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Open Access Publications from the University of California

Scholarly Works (6 results)

  • Article
  • Peer Reviewed
UC Irvine Previously Published Works (2017)
    Cover page: Highlights from the Gynecologic Oncology Track at the 2017 Annual Meeting of the American Society of Clinical OncologyCreative Commons 'BY' version 4.0 license
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2018)

    Introduction

    Though cervical cytology, HPV DNA testing, and pre-invasive disease management has significantly reduced the number of new diagnoses of cervical cancer, women with persistent oncogenic HPV infection are at significant risk for developing invasive cervical cancer. Early stage and locally advanced disease can be cured, but women with advanced or recurrent disease have a very poor prognosis. This underscores the need for different treatment strategies for advanced cervical cancer, the most promising of which are novel therapeutics that target the ability of HPV to overcome host immune tolerance. Areas covered: This review includes new therapies being investigated for the treatment of recurrent, metastatic or refractory cervical cancer, separated into broad categories of cellular and non-cellular based strategies. Expert opinion: Advanced and recurrent cervical cancer has a poor prognosis, prompting investigations into the development of strategies that will eradicate tumor and/or overcome host immunologic tolerance of disease. It is unknown whether it will be these strategies alone or a combination of treatment modalities that will ultimately provide the best outcomes; nevertheless, the new data are promising.
      Cover page: Rational design for cervical cancer therapeutics: cellular and non-cellular based strategies on the horizon for recurrent, metastatic or refractory cervical cancer
      • Thesis
      • Peer Reviewed
      UC Irvine Electronic Theses and Dissertations (2018)

      Background: The greatest clinical obstacle in advanced ovarian cancer remains acquired drug resistance, indicative of the absence of effective maintenance therapies. We evaluated cost-effectiveness of available maintenance strategies for advanced ovarian cancer, adjusting for pre-treatment medication costs, infusion center charges, and costs of managing adverse events.

      Methods: Toxicity and median PFS data were attained from the registration trials for a) paclitaxel (GOG 212); b) bevacizumab (GOG 218, ICON 7, OCEANS, GOG 213); c) niraparib (NOVA), olaparib (SOLO-2), rucaparib (ARIEL-3), and d) pembrolizumab. Since bevacizumab was investigated in different patient populations, each trial was modeled separately. Checkpoint inhibition phase III randomized trials in ovarian cancer are not mature, thus data for pembrolizumab (available via agnostic indication) was obtained from the phase IB ovarian cohort of KEYNOTE-028. Utilizing a Markov model, patients transitioned through health states of response, hematological and non-hematological complications, progression, and death. Using Medicare data, the costs of pretreatment testing, infusions, and managing toxicities were estimated. To compare the therapies, incremental cost-effectiveness ratios (ICER) and quality of adjusted life-months gained were calculated.

      Results: Seemingly, the most cost-effective was maintenance paclitaxel at $1,329 /PFS month. Expected costs of PARP inhibitors (PARPi(s)) prior to progression were approx. $510,387 (20.3x paclitaxel, 7.5x pembrolizumab, and 2.6-3.2x bevacizumab). Comparing pembrolizumab to PARPi(s) in BRCA-deficient patients, the immunotherapy maintenance therapy generated ICERs per month of life gained of $23,055 (niraparib), $25,622 (rucaparib), and $28,465 (olaparib).

      Conclusion: Employing PFS as the benchmark, high costs of maintenance PARPi(s) are not abated by adjusting for the sequelae that occurs with maintenance chemotherapy and anti-angiogenic therapy. The current trend to study novel combinations is challenging when considering economic toxicity and the burden it places on our patients.

        Cover page: Cost-Effectiveness of Maintenance Therapy in Advanced Ovarian Cancer: Paclitaxel, Bevacizumab, Niraparib, Olaparib, Rucaparib, And PembrolizumabCreative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2018)

        Introduction

        Though cervical cytology, HPV DNA testing, and pre-invasive disease management has significantly reduced the number of new diagnoses of cervical cancer, women with persistent oncogenic HPV infection are at significant risk for developing invasive cervical cancer. Early stage and locally advanced disease can be cured, but women with advanced or recurrent disease have a very poor prognosis. This underscores the need for different treatment strategies for advanced cervical cancer, the most promising of which are novel therapeutics that target the ability of HPV to overcome host immune tolerance. Areas covered: This review includes new therapies being investigated for the treatment of recurrent, metastatic or refractory cervical cancer, separated into broad categories of cellular and non-cellular based strategies. Expert opinion: Advanced and recurrent cervical cancer has a poor prognosis, prompting investigations into the development of strategies that will eradicate tumor and/or overcome host immunologic tolerance of disease. It is unknown whether it will be these strategies alone or a combination of treatment modalities that will ultimately provide the best outcomes; nevertheless, the new data are promising.
          Cover page: Rational design for cervical cancer therapeutics: cellular and non-cellular based strategies on the horizon for recurrent, metastatic or refractory cervical cancer.Creative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2020)
          BACKGROUND:Olaparib was approved on December 19, 2014 by the US FDA as 4th-line therapy (and beyond) for patients with germline BRCA1/2 mutations; rucaparib was approved on December 19, 2016 as 3rd-line therapy (and beyond) for germline or somatic BRCA1/2-mutated recurrent disease. On October 23, 2019, niraparib was approved for treatment of women with damaging mutations in BRCA1/2 or other homologous recombination repair genes who had been treated with three or more prior regimens. We compared the cost-effectiveness of PARPi(s) with intravenous regimens for platinum-resistant disease. METHODS:Median progression-free survival (PFS) and toxicity data from regulatory trials were incorporated in a model which transitioned patients through response, hematologic complications, non-hematologic complications, progression, and death. Using TreeAge Pro 2017, each PARPi(s) was compared separately to non‑platinum-based and bevacizumab-containing regimens. Costs of IV drugs, managing toxicities, infusions, and supportive care were estimated using 2017 Medicare data. Incremental cost-effectiveness ratios (ICERs) were calculated and PFS was reported in quality adjusted life months for platinum-resistant populations. RESULTS:Non‑platinum-based intravenous chemotherapy was most cost effective ($6,412/PFS-month) compared with bevacizumab-containing regimens ($12,187/PFS-month), niraparib ($18,970/PFS-month), olaparib ($16,327/PFS-month), and rucaparib ($16,637/PFS-month). ICERs for PARPi(s) were 3-3.5× times greater than intravenous non‑platinum-based regimens. CONCLUSION:High costs of orally administered PARPi(s) were not mitigated or balanced by costs of infusion and managing toxicities of intravenous regimens typically associated with lower response and shorter median PFS. Balancing modest clinical benefit with costs of novel therapies remains problematic and could widen disparities among those with limited access to care.
            Cover page: Cost-effectiveness of niraparib, rucaparib, and olaparib for treatment of platinum-resistant, recurrent ovarian carcinomaCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2020)
            BACKGROUND: Olaparib was approved on December 19, 2014 by the US FDA as 4th-line therapy (and beyond) for patients with germline BRCA1/2 mutations; rucaparib was approved on December 19, 2016 as 3rd-line therapy (and beyond) for germline or somatic BRCA1/2-mutated recurrent disease. On October 23, 2019, niraparib was approved for treatment of women with damaging mutations in BRCA1/2 or other homologous recombination repair genes who had been treated with three or more prior regimens. We compared the cost-effectiveness of PARPi(s) with intravenous regimens for platinum-resistant disease. METHODS: Median progression-free survival (PFS) and toxicity data from regulatory trials were incorporated in a model which transitioned patients through response, hematologic complications, non-hematologic complications, progression, and death. Using TreeAge Pro 2017, each PARPi(s) was compared separately to non‑platinum-based and bevacizumab-containing regimens. Costs of IV drugs, managing toxicities, infusions, and supportive care were estimated using 2017 Medicare data. Incremental cost-effectiveness ratios (ICERs) were calculated and PFS was reported in quality adjusted life months for platinum-resistant populations. RESULTS: Non‑platinum-based intravenous chemotherapy was most cost effective ($6,412/PFS-month) compared with bevacizumab-containing regimens ($12,187/PFS-month), niraparib ($18,970/PFS-month), olaparib ($16,327/PFS-month), and rucaparib ($16,637/PFS-month). ICERs for PARPi(s) were 3-3.5× times greater than intravenous non‑platinum-based regimens. CONCLUSION: High costs of orally administered PARPi(s) were not mitigated or balanced by costs of infusion and managing toxicities of intravenous regimens typically associated with lower response and shorter median PFS. Balancing modest clinical benefit with costs of novel therapies remains problematic and could widen disparities among those with limited access to care.
              Cover page: Cost-effectiveness of niraparib, rucaparib, and olaparib for treatment of platinum-resistant, recurrent ovarian carcinoma.
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