Selected Articles from This Issue

Abstract

Carboplatin is commonly used for treating many solid cancers, but many patients develop resistance, necessitating combination treatment. Preclinical studies have shown that the combination of ceralasertib, an ATR inhibitor, and carboplatin may hold clinical promise. Here, Yap and colleagues report the results of a multicenter phase I study of ceralasertib plus carboplatin in patients with advanced solid cancers. This combination was well tolerated and showed potential clinical activity, with 18 of 34 patients showing stable disease. Two patients with absent or low ATM or SLFN11 protein expression achieved confirmed partial responses. Further clinical study is necessary to validate the clinical utility of this combination.The randomized phase III coBRIM study (NCT01689519) demonstrated that the addition of cobimetinib to vemurafenib improved progression-free survival (PFS) and overall survival (OS) in patients with previously untreated BRAFV600-positive advanced melanoma. Ascierto and colleagues report long-term follow-up of this study. Over at least 5 years of follow-up. results of PFS and OS benefits remain for cobimetinib plus vemurafenib compared with vemurafenib monotherapy. Normal baseline lactate dehydrogenase levels, low tumor burden, and a complete response were associated with extended OS and PFS. These results confirm the clinical utility of this combination.The combined targeting of PD-1 and CTLA-4 has provided benefit to patients with advanced melanoma, but toxicity has been a challenge, primarily due to ipilimumab. To further tailor dosing of ipilimumab, Long and colleagues conducted a clinical trial assessing standard-dose pembrolizumab plus alternative ipilimumab dosing regimens in patients with advanced melanoma. All patients received pembrolizumab at 200 mg every 3 weeks plus ipilimumab at either 50 mg (PEM200+IPI50) every 6 weeks or 100 mg (PEM200+IPI100) every 12 weeks. The PEM200+IPI50 regimen reduced both treatment-related adverse events and immune-mediated adverse events compared to PEM200+IPI100. The ORR was 55% in PEM200+IPI50 and 61% in PEM200+IPI100. Based on these data, further clinical trials of PD-1 inhibitors with alternative ipilimumab dosing are warranted.Adoptive cell transfer of tumor-infiltrating lymphocytes (ACT-TIL) can mediate durable complete responses in patients with metastatic melanoma after a single treatment. To evaluate ACT-TIL in the era of checkpoint inhibition and targeted molecular therapy, Seitter and colleagues analyzed a cohort of 226 patients treated as part of ACT-TIL clinical trials. Patients who had received PD-1 blockade or MAPK inhibitors prior to ACT-TIL demonstrated a lower objective response rate and shorter melanoma-specific survival after ACT-TIL than patients who were naïve to those treatments. These data suggest a potential role for ACT-TIL as a front-line therapy for eligible patients.