Extended Interval Dosing With Zoledronic Acid in Metastatic SCLC and NSCLC Appears to Be a Safe and Reasonable Option


Patients with non–small cell lung cancer and small-cell lung cancer with bone metastases may benefit from extended dosing with zoledronic acid.

Extended interval dosing with zoledronic acid (Reclast) compared yielded comparable incidence and time to skeletal-related events (SREs) vs standard dosing and could be a safe and reasonable option for patients with non–small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) with bone metastases, according to the results of an article published in Annals of Pharmacotherapy.

The incidence of SRE within 1-year of treatment with zoledronic acid given every 12 weeks was 23.5% compared with 23.9% when administered every 4 weeks (95% CI, -0.184 to 0.192; P = .968). The median time to first SRE was not reached for either cohort (P = .530). Patients who received zoledronic acid every 12 weeks had a long median overall survival (OS) at 24.0 months compared with 8.97 months in the 4-week cohort (P = .022).

“Overall rate of SRE in this analysis is similar to results in previous studies—ranging from

30% to 40%—of patients with lung cancer receiving zoledronic acid. Numerical differences between incidence of SRE reported in this analysis and in the published literature may be a result of drastic improvements in treatment of lung cancer demonstrated in the past decade,” the study’s investigators wrote.

Investigators enrolled 80 patients, 34 of whom received zoledronic acid every 12 weeks and 46 who received it every 4 weeks. Patients with NSCLC comprised 96.3% (n = 77) of the study population. Investigators did not find a difference in median number of bone metastases at baseline (P = .944), history of SRE (P = .555), history of oral bisphosphate (P = .388), or concomitant calcium (P = .159), vitamin D, (P = .921), or oral corticosteroid use (P = .402).

Additionally, investigators did not note any difference in the line of systemic therapy when zoledronic acid was started; the median was 1 (range, 1-4; P = .154). The majority of patients received zoledronic acid at the time of first systemic therapy in both the 12-week cohort (64.7%) and the 4-week cohort (78.3%; P = .180).

In the 12-week group, 41% (n = 14) of patients were EGFR positive compared with 10.9% (n = 5) of those in the 4-week group (P = .002). In total, 5.9% of patients in the 12-week group had ALK fusions vs 2.2% of patients in the 4-week group (P = .572). Additionally, the differences in ROS1 fusions (2.9% vs 0%; P = .425), and PD-L1 expression greater than 50% (11.8% vs 4.3%; P = .393) between the 2 arms, respectively, were not considered significant. Due to of this, more patients in the 12-week group (38.2%) were treated with an EGFR inhibitor vs the 4-week group (17.4%; P = .036). Patients in the 4-week group were more likely to receive traditional chemotherapy (80.4%) compared with the 12-week group (50%; P = .004), as well as bevacizumab (Avastin; 15.2% vs 0%; P = .019).

A similar number of patients in the 12-week group and the 4-week group were treated with immunotherapy (26.5% vs 26.1%; P = .969). The baseline renal function and median scores were the also similar.

The time to first SRE did not differ significantly between groups with the 12-week group (10.6 months) and the 4-week group (9.9 months). Additionally, investigators did not identify a significant difference in the proportion of patients who experienced a second SRE (P = .572).

Zoledronic acid dosing interval was associated with a longer OS, as demonstrated by the COX proportional-hazards model (HR, 0.528; 95% CI, 0.300-0.928; P = .026). Notably, treatment with targeted therapy (HR, 0.851; 95% CI, 0.487-1.486; P = .570) and immunotherapy (HR, 1.032; 95% CI, 0.526-2.027; P = .926) did not have a significant impact on survival.

Investigators stated that there was little difference between the median number of doses in the 12- and 4-week groups (3.5 months and 4 months, respectively; P = .161) or the total cumulative acid dose received (12.65 mg and 16.0 mg, respectively; P = .138). In terms of safety, 2 patients—1 from each cohort—experienced grade 2 kidney dysfunction (P = 1.00). No patients in either group experienced grade 3 or 4 kidney dysfunction, although grade 3 hypocalcemia occurred in 1 patient in the 4-week group. There were no patients in either group who experienced osteonecrosis of the jaw.


Tam AH, Schepers AJ, Qin A, Nachar VR. Impact of extended-interval versus standard dosing of zoledronic acid on skeletal events in non-small-cell lung cancer and small-cell lung cancer patients with bone metastases. Ann Pharmacother. 2021;55(6):697-704. doi:10.1177/1060028020967629

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