A randomized controlled comparison of pembrolizumab and chemotherapy in patients with ipilimumab-refractory melanoma

Dummer, Reinhard; Daud, Adil; Puzanov, Igor; Hamid, Omid; Schadendorf, Dirk; Robert, Caroline; Schachter, Jacob; Pavlick, Anna C.; González, René; Hodi, F. Stephen; Cranmer, Lee D.; Blank, Christian U.; O’Day, Steven; Ascierto, Paolo A.; Salama, April K.S.; Li, Nicole Xiaoyun; Zhou, Wei; Lis, Joy; Ebbinghaus, Scot; Kang, Peter; Ribas, Antoni

doi:10.1186/1479-5876-13-s1-o5

Cited by 29 publications

(24 citation statements)

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“…These are the first major developments since dacarbazine (DTIC) was approved by the US Food and Drug Administration (FDA) in 1976. DTIC has demonstrated very low response rates (< 10%) and no survival benefit [9][10][11], while the new generation of immunotherapies such as CTLA-4 and PD-1 inhibitors as well as targeted therapies such as BRAF-and MEK-inhibitors have each demonstrated increased treatment benefits compared to traditional therapies [7,[12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Patient-reported treatment-related symptom burden for patients with advanced melanoma in Canada

Cheung

White

Bayliss

et al. 2018

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Background Little is known on the impact of emerging treatments for advanced melanoma (stages III and IV) on patients' functioning and well-being. The objective of this study was to describe the patient-reported treatment-related symptom (TRS) burden in advanced melanoma. Method Twenty-nine in-depth, qualitative interviews were conducted among adult patients with advanced melanoma in Canada using a semi-structured interview method. Interviews were transcribed verbatim, and key concepts were identified using a grounded theory analytic approach. Results The 29 patients reported 13 unique treatment journeys involving the following drug therapy categories: cytotoxic chemotherapies, CTLA-4 inhibitors, BRAF or MEK inhibitors, and PD-1 inhibitors. Patients typically underwent multiple treatment episodes over time. Common TRSs included nausea, fatigue, diarrhea or constipation, and skin rashes. Patients described these as impacting their physical functioning, ability to perform activities of daily living, social functioning, and overall quality of life. Conclusion Our findings provide a description of the patient's experience with treatment for advanced melanoma. Our sample included patients typically diagnosed in mid-life, facing an urgent sequence of medical procedures and a pharmacological treatment journey that was burdensome. There is a need for less toxic and more efficacious treatments earlier in the patient journey to alleviate the impact of advanced melanoma treatment on patients' health-related quality of life.

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Section: Introductionmentioning

confidence: 99%

Patient-reported treatment-related symptom burden for patients with advanced melanoma in Canada

Cheung

White

Bayliss

et al. 2018

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“…It also allows for the targeting of these molecules in succession or in combination. A new pathway may be targeted after the efficacy of an earlier immunotherapy is exhausted as evidenced by the success of PD-1 targeting mAbs in ipilimumab-refractory tumors indicating that tumors may recruit additional pathways when one is blocked, or several pathways may be in fact be recruited simultaneously by tumor cells [24,25,31]. Efficacy of ipilimumab in combination with nivolumab also illustrates that tumors may recruit more than one inhibitory pathway at the same time [143].…”

Section: Conclusion and Future Perspectivementioning

confidence: 99%

“…Combination of immune checkpoint inhibitors have also been studied with traditional immunotherapies or targeted therapies such as rituximab and cetuximab where they show efficacy and tolerability [105,106,146]. With evidence pointing to better outcomes in second line setting or even first line setting of immunotherapies, cancer immunotherapy will play a vital role in the future of oncology [24,31,147]. • Provides a conceptual overview of cancer where tumor immunology fits in the overall spectrum on tumor genesis.…”

Section: Conclusion and Future Perspectivementioning

confidence: 99%

“…Several mAbs targeting PD-1 have progressed through clinical trials. The first FDA approved mAb was pembrolizumab (Keytruda ® ), also known as lambrolizumab after showing response rates in melanoma patients who have progressed after first line therapy including immunotherapy with ipilimumab (KEYNOTE-001 trial) or in comparison to investigator-choice chemotherapy (KEYNOTE-002) [24,25]. The second PD-1 targeting mAb to receive FDA approval was nivolumab (Opdivo ® ).…”

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Emerging Targets in Cancer Immunotherapy: Beyond CTLA-4 and PD-1

et al. 2015

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Manipulation of co-stimulatory or co-inhibitory checkpoint proteins allows for the reversal of tumor-induced T-cell anergy observed in cancer. The field has gained credence given success with CTLA-4 and PD-1 inhibitors. These molecules include immunoglobulin family members and the B7 subfamily as well as the TNF receptor family members. PD-L1 inhibitors and LAG-3 inhibitors have progressed through clinical trials. Other B7 family members have shown promise in preclinical models. TNFR superfamily members have shown variable success in preclinical and clinical studies. As clinical investigation in tumor immunology gains momentum, the next stage becomes learning how to combine checkpoint inhibitors and agonists with each other as well as with traditional chemotherapeutic agents.

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“…Pembrolizumab represents a major step in ipilimumab-refractory melanoma therapy, significantly prolonging progression-free survival in comparison to chemotherapy. 6 The assessment of the therapeutic benefit of pembrolizumab and, in general, immunotherapeutic agents represents a major challenge, because these therapies may initially lead to tumor enlargement, before a potential disease stabilization or response takes place. 7,8 18 F-FDG PET/CT has recently shown promising results in treatment response monitoring of metastatic melanoma patients undergoing ipilimumab therapy.…”

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confidence: 99%

18F-FDG PET/CT Reveals Disease Remission in a Patient With Ipilimumab-Refractory Advanced Melanoma Treated With Pembrolizumab

Sachpekidis

Hassel

Dimitrakopoulou-Strauß

2016

Clinical Nuclear Medicine

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Pembrolizumab is an anti-programmed cell death receptor 1 (anti-PD-1) antibody, recently approved for the treatment of ipilimumab-refractory metastatic melanoma. We report on a 49-year-old patient with unresectable metastatic melanoma initially treated with 4 cycles of ipilimumab. Because of demonstration of progressive disease on PET/CT, the patient was enrolled into a clinical trial of pembrolizumab. After completion of 4 cycles of pembrolizumab, the follow-up PET/CT scans performed early after and 7 months after the end of treatment exhibited complete disease remission, reflecting the potential role of the modality in treatment response evaluation of melanoma patients receiving anti-PD-1 therapy.

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A randomized controlled comparison of pembrolizumab and chemotherapy in patients with ipilimumab-refractory melanoma

Cited by 29 publications

References 0 publications

Patient-reported treatment-related symptom burden for patients with advanced melanoma in Canada

Patient-reported treatment-related symptom burden for patients with advanced melanoma in Canada

Emerging Targets in Cancer Immunotherapy: Beyond CTLA-4 and PD-1

18F-FDG PET/CT Reveals Disease Remission in a Patient With Ipilimumab-Refractory Advanced Melanoma Treated With Pembrolizumab

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