutive cases of patients with ACC who responded to paclitaxel. Methods. The patients were: (1) a 58-year-old man with recurrent ACC who developed pulmonary metastases, had progressive disease after a good response to first-line chemotherapy, and then achieved a partial response to weekly single- agent paclitaxel; and (2) a 46-year-old woman with extensive thoracic ACC metastases who achieved a significant response after 2 cycles of paclitaxel chemotherapy. Results. The first patient died of progressive disease approximately 4 months after completing paclitaxel therapy, and the second patient had disease control after 6 cycles of paclitaxel. Conclusions. Systemic weekly paclitaxel produced a significant response in 2 patients with ACC of the head and neck, and its use in this disease merits further study. © 2007 Wiley Periodicals, Inc. Head Neck, 2008 [ABSTRACT FROM AUTHOR]

Purpose: We sought to examine the prognostic value of fluorodeoxyglucose-positron emission tomography (PET) imaging during chemoradiation for unresectable non-small cell lung cancer for survival and hypothesized that tumor PET response is correlated with peripheral T-cell function., Methods and Materials: Forty-five patients with American Joint Committee on Cancer version 7 stage IIB-IIIB non-small cell lung cancer enrolled in a phase II trial and received platinum-doublet chemotherapy concurrent with 6 weeks of radiation (NCT02773238). Fluorodeoxyglucose-PET was performed before treatment start and after 24 Gy of radiation (week 3). PET response status was prospectively defined by multifactorial radiologic interpretation. PET responders received 60 Gy in 30 fractions, while nonresponders received concomitant boosts to 74 Gy in 30 fractions. Peripheral blood was drawn synchronously with PET imaging, from which germline DNA sequencing, T-cell receptor sequencing, and plasma cytokine analysis were performed., Results: Median follow-up was 18.8 months, 1-year overall survival (OS) 82%, 1-year progression-free survival 53%, and 1-year locoregional control 88%. Higher midtreatment PET total lesion glycolysis was detrimental to OS (1 year 87% vs 63%, P < .001), progression-free survival (1 year 60% vs 26%, P  = .044), and locoregional control (1 year 94% vs 65%, P  = .012), even after adjustment for clinical/treatment factors. Twenty-nine of 45 patients (64%) were classified as PET responders based on a priori definition. Higher tumor programmed death-ligand 1 expression was correlated with response on PET ( P  = .017). Higher T-cell receptor richness and clone distribution slope were associated with improved OS ( P  = .018-0.035); clone distribution slope was correlated with PET response ( P  = .031)., Conclusions: Midchemoradiation PET imaging is prognostic for survival; PET response may be linked to tumor and peripheral T-cell biomarkers., (© 2021 The Authors.)

Objectives The change in tumor fluorodeoxyglucose (FDG) uptake by positron emission tomography (PET) scan after one cycle of platinum-based chemotherapy has been shown to predict progression-free and overall survival (PFS and OS) among advanced non-small cell lung cancer (NSCLC) patients. Using early FDG-PET response to determine subsequent chemotherapy, we aim to evaluate the role that adaptive chemotherapy regimens have on later CT response, PFS, and OS in patients with advanced NSCLC. Materials and Methods Chemotherapy-naïve patients with metastatic NSCLC received carboplatin and paclitaxel (CP) on day one and repeated FDG-PET on day 18. PET-responding patients continued CP chemotherapy for a total of four cycles. PET non-responders were switched to alternate docetaxel and gemcitabine (DG) for three additional cycles. The primary outcome was the CT Response Evaluation Criteria in Solid Tumors (RECIST 1.0) response. Secondary endpoints included PFS and OS. Results  Forty-six patients initiated treatment with chemotherapy on trial and were evaluable by PET/CT. Of these, 19 (41%) met the FDG-PET criteria for the response after a single cycle of CP. Only one non-responding patient had a CT response. Despite the lack of CT response in the DG arm, no trend for worse PFS or OS was seen between the two arms. Conclusions This work demonstrates that changing chemotherapy in the event of non-response by PET did not lead to improved CT RECIST response. However, non-responding patients who switched chemotherapy had similar PFS and OS to those who responded by PET and continued the same regimen., Competing Interests: Hubert Vesselle - received consultant fees on image display software for MIM Software Inc., (Copyright © 2021, Eaton et al.)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates in immunotherapy. For the 2020 update, all of the systemic therapy regimens have been categorized using a new preference stratification system; certain regimens are now recommended as "preferred interventions," whereas others are categorized as either "other recommended interventions" or "useful under certain circumstances."

Purpose: As Toll-like receptors (TLR) are key mediators of immune responses, TLR agonists may be important for augmenting the efficacy of therapies for squamous cell carcinoma of the head and neck (SCCHN). Motolimod (VTX-2337), a selective small-molecule agonist of TLR8, stimulates natural killer (NK) cells, dendritic cells, and monocytes. A phase Ib clinical trial assessed the safety and antitumor activity of motolimod in combination with cetuximab in patients with SCCHN. Correlative biomarkers of immune activity were explored. Experimental Design: Thirteen patients with recurrent or metastatic SCCHN were enrolled in this open-label, dose-escalation study using a standard 3 + 3 design. Doses of motolimod (2.5, 3.0, or 3.5 mg/m 2 ) were given on days 1, 8, and 15, in combination with fixed weekly doses of cetuximab in 28-day cycles. Results: There were no protocol-defined dose-limiting toxicities, drug-related deaths, or evidence of synergistic toxicities between motolimod and cetuximab. Clinical tolerability at the 3.5 mg/m 2 dose level was not optimal for repeated dosing and 3.0 mg/m 2 was identified as the MTD. Two patients achieved partial responses for an overall response rate of 15%. Five patients had disease stabilization equating to a disease control rate of 54%. Statistically significant increases in plasma cytokines and in the frequency and activation of circulating NK cells were observed. Conclusions: Motolimod can be safely administered in combination with cetuximab with an acceptable toxicity profile. Encouraging antitumor activity and robust pharmacodynamic responses were observed. Motolimod is being further investigated in a phase II trial in patients with SCCHN (ClinicalTrials.gov ID: NCT01836029). Clin Cancer Res; 23(10); 2442-50. ©2016 AACR ., (©2016 American Association for Cancer Research.)

Purpose: Positive results of phase I studies evaluating lenvatinib in solid tumors, including thyroid cancer, prompted a phase II trial in advanced medullary thyroid carcinoma (MTC)., Experimental Design: Fifty-nine patients with unresectable progressive MTC per Response Evaluation Criteria In Solid Tumors (RECIST) v1.0 within the prior 12 months received lenvatinib (24-mg daily, 28-day cycles) until disease progression, unmanageable toxicity, withdrawal, or death. Prior anti-VEGFR therapy was permitted. The primary endpoint was objective response rate (ORR) by RECIST v1.0 and independent imaging review., Results: Lenvatinib ORR was 36% [95% confidence interval (CI), 24%-49%]; all partial responses. ORR was comparable between patients with (35%) or without (36%) prior anti-VEGFR therapy. Disease control rate (DCR) was 80% (95% CI, 67%-89%); 44% had stable disease. Among responders, median time to response (TTR) was 3.5 months (95% CI, 1.9-3.7). Median progression-free survival (PFS) was 9.0 months (95% CI, 7.0-not evaluable). Common toxicity criteria grade 3/4 treatment-emergent adverse events included diarrhea (14%), hypertension (7%), decreased appetite (7%), fatigue, dysphagia, and increased alanine aminotransferase levels (5% each). Ret proto-oncogene status did not correlate with outcomes. Low baseline levels of angiopoietin-2, hepatocyte growth factor, and IL8 were associated with tumor reduction and prolonged PFS. High baseline levels of VEGF, soluble VEGFR3, and platelet-derived growth factor BB, and low baseline levels of soluble Tie-2, were associated with tumor reduction., Conclusions: Lenvatinib had a high ORR, high DCR, and a short TTR in patients with documented progressive MTC. Toxicities were managed with dose modifications and medications., (©2015 American Association for Cancer Research.)

Salivary gland malignant tumors represent a diverse group of neoplasms. Their low incidence makes research studies challenging, with most therapeutic recommendations based on case reviews, single-arm trials, or small randomized trials. The standard of care for localized disease is surgical resection. Radiotherapy is the preferred local therapy when surgery is not possible or if there is significant morbidity. When symptomatic metastatic disease develops, systemic therapy is considered. Recent trial accrual success with a cooperative group, treatments based on defined molecular targets, and the development of immunotherapies all hold promise in improving the care of patients with these tumors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Although there once was a single algorithm for the treatment of patients with advanced lung cancer, the modern treatment of advanced lung cancer has multiple treatment pathways that depend on multiple factors, including histology and molecular subtype of disease. New molecular targets, targeted agents, and modes of therapy for patients, including immunotherapy, are being identified at an accelerating pace. These advances are changing outcomes and the treatment landscape, but they also highlight situations with inadequate data to support the use of cytotoxic chemotherapy. In this article, we provide an overview of data regarding cytotoxic chemotherapy and targeted therapy and their value after second line, review the critical role of supportive care and palliative care, and emphasize the importance of advance care planning with our patients. Although this article focuses primarily on NSCLC, the comments about palliative care and advanced care planning also apply to patients with small cell lung cancer.

Patients with confirmed stage IIIA non-small cell lung cancer (NSCLC) represent a very heterogeneous group which includes those with limited microscopic ipsilateral mediastinal lymph node involvement discovered after a surgical resection, as well as those who have radiologically evident bulky subcarinal lymph node involvement at presentation. Different therapeutic options in stage IIIA disease include neoadjuvant chemo- or chemoradiotherapy followed by surgery, primary surgery followed by adjuvant chemotherapy with or without sequential adjuvant radiation therapy or definitive chemoradiation without surgery. The roles of surgery and radiation in stage IIIA disease are controversial, and there is inadequate data from randomized trials to inform the optimal therapeutic strategy. In contrast, chemotherapy has a clear indication in the curative setting. Data from randomized trials indicates that cisplatin-based chemotherapy should be given in either adjuvant or neoadjuvant settings to patients who are undergoing curative surgical resection and who are candidates for cisplatin therapy. In definitive chemoradiotherapy, cisplatin-based therapy is recommended although a carboplatin-based regimen may be given if patients cannot receive cisplatin. Finally, all patients with stage IIIA NSCLC should be evaluated early in a multidisciplinary setting that includes medical and radiation oncologists and thoracic surgeons with experience in lung cancer therapy.

Patients with stage IIIA non-small cell lung cancer, determined based on involvement of ipsilateral mediastinal lymph nodes, represent the most challenging management problem in this disease. Patients with this stage disease may have very different degrees of lymph node involvement. The pathologic confirmation of this involvement is a key step in the therapeutic decision. The difference in the degree of lymph node compromise has prognostic and treatment implications. Based on multiple considerations, patients can be treated with induction chemotherapy, chemoradiotherapy followed by surgery, or definitive chemoradiotherapy without surgery. Data derived from clinical trials have provided incomplete guidance for physicians and their patients. The best therapeutic plan is achieved through the multidisciplinary cooperation of a team specialized in lung cancer.

Purpose: IPI-504 is a novel, water-soluble, potent inhibitor of heat-shock protein 90 (Hsp90). Its potential anticancer activity has been validated in preclinical in vitro and in vivo models. We studied the activity of IPI-504 after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy in patients with advanced, molecularly defined non-small-cell lung cancer (NSCLC)., Patients and Methods: Patients with advanced NSCLC, prior treatment with EGFR TKIs, and tumor tissue available for molecular genotyping were enrolled in this prospective, nonrandomized, multicenter, phase II study of IPI-504 monotherapy. The primary outcome was objective response rate (ORR). Secondary aims included safety, progression-free survival (PFS), and analysis of activity by molecular subtypes., Results: Seventy-six patients were enrolled between December 2007 and May 2009 from 10 United States cancer centers. An ORR of 7% (five of 76) was observed in the overall study population, 10% (four of 40) in patients who were EGFR wild-type, and 4% (one of 28) in those with EGFR mutations. Although both EGFR groups were below the target ORR of 20%, among the three patients with an ALK gene rearrangement, two had partial responses and the third had prolonged stable disease (7.2 months, 24% reduction in tumor size). The most common adverse events included grades 1 and 2 fatigue, nausea, and diarrhea. Grade 3 or higher liver function abnormalities were observed in nine patients (11.8%)., Conclusion: IPI-504 has clinical activity in patients with NSCLC, particularly among patients with ALK rearrangements.

Purpose: We conducted a phase II study to assess the efficacy of continuous dosing of sunitinib in patients with flurodeoxyglucose positron emission tomography (FDG-PET)-avid, iodine-refractory well-differentiated thyroid carcinoma (WDTC) and medullary thyroid cancer (MTC) and to assess for early response per FDG-PET., Experimental Design: Patients had metastatic, iodine-refractory WDTC or MTC with FDG-PET-avid disease. Sunitinib was administered at 37.5 mg daily on a continuous basis. The primary end point was response rate per Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included toxicity, overall survival, and time to progression. We conducted an exploratory analysis of FDG-PET response after 7 days of treatment., Results: Thirty-five patients were enrolled (7 MTC, 28 WDTC), and 33 patients were evaluable for disease response. The primary end point, objective response rate per RECIST, was 11 patients (31%; 95% confidence interval, 16-47%). There were 1 complete response (3%), 10 partial responses (28%), and 16 patients (46%) with stable disease. Progressive disease was seen in 6 patients (17%). The median time to progression was 12.8 months (95% confidence interval, 8.9 months-not reached). Repeat FDG-PET was done on 22 patients. The median percent change in average standardized uptake values was -11.7%, -13.9%, and 8.6% for patients with RECIST response, stable disease, and progressive disease, respectively. Differences between response categories were statistically significant (P = 0.03). The most common toxicities seen included fatigue (11%), neutropenia (34%), hand/foot syndrome (17%), diarrhea (17%), and leukopenia (31%). One patient on anticoagulation died of gastrointestinal bleeding., Conclusion: Continuous administration of sunitinib was effective in patients with iodine-refractory WDTC and MTC. Further study is warranted., (©2010 AACR.)

Recent trials have shown a benefit with maintenance therapy after 4 to 6 cycles of chemotherapy. These trials have shown improvement in progression-free survival using agents approved as second-line therapy in non-small cell lung cancer. Trials using erlotinib and pemetrexed showed improvement in overall survival. Consideration of trial design is critical for the interpretation of these results. Data on quality of life and cost have not been presented, but will ultimately be important in evaluating the usefulness of these approaches.

Purpose: This phase II study investigated the efficacy and tolerability of motesanib, an investigational, highly selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit in advanced medullary thyroid cancer (MTC)., Patients and Methods: Patients with locally advanced or metastatic, progressive or symptomatic MTC received motesanib 125 mg/d orally for up to 48 weeks or until unacceptable toxicity or disease progression. The primary end point was objective response by independent review. Other end points included duration of response, progression-free survival, safety, pharmacokinetics, and changes in tumor markers., Results: Of 91 enrolled patients who received motesanib, two (2%) achieved objective response (95% CI, 0.3% to 7.7%); their duration of response was 32 weeks (censored) and 21 weeks (disease progressed). Eighty-one percent of patients had stable disease (48% had durable stable disease > or = 24 weeks), 8% had disease progression as best response, and 9% were not evaluated; 76% experienced a decrease from baseline in target lesion measurement. Median progression-free survival was 48 weeks (95% CI, 43 to 56 weeks). Among patients with tumor marker analysis, 69 (83%) of 83 and 63 (75%) of 84 had decreased serum calcitonin and carcinoembryonic antigen during treatment, respectively, compared with baseline. The most common treatment-related adverse events were diarrhea (41%), fatigue (41%), hypothyroidism (29%), hypertension (27%), and anorexia (27%). In pharmacokinetic analyses, motesanib trough concentrations were lower compared with differentiated thyroid cancer patients from the same study., Conclusion: Although the objective response rate was low, a significant proportion of MTC patients (81%) achieved stable disease while receiving motesanib.