Progression-free Survival Decreases with Each Subsequent Therapy in Patients Presenting for Phase I Clinical Trials

Bailey, Christopher H.; Jameson, Gayle; Sima, Chao; Fleck, Sharon; White, Erica; Hoff, Daniel D. Von; Weiss, Glen J.

doi:10.7150/jca.3.7

Cited by 32 publications

(24 citation statements)

References 70 publications

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“…Previous reports of studies of phase I trials of patients with gynecologic cancers receiving targeted therapies have shown that PFS is either shorter or, in some cases, comparable to the PFS duration achieved on prior conventional therapies [48, 49]. However, in the present study 26% of patients receiving MTB-based therapy experienced PFS durations similar to or longer than those experienced on prior therapy; some of these were ongoing.…”

Section: Discussioncontrasting

confidence: 49%

Use of comprehensive genomic profiling to direct point-of-care management of patients with gynecologic cancers

Rodrı́guez-Rodrı́guez

Hirshfield

Rojas

et al. 2016

Gynecologic Oncology

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OBJECTIVE To determine the feasibility and clinical utility of using comprehensive genomic profiling (CGP) in the course of clinical care to identify clinically relevant tumor genomic alterations for patients with either rare or refractory gynecologic cancers to facilitate point-of-care management. Use of an expert, multidisciplinary, institutional molecular tumor board (MTB) assessment is discussed regarding input on putative targeted options for individualized therapy. METHODS A prospective clinical trial is ongoing. We report on the initial 69 patients with gynecologic cancers that were either rare or refractory to standard therapy. CGP was performed by Foundation Medicine, Inc. Genomic alterations were reviewed by members of an MTB. Consensus recommendations on genomically targeted, FDA-approved, on- and off-label therapies and clinical trials were sent to the treating physician, and decisions and outcomes were assessed. RESULTS Study outcomes were available for 64 patients. The mean number of genes altered per tumor was 4.97 (median=4; range, 1–26), and the average turnaround time from testing laboratory report to generation of formal recommendations was approximately three weeks. Evaluation of genomic and clinical data by the MTB led to generation of targeted treatment options in all 64 patients, and the percentage of patients for whom one or more of these recommendations were implemented by the treating physician was 39%. Seventy percent of the patients receiving targeted therapy based on a CGP result experienced radiologic response or showed evidence of clinical benefit or stable disease. CONCLUSION These data suggest that an institutional MTB is a feasible venue for reviewing tumor genomic profiling results and generating clinical recommendations. These data also support the need for further studies and guidelines on clinical decision making with greater availability of broad genomically based diagnostics.

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Section: Discussioncontrasting

confidence: 49%

Use of comprehensive genomic profiling to direct point-of-care management of patients with gynecologic cancers

Rodrı́guez-Rodrı́guez

Hirshfield

Rojas

et al. 2016

Gynecologic Oncology

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“…When patients are treated with platinum-based therapies, consideration of these times leads to the designation of patients as platinum sensitive, resistant or refractory [9]; this status is believed to be correlated with future response to platinum therapy. Noting that, in advanced cancers, the TFI decreases in subsequent treatments for patients treated serially with systemic therapies [10], response to platinum is expected to decay, perhaps due to drug selection forces [11]. …”

Section: Introductionmentioning

confidence: 99%

Prognostic factors modifying the treatment-free interval in recurrent ovarian cancer

Eng

Hanlon

Bradley

et al. 2015

Gynecologic Oncology

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Objectives While primary treatment for high-grade serous ovarian cancer tends to be uniform – maximal debulking and platinum/taxane adjuvant chemotherapy – there is little standardization of treatment in the recurrent setting beyond the exhaustive use of platinum therapies. Using secondary data from multiple centers participating in the Cancer Genome Atlas study (TCGA), we seek to characterize clinical features, timing and serial response data to provide empirical evidence for treatment expectations in the recurrent setting. Methods We conducted a retrospective survival analysis of TCGA study primary and secondary patient chemotherapy regimens by characterizing the dynamics of 1119 lines of therapy comprising the treatment of 461 high-grade serous ovarian cancer patients. All patients with post-surgical drug therapy information from the TCGA database were included in this study. Results A complete response to adjuvant therapy led to longer overall survival, but did not affect treatment free intervals (TFI) after relapse of disease. A strong predictor of the TFI on the next treatment regimen was the previous TFI with a decaying effect. The number of previous treatments, of platinum treatments, and the length of time from surgery all have an exponentially decreasing effect on TFI. Re-treatment times appear to cluster at predictable times following surgery. Conclusions While patients experience a consistent reduction in TFI with increasing re-treatment, the initial adjuvant interval is unrelated to later interval lengths. Platinum re-treatment remained an effective option in patients typically thought to be platinum resistant and the timing of monitoring visits may drive overall re-treatment patterns.

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“…Compared with patients who have other solid tumors, patients with MBC have a larger number of therapeutic options available. 17 The likelihood of response and prolonged tumor control is highest with the first line of chemotherapy, with limited data on the efficacy of later lines of chemotherapy despite its very common use in clinical practice. [18][19][20] Few data also ex-ist regarding the impact of tumor subtype on the likelihood of benefit with later lines of treatment.…”

Section: Introductionmentioning

confidence: 99%

Use and Duration of Chemotherapy in Patients With Metastatic Breast Cancer According to Tumor Subtype and Line of Therapy

Seah¹,

Vaz-Luís²,

Macrae³

et al. 2014

J Natl Compr Canc Netw

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Benefits of chemotherapy vary in patients with metastatic breast cancer (MBC). This article describes the impact of tumor subtype and the line of therapy on the duration of chemotherapy. Clinicopathologic characteristics were extracted from the medical records of 199 consecutive patients with MBC at Dana-Farber Cancer Institute and analyzed according to subtype. Tumor subtypes were classified as hormone receptor (HR)-positive, triple-negative (TNBC), or HER2-amplified breast cancer. Duration of chemotherapy of each line was defined as the start of a chemotherapy regimen to the start of the next line of therapy as a result of progression or toxicity. There were 96, 44, and 59 patients with HR(+), TNBC, and HER2-amplified breast cancer, respectively. Median age at MBC diagnosis was 53 years. Median overall survivals were 32 and 54 months for HER2-amplified disease, 36 months for HR(+) breast cancer, and 17 months for TNBC (P<.0001). Patients with HER2-amplified disease received the most lines (median, 4; P=.032) and the longest duration of chemotherapy for every line. The median duration of chemotherapy in HER2-amplified patients remained at more than 4 months even out to sixth-line therapy. Patients with TNBC tended to receive the shortest duration of chemotherapy for every line of therapy. Tumor subtypes influence the number of lines, duration of chemotherapy, and survival. Among patients with HR(+) and HER2-amplified disease who undergo chemotherapy beyond the third line, substantial rates of prolonged therapies suggest clinical benefit. The role of advanced (greater than third) chemotherapy lines in improving survival of all patients with MBC warrants further study.

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Progression-free Survival Decreases with Each Subsequent Therapy in Patients Presenting for Phase I Clinical Trials

Cited by 32 publications

References 70 publications

Use of comprehensive genomic profiling to direct point-of-care management of patients with gynecologic cancers

Use of comprehensive genomic profiling to direct point-of-care management of patients with gynecologic cancers

Prognostic factors modifying the treatment-free interval in recurrent ovarian cancer

Use and Duration of Chemotherapy in Patients With Metastatic Breast Cancer According to Tumor Subtype and Line of Therapy

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