Relapse patterns similar with atezolizumab or best supportive care in NSCLC subgroups
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Patients with early-stage non-small cell lung cancer who received best supportive care vs. atezolizumab after adjuvant chemotherapy had a higher relapse rate, but relapse patterns appeared similar between the groups, study results showed.
The interim DFS analysis of the randomized phase 3 IMpower010 trial, presented during the virtual ESMO Congress 2021 and published simultaneously in The Lancet, also showed a trend toward delayed relapse with atezolizumab (Tecentriq, Genentech) among patients with PD-L1 expression of at least 1% of tumor cells (PD-L1 TC 1%) and stage II to stage IIIA disease. Those who received best supportive care had higher rates of immunotherapy use after relapse.
“Up to 60% of patients with stage I, II or III [NSCLC] still experience disease relapse despite treatment with curative intent, including surgery,” Enriqueta Felip, MD, head of the thoracic and head and neck cancer unit within the oncology department of Vall d’Hebron University Hospital in Spain, said during a presentation. “IMpower010 is the first phase 3 study with immunotherapy to demonstrate a [DFS] improvement in the adjuvant lung cancer setting after complete surgical resection and platinum-based chemotherapy. Here we report sites of disease relapse and post-relapse treatment in IMpower010 at the time of the prespecified [DFS] interim analysis.”
IMpower010 included 1,280 patients with completely resected stage IB to stage III NSCLC who received as many as four cycles of cisplatin-based chemotherapy. Researchers randomly assigned 1,005 patients without progression after chemotherapy to either 1,200 mg atezolizumab every 3 weeks for 16 cycles until disease relapse or unacceptable toxicity (n = 507) or best supportive care (n = 498).
Investigator-assessed DFS tested hierarchically, first among 476 patients with stage II to stage IIIA disease and PD-L1 TC 1%, then among all 882 randomly assigned patients with stage II to stage IIIA disease and finally among all 1,005 patients in the intention-to-treat population, served as the primary endpoint. Researchers also conducted exploratory analyses of relapse sites and post-relapse treatment.
Results presented during this year’s ASCO Annual Meeting showed atezolizumab, when compared with best supportive care, reduced the risk for recurrence or death by 34% among patients with stage II to stage IIIA disease and PD-L1 TC 1% (median DFS, not evaluable vs. 35.3 months; HR = 0.66; 95% CI, 0.5-0.88) and by 21% among all randomly assigned patients with stage II to stage IIIA disease (median DFS, 42.3 months vs. 35.3 months; HR = 0.79; 95% CI, 0.64-0.96). The difference in DFS among the intent-to-treat population had not crossed the boundary for statistical significance (median, not evaluable vs. 37.2 months). The investigators observed the DFS benefit with atezolizumab in the randomly assigned stage II to stage IIIA population with increasing PD-L1 expression (TC < 1%, HR = 0.97; 95% CI, 0.72-1.31; TC 1-49%, HR = 0.87; 95% CI, 0.6-1.26; TC 50; HR = 0.43; 95% CI, 0.27-0.68).
Incidence of disease relapse was higher in the best supportive care vs. atezolizumab group in all three subgroups (PD-L1-positive stage II-IIIA, 44.7% vs. 29.4%; all stage II-IIIA, 43% vs. 33.3%; intention to treat, 40.8% vs. 30.8%). An analysis of patterns of relapse revealed no clear differences among the subgroups. In the intention-to-treat population, 37.8% of patients who received atezolizumab experienced locoregional-only relapse vs. 36.9% in the best supportive care group, 42.9% vs. 40.4% had distant-only relapse and 17.3% vs. 18.7%. had both locoregional and distant relapse. These patterns were consistent in the other subgroups.
Patients in the PD-L1-positive stage II-IIIA group who received atezolizumab vs. best supportive care had a longer median time to any relapse (17.6 months vs. 10.9 months). Felip noted the small sample size of the analysis. Time to relapse was similar between groups in the other two subgroups.
About two-thirds of patients in all subgroups received additional systemic anticancer therapy after relapse. “As suspected, more patients received immunotherapy in the best supportive care arm, approximately 32%, when compared to the atezolizumab arm, in which approximately 12% of the patients received immunotherapy at disease recurrence,” Felip said.
The treatment groups had similar rates of radiotherapy and surgery after relapse across study populations.
“At this [DFS] analysis, we have observed similar patterns of relapse between the study arms,” Felip said. “Time to relapse appeared to favor atezolizumab vs. best supportive care in the group of patients with stage II to IIIA and PD-L1-positive tumors.”
References:
Felip E, et al. Abstract LBA9. Presented at: European Society for Medical Oncology Congress (virtual meeting); Sept. 17-21, 2021.
Felip E, et al. The Lancet. 2021;doi:10.1016/S0140-6736(21)02098-5.
Perspective
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Swapnil Rajurkar, MD
Patients with early-stage NSCLC are at a considerable risk for recurrence even after surgical resection. A Cochrane meta-analysis showed a 4% absolute OS benefit in patients who received adjuvant chemotherapy after surgical resection.
In patients with stage IB to stage IIIA EGFR mutation-positive NSCLC, DFS was significantly longer among those who received osimertinib (Tagrisso, AstraZeneca) than among those who received placebo, which led to the FDA approval of Tagrisso in February. An OS benefit has not yet been demonstrated.
Currently, there is no FDA-approved drug for patients with early-stage non-EGFR-mutated NSCLC who have undergone resection and adjuvant chemotherapy. IMpower010 was the first randomized phase 3 study to show DFS improvement with atezolizumab in an interim analysis presented by Wakelee and colleagues at this year’s ASCO Annual Meeting. The improvement in DFS was seen with increasing PD-L1 expression. Application for Tecentriq approval is being reviewed under the FDA’s Real-Time Oncology Review pilot program.
In this abstract, Felip and colleagues found there was no clear difference in the pattern of relapse (including CNS only) between the atezolizumab and best supportive care groups. This is reassuring. There is no information provided regarding symptomatic vs. asymptomatic metastases.
As expected, more patients in the best supportive care group received immunotherapy after they relapsed. With increasing use in the metastatic setting, most clinicians have become comfortable with monitoring and managing toxicities of immunotherapy agents. Clinicians will wait for FDA approval before utilizing atezolizumab in the adjuvant setting.
References:
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Felip E, et al. Abstract LBA9. Presented at: European Society for Medical Oncology Congress (virtual meeting); Sept. 17-21, 2021.
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