Reviews & Analysis

In 2018, the SOLO1 trial set a new standard of care with maintenance olaparib substantially extending progression-free survival (PFS) in women with newly-diagnosed BRCA1/2-mutated advanced-stage ovarian cancer. Herein, we summarize trials of first-line poly(ADP-ribose) polymerase (PARP) inhibition beyond BRCA1/2 mutations, including combination strategies, and discuss the optimum use of PARP inhibition in advanced-stage ovarian cancer.

An immunosuppressive tumour microenvironment is one of the main reasons why patients with solid tumours fail to respond to immune-checkpoint inhibition. In this Perspective, the authors describe the potential of nanomedicines to normalize the tumour microenvironment, thus overcoming this immunosuppressive barrier and enabling greater numbers of patients to respond to immune-checkpoint inhibition.

Regulatory approval of new cancer medicines can have important consequence for patients with advanced-stage and/or rare cancers who have exhausted all standard-of-care therapies. However, evidence that new medicines are safe and effective can also take time to accrue, and approval with a lack of evidence may cause unnecessary harm to patients. In this Viewpoint, we asked two leading oncologists involved in clinical drug development, an expert in regulatory science and prescription drug policy, and a prominent patient advocate, to provide their opinions on the current approach to cancer drug approvals.

Liu et al. report data from the largest sequencing analysis of tumour material from patients with metastatic melanoma receiving immune-checkpoint inhibitors. These data confirm the correlations between baseline immune infiltrate and treatment response, but also demonstrate inconsistent associations of tumour mutational burden, specific gene mutations and previously described gene expression patterns with clinical outcomes.

Interval invasive breast cancers diagnosed after a normal mammogram but before the next screening examination have a different tumour biology from that of screen-detected breast cancers, and thus are not detected on mammography. Understanding the genetics and biology of interval invasive cancers could inform better approaches to detection.

The CHECKMATE-227 trial of nivolumab and ipilimumab presents a potential new frontline chemotherapy-sparing treatment option for patients with PD-L1-positive non-small-cell lung cancer and perhaps, in the future, also for those with PD-L1-negative disease. Indeed, the true predictive value of PD-L1 as well as tumour mutational burden remains to be determined, as neither biomarker segregates clearly with responsiveness.