Subcutaneous Atezolizumab Is Equivalent to Intravenous Formulation in NSCLC

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As an alternative to intravenous (IV), atezolizumab (Tecentriq) can be administered subcutaneously and it is a preferred method of delivery by patients with non–small cell lung cancer (NSCLC), according to findings from the phase 2 IMscin002 trial (NCT03735121). These results were presented at the European Lung Cancer Congress 2024 in Prague, Czech Republic.¹

In the crossover study findings, 71% of patients reported that they were satisfied with subcutaneous (SC) administration vs 21% for the IV delivery method. Furthermore, during the continuation phase, the SC method was the main route of administration chosen by patients (79%), with most patients (86%) reporting that they were “very satisfied or satisfied” with SC atezolizumab.

In addition, 8.1% of patients (10 of 123) had no preference between the SC and IV forms. The primary reasons for preferring the SC option included less time in the clinic (64.4%), administration was more comfortable (46.0%), and treatment was less emotionally distressing (29.9%). “SC usage of atezolizumab gave relevant advantage for the patients and the institutions, and these results support all the previous findings that SC atezolizumab is equivalent to IV use,” lead study author Federico Cappuzzo, MD, director of medical oncology at Azienda Unità Sanitaria Locale della Romagna -Ravenna in Italy, said in a presentation of the data.

In January 2024, the European Commission granted marketing authorization for SC atezolizumab coformulated with Enhanze, a recombinant human hyaluronidase enzyme rHuPH20, for all approved indications of IV atezolizumab.² That regulatory decision was supported by data from the phase 1b/3 IMscin001 trial (NCT03735121).

IMscin002 was an open-label crossover study that enrolled patients 18 years or older with EGFR/ALK wild-type NSCLC who had an ECOG performance status of 0 or 1. Patients were allowed to have resected stage II to IIIB disease that was PD-L1 positive (≥ 1%) and previously treated with adjuvant chemotherapy or to have stage IV NSCLC that was PD-L1 high (≥ 50%) and naive to chemotherapy.¹

All patients were randomly assigned 1:1 to receive 3 cycles of SC atezolizumab at 1875 mg once every 3 weeks for 3 cycles followed by IV atezolizumab at 1200 mg once every 3 weeks for 3 cycles or the inverse sequence for 3 cycles each. During the continuation period following 6 cycles of treatment, patients were permitted to choose between the SC and IV formulations. Patients were stratified by disease stage (II vs III vs IV) and type of surgery (no surgery vs pneumonectomy vs any other surgery).

The study’s primary end point was the proportion of patients who preferred SC atezolizumab vs the IV formulation at day 1 of cycle 6 during the crossover period, as assessed by a patient preference questionnaire. Secondary end points included patient-reported satisfaction, patient’s choice of treatment during the continuation period, and safety.

Among all patients (n = 179), the median age was 67 years (range, 39-91). The majority of patients were men (67%) and White (83%), had an ECOG performance status of 1 (55%), were former smokers (64%), had not received prior systemic therapy (60%), had stage IV disease at the time of enrollment (65%), had nonsquamous histology (63%), and had not undergone surgery (58%).

Additional data showed that 85.8% of patients were very satisfied or satisfied with SC atezolizumab compared with 75.2% of patients for the IV formulation. For SC atezolizumab, patients (n = 127) were very satisfied (40.9%), satisfied (44.9%), neither satisfied nor dissatisfied (11.0%), dissatisf ied (2.4%), or very dissatisfied (0.8%). For IV atezolizumab, patients (n = 123) were very satisfied (26.3%), satisfied (48.9%), neither satisfied nor dissatisfied (21.1%), dissatisfied (1.5%), or very dissatisfied (2.3%). Cappuzzo also noted that SC atezolizumab does not need to be prepared in sterile conditions and can be prepared in the ward, and he explained that nurses in the ward could prepare the agent 3 times faster than pharmacists in the pharmacy.

Safety data were consistent with the known profile of atezolizumab, with no new safety concerns identified. Furthermore, switching between the SC and IV formulations of atezolizumab was well tolerated, irrespective of sequence. Notably, rates of infusion-site reactions or infusion-site reaction adverse effects (AEs) did not increase when switching between the SC and IV formulations, irrespective of the first treatment used.

During crossover, in patients who started with SC atezolizumab in cycles 1 to 3 (n = 86) and received IV atezolizumab in cycles 4 to 6 (n = 71), the rates of any-grade AEs were 54.7% with the SC formulation and 53.5% with the IV formulation. The rates of treatment-related AEs (TRAEs) were 36% and 31%, respectively. One patient (1.2%) experienced a TRAE with SC atezolizumab that proved fatal.

The rates of serious AEs were 12.8% and 5.6% for SC atezolizumab in cycles 1 to 3 and IV atezolizumab in cycles 4 to 6, respectively. Serious TRAEs occurred at rates of 4.7% and 2.8%, respectively. For SC atezolizumab, the rates of grade 3/4 AEs and grade 3/4 TRAEs were 15.1% and 5.8%, respectively; those respective rates were 9.9% and 1.4% for IV atezolizumab. The rates of AEs leading to treatment discontinuation and interruption for SC atezolizumab were 5.8% and 10.5%, respectively, vs 2.8% and 9.9% for IV atezolizumab.

In patients who received IV atezolizumab in cycles 1 to 3 (n = 89) and SC atezolizumab in cycles 4 to 6 (n = 69), the rates of any-grade AEs were 62.9% and 39.1%, respectively. The rates of TRAEs were 31.5% and 30.4%, respectively, and 1 patient each experienced a fatal TRAE with the IV formulation (1.1%) and with the SC formulation (1.4%).

The rates of serious AEs were 12.4% and 2.9% for IV atezolizumab in cycles 1 to 3 and SC atezolizumab in cycles 4 to 6, respectively. Serious TRAEs occurred at rates of 4.5% and 2.9%, respectively. For IV atezolizumab, the rates of grade 3/4 AEs and grade 3/4 TRAEs were 16.9% and 6.7%, respectively; those rates were both 0% for SC atezolizumab. The rates of AEs leading to treatment discontinuation and interruption for IV atezolizumab were both 7.9% vs 2.9% for both with SC atezolizumab.”

REFERENCES :

1. Cappuzzo F, Zvirbule Z, Korbenfeld EP, et al. Primary results from IMscin002: a study to evaluate patient (pt)- and healthcare professional (HCP)-reported preferences for atezolizumab (atezo) subcutaneous (SC) vs intravenous (IV) for the treatment of NSCLC. Ann Oncol. 2024;9(suppl 3): 102706. doi:10.1016/esmoop/esmoop102571

2. Halozyme announces Roche receives European Commission approval of Tecentriq SC with Enhanze representing the EU’s first subcutaneous PD-(L)1 cancer immunotherapy for multiple cancer types. News release. Halozyme Therapeutics. January 16, 2024. Accessed March 22, 2024. https://tinyurl.com/yfbpfmmd