Early disease progression and treatment discontinuation in patients with advanced ovarian cancer receiving immune checkpoint blockade

Boland, Julia L.; Zhou, Qin; Martin, Mitchell; Callahan, Margaret K.; Konner, Jason; O’Cearbhaill, Roisin E.; Friedman, Claire F.; Tew, William P.; Makker, Vicky; Grisham, Rachel N.; Hensley, Martee L.; Zecca, Nicholas; Iasonos, Alexia; Snyder, Alexandra; Hyman, David M.; Sabbatini, Paul; Aghajanian, Carol; Cadoo, Karen A.; Zamarin, Dmitriy

doi:10.1016/j.ygyno.2018.11.025

Cited by 39 publications

(34 citation statements)

References 38 publications

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“…36 Our results are valuable in that the discrepancy in MSI/MMR status may be among the mechanisms of resistance to anti-PD-1 therapy. Although peritoneal metastasis is associated with early treatment discontinuation in patients with ovarian cancer receiving anti-PD-1 treatment, 41 it remains unknown whether this correlation exists in patients with CRC. Theoretically, once the MSI status was inconsistent, the immune microenvironment including tumor-infiltrating lymphocytes changed concordantly, as found in our study.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Mismatch Repair Status Between Primary and Matched Metastatic Sites in Patients With Colorectal Cancer

Wang¹,

Wang

et al. 2019

Journal of the National Comprehensive Cancer Network

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Background: Differences between the features of primary cancer and matched metastatic cancer have recently drawn attention in research. This study investigated the concordance in microsatellite instability (MSI) and mismatch repair (MMR) status between primary and corresponding metastatic colorectal cancer (CRC). Methods: Consecutive patients with metastatic CRC who had both primary and metastatic tumors diagnosed at our institution in January 2008 through December 2016 were identified. Immunohistochemistry was used to test the MMR status of both primary and matched metastatic tumors, and PCR analysis was performed to test MSI in patients with deficient MMR (dMMR) status. Results: A total of 369 patients were included. Of the 46 patients with MSI-high primary tumors, 37 (80.4%) also had MSI-high metastatic tumors, whereas 9 (19.6%) had microsatellite stable (MSS) metastatic tumors. A high concordance was found in patients with liver, lung, or distant lymph node metastases. Interestingly, the discrepancy was more likely to be limited to peritoneal (5/20) or ovarian (4/4) metastasis (chi-square test, P<.001). These organ-specific features were also found in the pooled analysis. Along with the change of MSI-high in primary cancer to MSS in metastatic cancer, lymphocyte infiltration decreased significantly (P=.008). However, the change did not influence survival; the median overall survival of MSI-high and MSS metastatic tumors was 21.3 and 21.6 months, respectively (P=.774). The discrepancy rate was 1.6% for patients with proficient MMR primary tumors. Conclusions: For patients with dMMR primary tumors, the concordance of MSI and MMR status in primary CRC and corresponding metastatic cancer is potentially organ-specific. High concordance is found in liver, lung, and distant lymph node metastases, whereas discrepancy is more likely to occur in peritoneal or ovarian metastasis. Rebiopsy to evaluate MSI-high/dMMR status might be needed during the course of anti–PD-1 therapy in cases of peritoneal or ovarian metastasis.

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Section: Discussionmentioning

confidence: 99%

Comparison of Mismatch Repair Status Between Primary and Matched Metastatic Sites in Patients With Colorectal Cancer

Wang¹,

Wang

et al. 2019

Journal of the National Comprehensive Cancer Network

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“…In some cases, the disease develops faster than expected and in a more aggressive manner after immune checkpoint targeting immunotherapy. This phenomenon, designated as hyperprogressive disease (HPD), corresponds to a paradoxical boost in tumor growth under treatment and has been described in non-squamous non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), urothelial bladder carcinoma, hepatocellular carcinoma, gastric cancer, and anorectal melanoma (6)(7)(8)(9)(10)(11)(12)(13)(14), with a rate ranging between 4 and 29%. There are currently few data explaining the occurrence of HPD or allowing clinicians to identify patients at risk of developing HPD.…”

Section: Introductionmentioning

confidence: 99%

How Can Immune Checkpoint Inhibitors Cause Hyperprogression in Solid Tumors?

et al. 2020

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Following the administration of immune checkpoint inhibitors, an unexpected pattern of response designated as hyperprogression may be observed in certain patients. This paradoxical response corresponds to an acceleration in tumor growth and a dramatic decrease of patient survival. The reported incidence rates of hyperprogressive disease are highly variable, ranging between 4 and 29%. In this review, we have performed a literature search on hyperprogressive disease, including both retrospective studies and case reports, and discuss potential predictive biomarkers as well as potential mechanisms associated with immune-checkpoint inhibitor associated hyperprogression.

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“…A number of studies have reported that the incidence of HPD ranges from 4% to 29% ( 118 – 121 ). For ovarian cancer, retrospective analysis of data from a clinical trial with a cohort of 89 patients that received ICB showed that over half of the patients (N = 46, 51.6%) experienced early treatment discontinuation (≤12 weeks after treatment initiation) due to radiographic or clinical disease progression ( 122 ). The biological basis and mechanisms underlying HPD, such as the Fc region of antibodies ( 123 ), EGFR and MDM2/MDM4 amplification ( 123 ), and senescent CD4+ T cells ( 124 ), are being clarified.…”

Section: Challenges and Future Developmentsmentioning

confidence: 99%

Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant

et al. 2020

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Ovarian cancer is the most lethal gynecologic malignancy. Surgery and chemotherapy are the primary treatments for ovarian cancer; however, patients often succumb to recurrence with chemotherapeutic resistance within several years after the initial treatment. In the past two decades, immunotherapy has rapidly developed, and has revolutionized the treatment of various types of cancer. Despite the fact that immunotherapy response rates among ovarian cancer patients remain modest, treatment with immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR)- and TCR-engineered T cells is rapidly developing. Therapeutic efficiency could be improved significantly if immunotherapy is included as an adjuvant therapy, in combination with chemotherapy, radiation therapy, and the use of anti-angiogenesis drugs, and poly ADP ribose polymerase inhibitors (PARPi). Newly developed technologies that identify therapeutic targets, predict treatment efficacy, rapidly screen potential immunotherapy drugs, provide neoadjuvant immunotherapy, and utilize nanomedicine technology provide new opportunities for the treatment of ovarian cancer, and have the potential to prolong patient survival. However, important issues that may hinder the efficacy of such approaches, including hyperprogressive disease (HPD), immunotherapy-resistance, and toxicity of the treatments, including neurotoxicity, must be taken into account and addressed for these therapies to be effective.

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Early disease progression and treatment discontinuation in patients with advanced ovarian cancer receiving immune checkpoint blockade

Cited by 39 publications

References 38 publications

Comparison of Mismatch Repair Status Between Primary and Matched Metastatic Sites in Patients With Colorectal Cancer

Comparison of Mismatch Repair Status Between Primary and Matched Metastatic Sites in Patients With Colorectal Cancer

How Can Immune Checkpoint Inhibitors Cause Hyperprogression in Solid Tumors?

Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant

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