Response assessment in metastatic melanoma treated with ipilimumab and bevacizumab: CT tumor size and density as markers for response and outcome

Abstract

Background: Investigate the tumor diameter and density changes in advanced melanoma patients treated with ipilimumab plus bevacizumab, compare response rates based on different response criteria, and study association between these measures and survival. Methods: Twenty-one advanced melanoma patients with 59 measurable lesions treated in a phase 1 trial of ipilimumab plus bevacizumab were retrospectively studied. Tumor diameter and density were measured on baseline and first follow-up CT. Responses were assigned using RECIST, MASS and Choi criteria. Diameter and density measures and responses by these criteria were studied for the association with survival. Results: Twenty-three (39%) lesions and 7 (33%) patients met the Choi density criteria for response (≥15% density decrease) at the first follow-up. The response rates were 14% (3/21, 95% CI: 3-36%) by RECIST and MASS, and 52% (11/21, 95% CI: 30-74%) by Choi criteria, when both size and density criteria were used. Larger baseline tumor diameter was significantly associated with shorter progression-free survival (PFS) and overall survival (OS) (log-rank p = 0.001 and 0.003; respectively). Diameter or density changes, or responses by RECIST, MASS or Choi criteria at the first follow-up, were not associated with PFS or OS. Conclusion: Tumor density decrease meeting Choi criteria was noted in one-third of advanced melanoma patients at the first follow-up scan during ipilimumab plus bevacizumab therapy. While larger baseline tumor diameter was strongly associated with shorter survival, changes of diameter or density, or responses by three criteria did not predict survival. The role of density changes in evaluating response during ipilimumab and bevacizumab therapy for advanced melanoma remains to be further established.

Patterns of distant metastases in 215 Merkel cell carcinoma patients: Implications for prognosis and surveillance

“…While tumor volume is initially reduced by chemotherapy in over half of patients, responses are not durable and progression typically occurs within 3 months of starting chemotherapy . Conversely, multiple trials of immune checkpoint inhibitors in skin cancers have proven to be effective and there is evidence that they are most effective when disease burden is small . This highlights the importance of using MCC‐specific metastatic patterns to detect disease spread early and provide rescue therapies before patients developed more extensive disease.…”

“…13,23 Conversely, multiple trials of immune checkpoint inhibitors in skin cancers have proven to be effective 15,20,24,25 and there is evidence that they are most effective when disease burden is small. 26 This highlights the importance of using MCCspecific metastatic patterns to detect disease spread early and provide rescue therapies before patients developed more extensive disease. In our cohort, the median time to first recurrence was less than a year, suggesting more frequent surveillance during this period could detect metastases earlier and improve the rate and/or duration of responses to immunotherapy.…”

Targeted Therapies: Immunologic Effects and Potential Applications Outside of Cancer

“…In support of this notion, higher pretreatment VEGF serum levels are associated with shorter overall survival times in melanoma patients treated with the immune checkpoint inhibitor ipilimumab, a mAb that blocks cytotoxic T lymphocyte antigen 4 (CTLA4) . Moreover, regimens combining ipilimumab (anti‐CTLA4) and bevacizumab (anti‐VEGF) are being evaluated in patients with melanoma and glioblastoma . These studies have demonstrated that the combination of bevacizumab (anti‐VEGF) and ipilimumab (anti‐CTLA4) can be safely administered with predictable and manageable toxicity.…”

“…25 Moreover, regimens combining ipilimumab (anti-CTLA4) and bevacizumab (anti-VEGF) are being evaluated in patients with melanoma and glioblastoma. [26][27][28][29] These studies have demonstrated that the combination of bevacizumab (anti-VEGF) and ipilimumab (anti-CTLA4) can be safely administered with predictable and manageable toxicity. Moreover, these studies illustrate that the combination of bevacizumab and ipilimumab can augment endothelial cell activation, lymphocyte infiltration into tumors, cytokine and chemokine expression, and antimelanoma humoral responses.…”

Investigation of the effects of angiogenesis on tumor growth using a mathematical model

“…Using observe the results of using AAT [6][7][8]. The prediction of its antitumor effectiveness beforehand using math ematical simulation could be attempted.…”