Tracking the tail

Abstract

Immune-checkpoint inhibitors have deeply changed the therapeutic landscape of advanced non-small cell lung cancer without actionable genomic alterations. Immune-checkpoint inhibitors have become standard front-line therapy, especially among patients with tumours expressing high levels of programmed death ligand-1; yet, many patients do not respond to therapy. This has led to the adoption of front-line combination therapies, administering programmed death-1 inhibitors concomitantly either with other checkpoint inhibitors, chemotherapy or both. Today’s approved standard of care includes options with chemoimmunotherapy or dual checkpoint blockade, but each combination has only been compared to chemotherapy alone and no head-to-head trials exist. In cross-trial comparisons, combinations trials appear to show numerically superior responses to single-agent checkpoint inhibitors but the question is whether they ultimately offer a survival advantage. In this manuscript, we summarize and analyse all currently available front-line immune-checkpoint inhibitor trials in non-small cell lung cancer, whether as monotherapy or in combination with chemotherapy, second immunotherapy agents or both. Should standards of care change given the current data? While we ponder this question, we illustrate current data and conclude that the answer lies in tracking the tail of the survival curves.

Immunotherapy in lung cancer

“…This flattening of the OS Kaplan-Meier graph-the tail of the survival curve-has become a hallmark of immunotherapy benefit. 11 At the time of the initial data presentation, immunotherapy was an established modality in only a few cancers, such as melanoma and renal cell carcinoma. By demonstrating efficacy in one of the most common cancer types, NSCLC, CA209-003 increased the relevance of immunotherapy and accelerated investigation into this treatment modality.…”

“…With a minimum follow‐up of 58 months, the 5‐year OS rate was 16%. This flattening of the OS Kaplan‐Meier graph—the tail of the survival curve—has become a hallmark of immunotherapy benefit 11 . At the time of the initial data presentation, immunotherapy was an established modality in only a few cancers, such as melanoma and renal cell carcinoma.…”

Long-term benefit of immunotherapy in metastatic non-small cell lung cancer: the tale of the tail

“…In current practice, the optimal treatment selection for individual patients is still challenging due to the lack of head-to-head comparison trials. Given immunotherapy’s unique feature of durable responses, long-term follow-up and tracking the tails of these curves are crucial to better guide informed decision making discussions ( 28 ). Ultimately, the development of more precise biomarkers guiding the addition of chemotherapy or CTLA-4 inhibitors will offer tailored therapies maximizing benefit-to-risk ratios.…”