M Catherine Pietanza

Memorial Sloan-Kettering Cancer Center, New York, New York, United States

Are you M Catherine Pietanza?

Claim your profile

Publications (62)

  • M. Catherine Pietanza · Anya M. Litvak · Anna M. Varghese · [...] · Charles M. Rudin
    [Show abstract] [Hide abstract] ABSTRACT: The Hedgehog pathway has been implicated in small cell lung cancer (SCLC) tumor initiation and progression. Pharmacologic blockade of the key Hedgehog regulator, Smoothened, may inhibit these processes. We performed a phase I study to determine the maximum tolerated dose (MTD) of sonidegib (LDE225), a selective, oral Smoothened antagonist, in combination with etoposide/cisplatin in newly diagnosed patients with extensive stage SCLC.
    Article · Sep 2016
  • Martin Reck · Alexander Luft · Aleksandra Szczesna · [...] · David Spigel
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: Patients with extensive-stage disease small-cell lung cancer (SCLC) have poor survival outcomes despite first-line chemotherapy with etoposide and platinum. This randomized, double-blind phase III study evaluated the efficacy and safety of ipilimumab or placebo plus etoposide and platinum in patients with newly diagnosed extensive-stage disease SCLC. Patients and methods: Patients were randomly assigned at a ratio of one to one to receive chemotherapy with etoposide and platinum (cisplatin or carboplatin) plus ipilimumab 10 mg/kg or placebo every 3 weeks for a total of four doses each in a phased induction schedule (chemotherapy in cycles one to four; ipilimumab or placebo beginning in cycle three up to cycle six), followed by ipilimumab or placebo maintenance every 12 weeks. Primary end point was overall survival (OS) among patients receiving at least one dose of blinded study therapy. Results: Of 1,132 patients randomly assigned, 954 received at least one dose of study therapy (chemotherapy plus ipilimumab, n = 478; chemotherapy plus placebo, n = 476). Median OS was 11.0 months for chemotherapy plus ipilimumab versus 10.9 months for chemotherapy plus placebo (hazard ratio, 0.94; 95% CI, 0.81 to 1.09; P = .3775). Median progression-free survival was 4.6 months for chemotherapy plus ipilimumab versus 4.4 months for chemotherapy plus placebo (hazard ratio, 0.85; 95% CI, 0.75 to 0.97). Rates and severity of treatment-related adverse events were similar between arms, except for diarrhea, rash, and colitis, which were more frequent with chemotherapy plus ipilimumab. Rate of treatment-related discontinuation was higher with chemotherapy plus ipilimumab (18% v 2% with chemotherapy plus placebo). Five treatment-related deaths occurred with chemotherapy plus ipilimumab and two with chemotherapy plus placebo. Conclusion: Addition of ipilimumab to chemotherapy did not prolong OS versus chemotherapy alone in patients with newly diagnosed extensive-stage disease SCLC. No new or unexpected adverse events were observed with chemotherapy plus ipilimumab. Several ongoing studies are evaluating ipilimumab in combination with programmed death-1 inhibitors in SCLC.
    Article · Jul 2016 · Journal of Clinical Oncology
  • [Show abstract] [Hide abstract] ABSTRACT: Treatments for small-cell lung cancer (SCLC) after failure of platinum-based chemotherapy are limited. We assessed safety and activity of nivolumab and nivolumab plus ipilimumab in patients with SCLC who progressed after one or more previous regimens.
    Article · Jun 2016 · The Lancet Oncology
  • Natasha Rekhtman · M Catherine Pietanza · Matthew D Hellmann · [...] · Marc Ladanyi
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a highly aggressive neoplasm, whose biological relationship to small cell lung carcinoma (SCLC) versus non-SCLC (NSCLC) remains unclear, contributing to uncertainty regarding optimal clinical management. To clarify these relationships, we analyzed genomic alterations in LCNEC compared to other major lung carcinoma types. Experimental design: LCNEC (n=45) tumor/normal pairs underwent targeted next-generation sequencing of 241 cancer genes by MSK-IMPACT platform, and comprehensive histologic, immunohistochemical and clinical analysis. Genomic data were compared to MSK-IMPACT analysis of other lung carcinoma histologies (n=242). Results: Commonly altered genes in LCNEC included TP53 (78%), RB1 (38%), STK11 (33%), KEAP1 (31%) and KRAS (22%). Genomic profiles segregated LCNEC into 2 major and 1 minor subsets: SCLC-like (n=18), characterized by TP53+RB1 co-mutation/loss and other SCLC-type alterations, including MYCL amplification; NSCLC-like (n=25), characterized by the lack of co-altered TP53+RB1 and nearly-universal occurrence of NSCLC-type mutations (STK11, KRAS, KEAP1); and carcinoid-like (n=2), characterized by MEN1 mutations and low mutation burden. SCLC-like and NSCLC-like subsets revealed several clinicopathological differences, including higher proliferative activity in SCLC-like tumors (P<0.0001), and exclusive adenocarcinoma-type differentiation marker expression in NSCLC-like tumors (P=0.005). While exhibiting predominant similarity with lung adenocarcinoma, NSCLC-like LCNEC harbored several distinctive genomic alterations, including more frequent mutations in NOTCH family genes (28%), implicated as key regulators of neuroendocrine differentiation. Conclusions: LCNEC is a biologically-heterogeneous group of tumors, comprising distinct subsets with genomic signatures of SCLC, NSCLC (predominantly adenocarcinoma), and rarely, highly-proliferative carcinoids. Recognition of these subsets may inform the classification and management of LCNEC patients.
    Article · Mar 2016 · Clinical Cancer Research
  • Anya Litvak · M. Catherine Pietanza
    [Show abstract] [Hide abstract] ABSTRACT: Bronchial and thymic carcinoids are rare. We present epidemiologic data and potential risk factors. The approach to bronchial and thymic carcinoid patients is discussed, from the initial diagnosis and evaluations to treatment. These malignancies follow staging systems of their site of origin. Because bronchial and thymic carcinoids are rare, we use many treatment strategies that have been demonstrated in gastrointestinal and pancreatic neuroendocrine tumors. The lack of information regarding efficacy in bronchial and thymic carcinoids, as well as the scarcity of therapeutic options available, demands the importance of clinical trials that include these patients.
    Article · Feb 2016 · Hematology/Oncology Clinics of North America
  • Source
    Full-text Article · Jan 2016 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
  • Source
    Jarushka Naidoo · Maria L Santos-Zabala · Tunc Iyriboz · [...] · Maria C Pietanza
    [Show abstract] [Hide abstract] ABSTRACT: Background: Large cell neuroendocrine carcinoma (LCNEC) accounts for approximately 3% of lung cancers. Pathologic classification and optimal therapies are debated. We report the clinicopathologic features, treatment and survival of a series of patients with stage IV LCNEC. Materials and methods: Cases of pathologically-confirmed stage IV LCNEC evaluated at Memorial Sloan Kettering Cancer Center from 2006 to 2013 were identified. We collected demographic, treatment, and survival data. Available radiology was evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Results: Forty-nine patients with stage IV LCNEC were identified. The median age was 64 years, 63% of patients were male, and 88% were smokers. Twenty-three patients (n = 23/49; 47%) had brain metastases, 17 at diagnosis and 6 during the disease course. Seventeen LCNEC patients (35%) had molecular testing, of which 24% had KRAS mutations (n = 4/17). Treatment data for first-line metastatic disease was available on 37 patients: 70% (n = 26) received platinum/etoposide and 30% (n = 11) received other regimens. RECIST was completed on 23 patients with available imaging; objective response rate was 37% (95% confidence interval, 16%-62%) with platinum/etoposide, while those treated with other first-line regimens did not achieve a response. Median overall survival was 10.2 months (95% confidence interval, 8.6-16.4 months) for the entire cohort. Conclusion: Patients with stage IV LCNEC have a high incidence of brain metastases. KRAS mutations are common. Patients with stage IV LCNEC do not respond as well to platinum/etoposide compared with historic data for extensive stage small-cell lung cancer; however, the prognosis is similar. Prospective studies are needed to define optimum therapy for stage IV LCNEC.
    Full-text Article · Jan 2016 · Clinical Lung Cancer
  • S.A. Hayes · M.C. Pietanza · D. O'Driscoll · [...] · M.S. Ginsberg
    [Show abstract] [Hide abstract] ABSTRACT: To examine the correlations between uni-dimensional RECIST and volumetric measurements in patients with lung adenocarcinoma and to assess their association with overall survival (OS) and progression-free survival (PFS).
    Article · Jan 2016 · European Journal of Radiology
  • Ethan Basch · William A Wood · Deborah Schrag · [...] · M Catherine Pietanza
    [Show abstract] [Hide abstract] ABSTRACT: Background: Clinicians can miss up to half of patients' symptomatic toxicities in cancer clinical trials and routine practice. Although patient-reported outcome questionnaires have been developed to capture this information, it is unclear whether clinicians will make use of patient-reported outcomes to inform their own toxicity documentation, or to prompt symptom management activities. Methods: 44 lung cancer patients that participated in a phase 2 treatment trial self-reported 13 symptomatic toxicities derived from the National Cancer Institute's Common Terminology Criteria for Adverse Events and Karnofsky Performance Status via tablet computers in waiting areas immediately preceding scheduled visits. During visits, clinicians viewed patients' self-reported toxicity and performance status ratings on a computer interface and could agree or disagree/reassign grades ("shared" reporting). Agreement of clinicians with patient-reported grades was tabulated, and compared using weighted kappa statistics. Clinical actions in response to patient-reported severe (grade 3/4) toxicities were measured (e.g. treatment discontinuation, dose reduction, supportive medications). For comparison, 45 non-trial patients with lung cancer being treated in the same clinic by the same physicians were simultaneously enrolled in a parallel cohort study in which patients also self-reported toxicity grades but reports were not shared with clinicians ("non-shared" reporting). Results: Toxicities and performance status were reported by patients and reviewed by clinicians at (780/782) 99.7% of study visits in the phase 2 trial which used "shared" reporting. Clinicians agreed with patients 93% of the time with kappas 0.82-0.92. Clinical actions were taken in response to 67% of severe patient-reported toxicities. In the "non-shared" reporting comparison group, clinicians agreed with patients 56% of the time with kappas 0.04-0.48 (significantly worse than shared reporting for all symptoms), and clinical actions were taken in response to 44% of severe patient-reported toxicities. Conclusion: Clinicians will frequently agree with patient-reported symptoms and performance status, and will use this information to guide documentation and symptom management. (ClinicalTrials.gov: NCT00807573).
    Article · Nov 2015 · Clinical Trials
  • B.H. Lok · M.C. Pietanza · A. Foster · [...] · A.J. Wu
    Article · Nov 2015 · International journal of radiation oncology, biology, physics
  • Source
    Full-text Article · Nov 2015
  • Source
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: The American College of Chest Physicians (ACCP) produced an evidence-based guideline on treatment of patients with small-cell lung cancer (SCLC). Because of the relevance of this guideline to American Society of Clinical Oncology (ASCO) membership, ASCO reviewed the guideline, applying a set of procedures and policies used to critically examine guidelines developed by other organizations. Methods: The ACCP guideline on the treatment of SCLC was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel updated the literature search, reviewed the content, and considered additional recommendations. Results: The ASCO Endorsement Panel determined that the recommendations from the ACCP guideline, published in 2013, are clear, thorough, and based on current scientific evidence. ASCO endorses the ACCP guideline on the treatment of SCLC, with the addition of qualifying statements. Recommendations: Surgery is indicated for selected stage I SCLC. Limited-stage disease should be treated with concurrent chemoradiotherapy in patients with good performance status. Thoracic radiotherapy should be administered early in the course of treatment, preferably beginning with cycle one or two of chemotherapy. Chemotherapy should consist of four cycles of a platinum agent and etoposide. Extensive-stage disease should be treated primarily with chemotherapy consisting of a platinum agent plus etoposide or irinotecan. Prophylactic cranial irradiation prolongs survival in patients with limited-stage disease who achieve a complete or partial response to initial therapy and may do so in similarly responding patients with extensive-stage disease as well. Additional information is available at http://www.asco.org/endorsements/sclc and http://www.asco.org/guidelineswiki.
    Full-text Article · Sep 2015 · Journal of Clinical Oncology
  • M.C. Pietanza · D. Spigel · T.M. Bauer · [...] · S. Dylla
    Article · Sep 2015
  • Article · Sep 2015
  • [Show abstract] [Hide abstract] ABSTRACT: The high-grade pulmonary neuroendocrine tumors, small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), remain among the most deadly malignancies. Therapies that effectively target and kill tumor-initiating cells (TICs) in these cancers should translate to improved patient survival. Patient-derived xenograft (PDX) tumors serve as excellent models to study tumor biology and characterize TICs. Increased expression of delta-like 3 (DLL3) was discovered in SCLC and LCNEC PDX tumors and confirmed in primary SCLC and LCNEC tumors. DLL3 protein is expressed on the surface of tumor cells but not in normal adult tissues. A DLL3-targeted antibody-drug conjugate (ADC), SC16LD6.5, comprised of a humanized anti-DLL3 monoclonal antibody conjugated to a DNA-damaging pyrrolobenzodiazepine (PBD) dimer toxin, induced durable tumor regression in vivo across multiple PDX models. Serial transplantation experiments executed with limiting dilutions of cells provided functional evidence confirming that the lack of tumor recurrence after SC16LD6.5 exposure resulted from effective targeting of DLL3-expressing TICs. In vivo efficacy correlated with DLL3 expression, and responses were observed in PDX models initiated from patients with both limited and extensive-stage disease and were independent of their sensitivity to standard-of-care chemotherapy regimens. SC16LD6.5 effectively targets and eradicates DLL3-expressing TICs in SCLC and LCNEC PDX tumors and is a promising first-in-class ADC for the treatment of high-grade pulmonary neuroendocrine tumors. Copyright © 2015, American Association for the Advancement of Science.
    Article · Aug 2015 · Science translational medicine
  • Helen H. Won · M. Catherine Pietanza · Lee M. Krug · [...] · Michael F. Berger
    Article · Aug 2015 · Cancer Research
  • [Show abstract] [Hide abstract] ABSTRACT: Whether (18)F-fludeoxyglucose positron emission tomography (PET)/computed tomography (CT) metrics predict outcome in limited-stage (LS) small-cell lung cancer (SCLC) has not been well established; most previous reports have only analyzed maximal standardized uptake values (SUVmax). We investigated multiple pretreatment PET metrics, including SUVmax, mean SUV (SUVmean), total lesion glycolysis, and metabolic tumor volume (MTV) in LS-SCLC patients undergoing chemoradiotherapy (CRT) and correlated them with survival and disease control outcomes. All patients received platinum-based chemotherapy and a median radiation dose of 45 Gy. Kaplan-Meier and competing-risks analyses were performed to assess the prognostic value of PET metrics with respect to overall survival (OS), distant failure (DF), disease-free survival (DFS), and locoregional failure (LRF). Univariate and multivariate analyses were performed to account for the effect of other clinical factors on outcomes. A total of 120 patients with LS-SCLC had analyzable pre-CRT PET/CTs. The median follow up was 34 months. Median OS was 26.9 months. OS was 53.2% at 2 years and 33.1% at 5 years. SUVmax, SUVmean, MTV, and total lesion glycolysis of the primary tumor were not significantly associated with OS, LRF, and DFS on univariate analysis. MTV was significantly associated with DF (P = .024) on univariate but not multivariate analysis. This is the largest reported series to date evaluating the prognostic value of baseline PET metrics in LS-SCLC. Neither SUVmax nor other analyzed PET metrics demonstrated significant correlation with OS or LRF. MTV was correlated with DF and DFS, but this association was no longer significant after adjustment for other clinical factors. This analysis suggests that pretreatment PET scans, even with the use of advanced metrics, do not have independent prognostic value for outcomes in LS-SCLC patients after CRT. Copyright © 2015 Elsevier Inc. All rights reserved.
    Article · Aug 2015 · Clinical Lung Cancer
  • M Catherine Pietanza · Lauren Averett Byers · John D Minna · Charles M Rudin
    [Show abstract] [Hide abstract] ABSTRACT: Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy with a unique natural history characterized by a short doubling time, high growth fraction, and early development of widespread metastases. Although a chemotherapy- and radiation-sensitive disease, SCLC typically recurs rapidly after primary treatment, with only 6% of patients surviving 5 years from diagnosis. This disease has been notable for the absence of major improvements in its treatment: Nearly four decades after the introduction of a platinum-etoposide doublet, therapeutic options have remained virtually unchanged, with correspondingly little improvement in survival rates. Here, we summarize specific barriers and challenges inherent to SCLC research and care that have limited progress in novel therapeutic development to date. We discuss recent progress in basic and translational research, especially in the development of mouse models, which will provide insights into the patterns of metastasis and resistance in SCLC. Opportunities in clinical research aimed at exploiting SCLC biology are reviewed, with an emphasis on ongoing trials. SCLC has been described as a recalcitrant cancer, for which there is an urgent need for accelerated progress. The NCI convened a panel of laboratory and clinical investigators interested in SCLC with a goal of defining consensus recommendations to accelerate progress in the treatment of SCLC, which we summarize here. Clin Cancer Res; 21(10); 2244-55. ©2015 AACR. See all articles in this CCR Focus section, "Progress in Lung Cancer." ©2015 American Association for Cancer Research.
    Article · May 2015 · Clinical Cancer Research
  • Conference Paper · Feb 2015
  • M.C. Pietanza · L.M. Krug · A.J. Wu · [...] · W.D. Travis
    Chapter · Jan 2015