Abstract
For more than a decade, there has been no improvement in outcomes for patients with unresectable locally advanced (la) non-small-cell lung cancer (nsclc). The standard treatment in that setting is definitive concurrent chemotherapy and radiation (ccrt). Although the intent of treatment is curative, most patients rapidly progress, and their prognosis is poor, with a 5-year overall survival (os) rate in the 15%-25% range. Those patients therefore represent a critical unmet need, warranting expedited approval of, and access to, new treatments that can improve outcomes. The pacific trial, which evaluated durvalumab consolidation therapy after ccrt in unresectable la nsclc, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (pfs) and a significant improvement in os. Durvalumab thus fills a critical unmet need in the setting of unresectable la nsclc and provides a new option for patients treated with curative intent. Here, we review the treatment of unresectable la nsclc, with a focus on the effect of the clinical data for durvalumab.
Highlights
Lung cancer remains the leading cause of cancer-related death in Canada, carrying a morbidity rate higher than the rate for the other three major-incidence cancer types combined[1]
Given the high risk of metastasis and a short pfs after ccrt, one strategy aimed at improving outcomes is consolidation therapy, defined as treatment administered after the end of a defined number of chemotherapy cycles with or without rt, in a patient whose tumour has been controlled[16]
A single-arm phase ii study of pembrolizumab given as consolidation after ccrt enrolled 92 patients and demonstrated a pfs of 17 months, similar to that seen with durvalumab, with a rate of grades 3–5 pneumonitis of 6.5%38, providing further support for the effectiveness and safety of anti–PD-1/PD-L1 antibodies in improving outcomes for patients with unresectable la nsclc
Summary
Lung cancer remains the leading cause of cancer-related death in Canada, carrying a morbidity rate higher than the rate for the other three major-incidence cancer types (breast, colon, and prostate) combined[1]. Given the high risk of metastasis and a short pfs after ccrt, one strategy aimed at improving outcomes is consolidation therapy, defined as treatment administered after the end of a defined number of chemotherapy cycles with or without rt, in a patient whose tumour has been controlled[16]. To date, no phase iii studies of consolidation with chemotherapy, targeted therapy, or vaccines have demonstrated a pfs or os benefit in patients with unresectable la nsclc (Table i).
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