Prior Immunotherapy or Osimertinib Negatively Impacts Outcomes With Subsequent Atezolizumab in NSCLC

Previous exposure to immune checkpoint inhibitors or osimertinib (Tagrisso) has been linked with poor outcomes in patients with non–small cell lung cancer (NSCLC) who were receiving a subsequent atezolizumab (Tecentriq)-containing regimen, according to real-world observational data from a retrospective study presented during the 2021 European Lung Cancer Conference.¹

Among the 128 patients who received atezolizumab-containing regimens, the response rate achieved was 10.2%, the median progression-free survival (PFS) was 3.5 months (95% CI, 2.9-4.1), and the median overall survival (OS) was 10.7 months (95% CI, 9.4-12.0).

Patients who had previously received immune checkpoint inhibitors before an atezolizumab-containing regimen (n = 13) experienced poorer outcomes with atezolizumab than those who did not receive prior immunotherapy. The median progression-free survival (PFS) in this subgroup was 2.4 months vs 3.5 months in those without prior immunotherapy (P = .009), while the median overall survival (OS) was 6.3 months vs 11.0 months, respectively (P = .030).

Patients who had prior exposure to osimertinib (n = 9) also experienced poorer atezolizumab treatment outcomes than those who did not previously receive the EGFR TKI. The median PFS in those with prior osimertinib treatment was 2.8 months vs 4.8 months in those without prior osimertinib (P = .010), while the median OS was 5.4 months vs 12.0 months, respectively (P <.001).

In recent years, immune checkpoint inhibitors have emerged as the standard of care for patients with previously treated NSCLC. Data from the phase 3 OAK trial (NCT02008227) showed that atezolizumab improved OS over docetaxel in patients with locally advanced or metastatic NSCLC who had previously received 1 to 2 lines of chemotherapy, including at least 1 platinum-based treatment (HR, 0.75; 95% CI, 0.64-0.89; P = .0006).²

Additionally, findings from the phase 3 IMpower150 trial (NCT02366143) demonstrated that the 4-drug combination of atezolizumab, bevacizumab (Avastin), carboplatin, and paclitaxel, when used in the frontline treatment of patients with metastatic nonsquamous NSCLC, improved OS (HR, 0.78; 95% CI, 0.64-0.96; P = .02) and PFS (HR, 0.62; 95% CI, 0.52-0.74; P <.001) vs bevacizumab plus carboplatin/paclitaxel.³ Notably, survival benefit was also observed in patients with EGFR-mutated disease who had received prior treatment with EGFR TKIs.⁴

However, it remains unclear whether the first-line medication received prior to atezolizumab will impact the effectiveness of the immunotherapy in patients with NSCLC, according to the poster authors. Limited data are available regarding the prognosis of patients who receive immunotherapy in the frontline setting prior to atezolizumab. Additionally, osimertinib has obtained FDA approval for use as a frontline treatment in patients with EGFR-mutant, metastatic NSCLC, but the question of whether immunotherapy has a potential role in patients with driver mutations continues to be debated.

In the multicenter, observational, retrospective study, investigators set out to examine the clinical prognostic factors of patients with NSCLC who were receiving atezolizumab-containing regimens as second-line or later treatment in real-world practice in Taiwan.

Investigators identified patients who were diagnosed with advanced or metastatic NSCLC who were treated with at least 1 dose of atezolizumab in the second- or later-line settings by June 30, 2019. Patients were included in the analysis, irrespective of PD-L1 status. Investigators extracted patient-level data beginning from the date of diagnosis up until death, loss to follow-up, or until December 31, 2019, which was the end of the observation period.

To meet inclusion criteria for the study, patients had to have a histologically or cytologically confirmed diagnosis of NSCLC; had previously received at least 1 prior line of therapy for unresectable, locally advanced or metastatic NSCLC; and have underwent observation for at least 6 months following the first dose of atezolizumab.

If they received atezolizumab for unresectable, locally advanced, or metastatic NSCLC in the interventional clinical trial or they had less than 4 weeks of follow-up duration after their first atezolizumab dose, they were excluded from the analysis.

Investigators looked at clinical characteristics, treatment received prior to atezolizumab, response to treatment, as well as median PFS and median OS with atezolizumab.

A total of 128 patients who were given atezolizumab in the second-line setting or later were included in the analysis. Cohort 1 of the analysis comprised 13 patients who previously received immune checkpoint inhibitors and 115 patients who did not. Sixty-two patients had received EGFR TKIs before atezolizumab. Cohort 2 included 34 patients with nonsquamous NSCLC who had received treatment with an EGFR TKI; of these patients, 9 had been exposed to osimertinib and 25 had not.

Of the 128 participants, 30% (n = 38) were receiving an atezolizumab-containing regimen as second-line treatment, while 70% (n = 90) were receiving it as third- or later-line treatment. A total of 57 patients received single-agent atezolizumab.

Among the 13 patients in cohort 1 who received prior immunotherapy, the median age was 53.7 years, 61.5% were female, 53.8% were non-smokers, all had an ECOG performance status of 0 or 1, and more than half (53.8%) had adenocarcinoma. Additionally, the majority of patients (69.2%) had a PD-L1 tumor proportion score (TPS) of less than 50%.

In this subgroup, most (69.2%) had EGFR wild-type disease, received atezolizumab in a third or later line of treatment (69.2%) and as part of a combination (69.2%), and had prior radiotherapy. Almost 70% had previously received platinum chemotherapy, 53.8% had prior pemetrexed, and 38.5% had an EGFR TKI.

Notably, results from a multivariate analysis of prognostic factors for survival in patients who had received atezolizumab as second-line or later treatment indicated that prior immune checkpoint inhibitors (HR, 2.61; 95% CI, 1.38-4.91; P = .003) and poor performance status (HR, 3.17; 95% CI, 1.81-5.56; P <.001) were linked with poor prognosis.

In the 9 patients in cohort 2 who had prior osimertinib, the median age was 64.1 years, 88.9% were female, all were non-smokers, 55.6% had an ECOG performance status of 0 or 1, and 66.7% had a PD-L1 TPS of less than 50%. More than half (55.6%) had an EGFR deletion 19 mutation.

Additionally, all patients in this subgroup received atezolizumab in the third- or later-line settings, and the majority (77.8%) received it as part of a combination. Four patients received atezolizumab with chemotherapy, while 3 received it with chemotherapy and bevacizumab. Most patients received prior radiation. All patients had prior pemetrexed and platinum chemotherapy and 66.7% had previously received bevacizumab.

Results from a multivariate analysis of prognostic factors for survival in patients with EGFR-mutant disease who had previously received EGFR TKIs prior to atezolizumab revealed poor prognostic factors in atezolizumab-containing treatment, including previous osimertinib (HR, 5.49; 95% CI, 1.76-17.14; P = .003) and atezolizumab-containing treatment in the third- or later-line settings (HR, 7.56; 95% CI, 1.83-31.27; P = .001).

Additional studies with larger sample sizes are required to validate these findings, the authors of the poster concluded.

References

1. Wu S-G, Chiang C-L, Wang C-C, et al. The impact of prior immune checkpoint inhibitors or osimertinib treatment on NSCLC patients receiving atezolizumab treatment: a real world observation. Presented at: 2021 European Lung Cancer Conference; March 25-27, 2021; Virtual. Poster 146.
2. Fehrenbacher L, von Pawel J, Park K, et al. Updated efficacy analysis including secondary population results for OAK: a randomized phase III study of atezolizumab versus docetaxel in patients with previously treated advanced non–small cell lung cancer. J Thorac Oncol. 2018;13(8):1156-1170. doi:10.1016/j.jtho.2018.04.039
3. Sockinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378(24):2288-2301. doi:10.1056/NEJMoa1716948
4. Reck M, Mok TSK, Nishio M, et al. Atezolizumab plus bevacizumab and chemotherapy in non–small–cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir Med. 2019;7(5):387-401. doi:10.1016/S2213-2600(19)30084-0