Selected Articles from This Issue

Effective systemic treatment options are largely limited for previously treated liposarcoma and leiomyosarcoma. In this phase II study, Kim and colleagues show that eribulin–gemcitabine combination therapy demonstrated appreciable efficacy compared to monotherapy from the historic arm. Functional enrichment in the transforming growth factor-ß pathway would hold predictive value for the survival outcomes of the combination therapy, although further confirmatory investigation may be required. Eribulin–gemcitabine combination therapy could present as a future treatment option for refractory soft tissue sarcomas with liposarcoma or leiomyosarcoma histology.

Chemotherapy resistance remains a key challenge in the treatment of solid tumors. Cortisol can facilitate resistance by suppressing apoptotic pathways that cytotoxic agents utilize. Munster and colleagues studied the ability of relacorilant, a selective glucocorticoid receptor modulator, to restore chemosensitivity and enhance chemotherapy efficacy by reversing cortisol’s antiapoptotic effects. In preclinical studies, relacorilant enhanced chemotherapy efficacy. A phase I study showed durable disease control with relacorilant + nab-paclitaxel in patients with treatment-refractory solid tumors, including those with prior taxane exposure. These findings indicate that relacorilant combined with nab-paclitaxel may promote chemotherapy response. Further evaluation of this combination is ongoing.

Zhang and colleagues assessed the antitumor activity and safety of PD-1 inhibitor camrelizumab plus platinum-based chemotherapy in patients with resectable locally advanced head and neck squamous cell carcinoma (HNSCC) in the neoadjuvant setting. In this phase II single-arm clinical trial, camrelizumab, combined with neoadjuvant chemotherapy, showed a favorable safety profile without surgical delay and exhibited encouraging efficacy results, including high rates of objective response rate (96.7%) and pathologic response. The pathologic complete response rate (37.0%) or major pathologic response rate (74.1%), was higher than that previously reported with PD-1 inhibitor alone (0%-6.7%) or in combination with the CTLA4 antibody. These results provide initial evidence for the safety and efficacy of neoadjuvant chemoimmunotherapy for the treatment of locally advanced HNSCC.

Patients with KRAS-mutant non–small cell lung cancer with brain metastases have a poor prognosis. Here, Sabari and colleagues report data supporting central nervous system penetration and anti-tumor activity of adagrasib, an oral small molecule KRASG12C inhibitor, in preclinical models and in patients harboring brain metastases. These data form the rationale for further clinical development of adagrasib in this patient population. Patients with active, untreated brain metastases are currently being enrolled in a Phase Ib cohort of the KRYSTAL-1 trial.