This study provides initial evidence on patient characteristics, treatment patterns, HCRU, and HCC in patients with lung cancer who received sotorasib as 2L+ treatment in real-world clinical practice in the US in the period immediately following sotorasib’s approval.

Although we excluded about 43% of the population due to lack of continuous enrollment, the use of medications commonly prescribed for SCLC, and the use of sotorasib as a first-line treatment, these exclusions were necessary to ensure the accurate estimation of LOTs to identify treatment patterns and outcomes for the eligible population.

Sotorasib was most frequently used as 2L treatment, consistent with the indication in FDA-approved prescribing information [13]. The most frequently received prior treatment was an IO in combination with CT. Age (mean 71 years; median 73 years) was substantially greater than that among patients receiving sotorasib in the CodeBreaK 100 trial (mean 53.5 years) [8] and the CodeBreaK 200 trial (median 64 years) [9]. The proportion of patients who were female also was greater than among patients receiving sotorasib in the CodeBreaK 100 and CodeBreaK 200 trials (67.1% vs. 50.0% and 36.3%, respectively).

Adherence to sotorasib, as assessed by mean PDC, was 94.9%. This compares favorably with the mean PDC of approximately 80% among patients with lung cancer receiving oral anticancer medications as assessed in 2017 using the Optum Clinformatics database [14]. Kaplan–Meier-estimated median treatment duration among patients receiving sotorasib was 4.3 months, while, among patients who received a subsequent LOT (n = 31), median TTNT was 5.8 months. These values are comparable to median PFS among patients treated with sotorasib in CodeBreaK 100 (6.3 months) [8] and CodeBreaK 200 (5.6 months) [9], as well as aligning with PFS observed in real-world studies of patients with NSCLC who received sotorasib in Italy (5.8 months) [15], Germany (4.8 months) [16], and the US (5.3 months [17] and 6.0 months [18]). However, the TTNT observed in our study was lower compared to the real-world PFS reported in Canada (8.0 months) [19].

Patients receiving sotorasib in this study averaged fewer outpatient visits, ED visits, and hospitalizations per month during sotorasib treatment than during the 180-day period prior to sotorasib treatment. Mean all-cause total healthcare costs during the sotorasib treatment period were similar to those during the 180-day period prior to initiation of sotorasib treatment, as higher prescription costs during sotorasib treatment were offset by lower medical costs.

Recent cost-effectiveness studies comparing sotorasib and docetaxel as second-line or later treatments for patients with KRAS-mutated NSCLC have been published[20, 21], based on data from the CodeBreaK 200 trial [9]. However, caution is needed when interpreting these findings, as the CodeBreaK 200 trial was not designed to robustly assess the mortality benefit—a key driver in cost-effectiveness analysis. Factors such as limited sample size, dropout rates, and treatment crossover make it difficult to draw reliable conclusions about mortality from the trial alone. Nonetheless, real-world data on sotorasib may provide a meaningful basis for evaluating its cost-effectiveness as it has demonstrated a significant mortality benefit [22].

The results of this study are generally comparable to those in other published studies examining outcomes among patients with advanced lung cancer receiving systemic anticancer therapies. A recent study, that also used the Optum database, examined patient characteristics, treatment patterns, HCRU, and HCC among patients with metastatic NSCLC receiving systemic anti-cancer therapy (SACT) treatments in the US during the period from 2020 to 2022 [23]. A total of 5310 unique NSLC patients who initiated 7010 2L+ LOTs were evaluated. Patients receiving SACT treatments were similar to the patients treated with sotorasib evaluated here in term of age (mean 72.5 vs. 71.3 years in this study), payer type (Medicare Advantage, 85.9% vs. 81.4%), and NCI-CCI (mean 2.1 vs. 2.1).). In terms of outcomes, patients using 2L+ SACT demonstrated healthcare costs similar to those treated with sotorasib (SACT: $27,105 PPPM, sotorasib: $23,063 PPPM). Another recently published study by Zhang et al. used data from the HealthCore Integrated Research Database to assess HCRU and HCC in patients with advanced NSCLC in the US over the period from 2010–2018 [24]. Compared with patients receiving sotorasib in the study reported here, patients in the study by Zhang et al. were younger (mean age 61.8 years), less likely to be female (47.7%), and less likely to be enrolled in Medicare Advantage plans (14.5%). Unlike this study, which focused on patients initiating 2L+ therapy, Zhang et al. reported results over the entire follow-up period (including 1L). For 2018, the last period for which results were reported and the most proximal to the evaluation period for this study, mean total HCC over the entire follow-up period were $24,660 PPPM (2018 US$), which is similar to that for patients receiving sotorasib as 2L+ therapy in this study ($23,063 PPPM in 2022 US$). As in the study of SACT treatments in the Optum database described above [23], in the study by Zhang et al. [24], the majority of HCC during the follow-up period were for outpatient care.

Lin et al. also used data from the Optum database to examine HCRU and HCC in 112 adult patients with advanced NSCLC who received 2L treatment with anaplastic lymphoma kinase (ALK) inhibitors between 2011 and 2017 [25]. Compared to patients treated with sotorasib in this study, patients receiving ALK inhibitors in the study by Lin et al. were younger (mean age 59.5 years), less likely to be female (51.8%), and had fewer comorbidities (75.9% had CCI ≤ 1). However, mean total HCC during 1 year of 2L ALK inhibitor therapy ($23,984 PPPM in 2017 US$) were comparable to HCC reported in patients treated with sotorasib receiving 2L+ therapy in this study.

This study is subject to limitations. The accuracy of coding of diagnoses and procedures on claims may be limited due to clerical error, and codes that describe clinical conditions or procedures may not be sufficiently detailed to identify patients and variables of interest [26]. In addition, the Optum database is limited to patients who are commercially insured or covered by Medicare advantage plans, and does not include patients in Medicare fee-for-service or Medicaid plans, and therefore may not be generalizable to all patients receiving sotorasib for NSCLC in the US. There is no International Classification of Diseases 10th Edition (ICD10) code that is specific to NSCLC, and patients were identified for this study based on a diagnosis for lung cancer, with those patients who received regimens typically used for SCLC excluded. This general approach has been validated against electronic medical record data [27]. It also was not possible to identify patients with the KRAS G12C mutation in the study databases; however, sotorasib use was determined to be a proxy for KRAS G12C status. Accordingly, identifying a control group that might be used for comparisons with patients receiving sotorasib was infeasible. LOTs were derived from claims using an adaptation of a published algorithm [11] that has not been validated against other sources (e.g., clinicians or medical records). MPR, PDC, and treatment duration were estimated based on prescriptions filled which may not reflect medications taken. HCC were based on standardized price estimates and may not reflect actual reimbursed costs. HCC and HCRU in the pre-sotorasib period may include time off NSCLC treatment and hence may not be exactly comparable to those observed during the sotorasib treatment period. Lastly, the study was conducted using data for the period immediately following the introduction of sotorasib in the US, so the sample size was therefore relatively small and the precision of estimates derived therefrom is limited. These limitations notwithstanding, the results of this study are important, as they suggest that patients who receive sotorasib as 2L+ therapy for NSCLC in real-world clinical practice have adherence to treatment that is high relative to that for other oral anticancer therapies for lung cancer.