Abstract
Although PD-1 antibodies (PD1 Ab) are the standard of care for advanced non-small-cell lung cancer (ansclc), most patients will progress. We compared survival outcomes for patients with ansclc who received systemic therapy (st) after progression and for those who did not. Additionally, clinical characteristics that predicted receipt of st after PD1 Ab failure were evaluated. All patients with ansclc in British Columbia initiated on nivolumab or pembrolizumab between June 2015 and November 2017, with subsequent progression, were identified. Eligibility criteria for additional st included an Eastern Cooperative Oncology Group (ecog) performance status (ps) of 3 or less and survival for more than 30 days from the last PD1 Ab treatment. Post-progression survival (pps) was assessed by landmark analysis. Baseline characteristics associated with pps were identified by multivariable analysis. Of 94 patients meeting the eligibility criteria, 33 received st after progression. In 75.6%, a PD1 Ab was received as first- or second-line treatment. The most common sts were erlotinib (36.4%) and docetaxel (27.3%). No statistically significant difference in median pps was observed between patients who did and did not receive st within 30 days of their last PD1 Ab treatment (6.9 months vs. 3.6 months, log-rank p = 0.15.) In multivariable analysis, factors associated with increased pps included an ecog ps of 0 or 1 compared with 2 or 3 [hazard ratio (hr): 0.42; 95% confidence interval (ci): 0.24 to 0.73; p = 0.002] and any response compared with no response to PD1 Ab (hr: 0.54; 95% ci: 0.33 to 0.90; p = 0.02). In this cohort, only 35.1% of patients eligible for post-PD1 Ab therapy received st. Post-progression survival was not significantly affected by receipt of post-progression therapy. Prospective trials are needed to clarify the benefit of post-PD1 Ab treatments.
Highlights
In the 20th century, the toxicity from radiation on the human body became evident through accidental exposures [1,2,3]
Later, during the 1960s in Canada, Till and McCulloch, while studying the sensitivity of mouse bone marrow cells to radiation, made some of the first observations that “stem cells” could recapitulate the blood system [10]. This knowledge was developed into the technique of marrow transplantation which could be applied to humans to eliminate marrow disease with radiation, such as acute leukemia, and salvage the irradiated bone marrow using donor marrow
In contrast to the bulk of radiation oncology which is accustomed to delivering high doses of radiation to a relatively small area in a large number of patients with solid tumors, Total body irradiation (TBI) is focused on delivering a low dose of radiation homogeneously to the entire body in a small number of patients
Summary
In the 20th century, the toxicity from radiation on the human body became evident through accidental exposures [1,2,3]. Later, during the 1960s in Canada, Till and McCulloch, while studying the sensitivity of mouse bone marrow cells to radiation, made some of the first observations that “stem cells” could recapitulate the blood system [10] This knowledge was developed into the technique of marrow transplantation which could be applied to humans to eliminate marrow disease with radiation, such as acute leukemia, and salvage the irradiated bone marrow using donor marrow. Donnall Thomas and colleagues throughout the 1970s—work for which he was award the Nobel Prize in 1990 [11,12,13,14,15,16] Throughout the decade, they observed that higher doses of radiation would prolong recovery of the bone marrow, which could be salvaged within 2 weeks at a dose of around 1000 roentgens, from opposing 60Co sources, with donor marrow and this process did not produce troublesome radiation sickness in patients. With newer chemotherapies in modern times, the number of combinations with TBI has started to flourish in an attempt to maintain the cytotoxic effects of TBI while minimizing associated toxicity [8,17,18,19,20]
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