Adaptive Dosing of Nivolumab + Ipilimumab Immunotherapy Based Upon Early, Interim Radiographic Assessment in Advanced Melanoma (The ADAPT-IT Study)

PURPOSE Nivolumab + ipilimumab (nivo + ipi) is highly efficacious but has high toxicity. Standard treatment in advanced melanoma is four doses of nivo + ipi followed by nivo alone. Whether four doses of nivo + ipi are needed is unclear. METHODS The Adaptively Dosed ImmunoTherapy Trial (ADAPT-IT) study ( NCT03122522 ) is a multicenter, single-arm phase II clinical trial. Patients received two doses of nivo (1 mg/kg) + ipi (3 mg/kg) followed by a computed tomography scan at week 6. Patients without new lesions or index lesion tumor growth of > 4% had protocol-defined early favorable antitumor effect (FATE) and ceased nivo + ipi, transitioning to nivo monotherapy. Patients without FATE at week 6 received the standard third and fourth doses of nivo + ipi followed by nivo monotherapy. The primary end point was response rate by RECIST 1.1 at week 12. Secondary end points included additional efficacy assessments and safety. RESULTS Sixty patients were enrolled; 41 patients (68%) had FATE at week 6 and met criteria for stopping nivo + ipi. Best overall response rates by RECIST at week 12 or any time afterward were 48% (95% CI, 35 to 62) and 58% (95% CI, 45 to 71), respectively. With a median follow-up of 25 months, the estimated 18-month progression-free survival and overall survival are 52% and 80%, respectively. Fifty seven percent of patients had grade 3-5 treatment-related toxicity. CONCLUSION The efficacy and toxicity of standard four dose nivo + ipi induction therapy in melanoma is likely driven by the first two doses. An interim computed tomography scan after two doses guided cessation of combination dosing and identified almost all responders. Longer follow-up and further study are needed to fully understand the implications of a shortened induction course of nivo + ipi.

Moving beyond conventional stratified analysis to assess the treatment effect in a comparative oncology study

In a comparative oncology study with progression-free or overall survival as the endpoint, the primary or key secondary analysis is routinely stratified by patients’ baseline characteristics when evaluating the treatment difference. The validity of a conventional strategy such as a stratified HR analysis depends on stringent model assumptions that are unlikely to be met in practice, especially in immunotherapy studies. Thus, the resulting summary is generally neither valid nor interpretable. This article discusses issues with conventional stratified analyses and presents alternatives using data from KEYNOTE-189, a recent immunotherapy trial for treating patients with metastatic, non-squamous, non-small-cell lung cancer.

EPCT-20. TECHNICAL FEASIBILITY SODIUM (23NA) MRI OF PEDIATRIC GLIOMAS

Pediatric glioma response to novel targeted therapy can be heterogeneous on conventional proton (1H) MRI. Sodium concentration, as measured with 23Na MRI in adult brain tumors can provide complementary assessment of tumor proliferation to conventional MRI. However, 23Na MRI pediatric brain tumor studies are lacking. Determine the technical feasibility of performing sodium23Na MRI on pediatric glioma patients. Prospective study of an immunotherapy trial for newly diagnosed and recurrent gliomas (high-grade gliomas, low-grade gliomas, brainstem gliomas) in which participants were imaged with 23Na MRI at 3.0 Tesla. The participants (n=26, 14 males) with median age of 11 years (range = 4–23 years of age) were prospectively evaluated with sodium. 23Na MRI is technically feasible in the pediatric population and can distinguish different types of pediatric gliomas at baseline.

Case of metastatic kaposi sarcoma successfully treated with anti-PD-1 immunotherapy

Introduction Kaposi sarcoma (KS) is an angioproliferative malignancy associated with HHV-8. It is mostly observed in patients affected by HIV and/or chronic immunosuppression, while classic KS without underlying immunosuppression are relatively rare. Systemic chemotherapy is used for advanced diseases, although there is no consensus in treatment algorithms. With the demonstration of PD-1 expression in KS, immune-checkpoint-inhibitors (ICI) emerged as possible treatment options. Notwithstanding, the data of ICIs is limited to case reports/series. Herein, we present a case of advanced classic KS, which has been treated successfully with nivolumab. Case report 82-year-old male patient was investigated for erythematous lesions on thigh. Punch biopsy lead to KS diagnosis. Abdominal CT showed lymphadenopathies in the inguinal region. After radiotherapy follow-up, patient had shown vertebral & gastric metastases. Because of the PSA elevation patient was diagnosed with prostatic adenocarcinoma. Metastases were investigated for origin. The lesions showed no uptake in Ga-68 PET-CT, therefore accepted as KS metastases. Patient rejected chemotherapy options and consented to immunotherapy trial. Management and outcome: Nivolumab was initiated 3 mg/kg bi-weekly with 12-dose protocol. After nivolumab patient wellbeing is improved and control endoscopy shown no metastases. With these findings patient has been assessed as complete response. Discussion ICI on KS is still a blurred option to be included in standard regimens; but progressive understanding of PD-1 expression and its role in disease progression may be a milestone for further treatment algorithms on KS. Besides good efficacy, tolerability of ICIs could be helpful patients with comorbidities precluding the use of chemotherapy.