Toripalimab plus initial chemotherapy prolongs PFS, OS in non-small cell lung cancer
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The addition of toripalimab to first-line chemotherapy prolonged PFS and OS among patients with advanced non-small cell lung cancer without EGFR/ALK mutations, according to study results.
Results of the phase 3 CHOICE-01 trial, presented during a ASCO Plenary Series session, specifically showed PFS and OS improvement with the combination among patients with mutations in the FA-PI3K-Akt pathway.
“These results support toripalimab [Junshi Biosciences] combined with chemotherapy as a first-line treatment option for patients with advanced NSCLC without driver mutations,” Jie Wang, MD, researcher at National Cancer Center/Cancer Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, said during her presentation.
Rationale and methods
The randomized, double-blind, placebo-controlled, multicenter, phase 3 CHOICE-01 trial included 465 patients with treatment-naive advanced NSCLC without EGFR/ALK mutations.
Researchers randomly assigned patients 2:1 to 240 mg toripalimab (n = 309; median age, 63 years; 79.9% men) or placebo (n = 156; median age, 61 years; 83.3% men) plus standard chemotherapy, followed by maintenance of toripalimab or placebo combined with standard of care until disease progression or intolerable toxicity or after 2 years of treatment.
PFS per RECIST version 1.1 served as the primary endpoint, with a data cutoff of Oct. 31.
Key findings
Results of the prespecified final PFS analysis showed median PFS of 8.4 months (95% CI, 7.7-9.6) in the toripalimab-plus-chemotherapy group vs. 5.6 months (95% CI, 5.5-6.8) in the chemotherapy-alone group (stratified HR for disease progression or death = 0.49; 95% CI, 0.39-0.61). Patients who received the toripalimab combination had a 1-year PFS rate of 36.7% vs. 17.2% with chemotherapy alone.
Median OS had not yet been reached at the interim analysis among patients in the toripalimab group compared with 17.1 months in the placebo group (HR = 0.69; 95% CI, 0.52-0.92).
“In addition, PFS and OS benefits were observed regardless of PD-L1 expression status, and genomic analysis using whole-exome sequencing revealed that patients with high tumor mutational burden were associated with significantly better PFS in the toripalimab group,” Wang said.
The toripalimab and chemotherapy-alone groups had similar rates of grade 3 or higher treatment-emergent adverse events (78.6% vs. 82.1%) and serious adverse events (44.8% vs. 35.3%). The toripalimab group had a higher rate of adverse events that led to treatment discontinuation (14.3% vs. 3.2%) and more fatal adverse events (5.5% vs. 2.6%).
Researchers additionally observed significantly longer PFS among patients with high tumor mutational burden in the toripalimab group compared with the chemotherapy-alone group (13.1 months vs. 5.5 months), whereas patients in the chemotherapy-alone group who had mutations in the FA-PI3K-Akt pathway or IL-7 signaling pathways had significantly longer PFS (8.9 months vs. 4.2 months).
Implications
“These results confirm that the combination of immunotherapy and chemotherapy improves survival of patients with previously untreated advanced NSCLC that do not have driver mutations,” Maximilian Diehn, MD, PhD, radiation oncologist at Stanford Health Care and an ASCO lung cancer expert, said in a press release.
Perspective
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We have made tremendous progress within the past 2 decades for patients with metastatic NSCLC. OS has significantly increased from less than 1 year in 2002 with the use of combination chemotherapy to more than 2 years now in 2022 with the integration of immunotherapy. Long-term outcomes confirm that we are making a meaningful difference in OS, with 5-year percentages greater than 30% for patients diagnosed with stage IV disease, and survival outcomes confirm our current practice to integrate chemotherapy with immunotherapy.
The CHOICE-01 trial was very well done. As a practicing oncologist, I have no choice but to compare the data in a cross-trial fashion to evaluate how I may use this agent in practice. Results from this current trial are very comparable to key landmark trials. Building upon the initial success of immunotherapy in 2016, several trials have firmly established the practice to not only use immuno-monotherapy but also chemoimmunotherapy, including quadruplet regimens.
Should PFS serve as primary endpoint? Wang and colleagues conducted a simulation algorithm of trial data and found that PFS HRs weakly correlated with OS HRs and suggest we should move away from using PFS as a primary endpoint, as it does not translate into an OS endpoint. Does PFS have a meaningful impact on patients? Patients with advanced cancer want a treatment that will prolong survival and urge us to convert PFS to an interval instead.
Today we have so many treatment choices for these patients. One of the ways we can see if a drug is valuable would be if it came as a cost advantage. By this mechanism, it would drive up competition and decrease health care costs that may be meaningful to society. We as a global community must ensure equitable access to these drugs. While this is easier said than done, one of the ways to ensure this is with the use of multiregional clinical trials with diverse populations and coordinated worldwide regulatory submissions to be pursued to ease this inequity.
In 2022, we have many choices, including the choice to no longer consider chemotherapy alone as an adequate comparator arm for first-line treatment for patients with NSCLC. We have a choice to prioritize OS as the primary endpoint — to focus on innovation that moves the needle on efficacy, tolerability and cost — and we have the choice to invest in partnerships that provide global access to new drugs and collaborate to develop biomarkers and identify patients who are both benefited and potentially harmed by immunotherapy.
HemOnc Today Editorial Board Member
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Wang J, et al. Abstract 362936. Presented at: ASCO Plenary Series (virtual); March 15, 2022.
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