Immunotherapy and Targeted Therapies in NSCLC: Phase 3 Data From ESMO 2022

Human lungs with tumors, showing lung cancer or bronchial carcinoma, 3d illustration
Results from the CodeBreak 200, EMPOWER-Lung 1, IPSOS, and ADAURA trials highlight the efficacy of immunotherapy and targeted therapies in non-small cell lung cancer.

Late-breaking abstracts presented at ESMO Congress 2022 highlight the efficacy of immunotherapies and targeted therapies in non-small cell lung cancer (NSCLC). 

Long-term survival data from the phase 3 EMPOWER-Lung 1 trial showed that cemiplimab can improve progression-free survival (PFS) and overall survival (OS), compared with chemotherapy, in patients with NSCLC.1 

Results from the phase 3 IPSOS trial showed that first-line atezolizumab can improve OS, compared with chemotherapy, in patients with stage IIIB/IV NSCLC who are ineligible for platinum-containing therapy.2

The phase 3 CodeBreak 200 trial showed that sotorasib can improve PFS, compared with docetaxel, in patients with previously treated, KRASG12C-mutated NSCLC.3

And updated results from the phase 3 ADAURA trial showed a continued disease-free survival (DFS) benefit with adjuvant osimertinib vs placebo in patients with completely resected, stage IB-IIIA, EGFR-mutated NSCLC.4

EMPOWER-Lung 1 Trial

Updated results from the EMPOWER-Lung 1 study support the use of cemiplimab as a first-line, chemotherapy-free treatment option for advanced NSCLC, according to study presenter Mustafa Özgüroğlu, MD, of İstanbul University-Cerrahpaşa in Turkey.1

The study ( Identifier: NCT03088540) included 712 patients with treatment-naïve, advanced NSCLC who were randomly assigned to receive cemiplimab (n=357) or investigator’s choice of chemotherapy (n=355). 

The median OS was 23.4 months in the cemiplimab arm and 13.7 months in the chemotherapy arm (hazard ratio [HR], 0.63; 95% CI, 0.52-0.77; P =.0001). The median PFS was 6.3 months and 5.3 months, respectively (HR, 0.56; 95% CI, 0.47-0.67; P =.0001).

These results are notable especially because of the high crossover rate from the chemotherapy arm to the cemiplimab arm (75%), Dr Özgüroğlu said in an interview. 

He also pointed out that patients with PD-L1 levels of at least 50% had a greater PFS and OS benefit with cemiplimab. In the PD-L1-high group, the median PFS was 8.1 months in the cemiplimab arm and 5.3 months in the chemotherapy arm (HR, 0.51; 95% CI, 0.42-0.62; P =.0001). The median OS was 26.1 months and 13.3 months, respectively (HR, 0.57; 95% CI, 0.46-0.71; P =.0001). 

Dr Özgüroğlu and colleagues also evaluated the effects of continued cemiplimab in combination with chemotherapy in a subset of patients whose disease progressed on cemiplimab. This is something prospective trials have not attempted before, according to Dr Özgüroğlu.

There were 64 patients in the cemiplimab arm who went on to receive cemiplimab plus chemotherapy after progression. The overall response rate was 31.3%, with 3 patients achieving a complete response. The median OS was 15.1 months in the post-progression period and 27.4 months overall for this patient group.

Dr Özgüroğlu noted that these patients benefited from cemiplimab plus chemotherapy without additional safety concerns. He speculated that adding chemotherapy might increase tumor immunogenicity and change the tumor microenvironment. He stressed, however, that the benefit of this combination was observed in an exploratory analysis, so further study is needed. 

“We definitely need a comprehensive update on the post-progression data, and this is of key importance,” said study discussant Martin Reck, MD, PhD, of Großhansdorf Hospital Lung Clinic in Hamburg, Germany. 

“We have seen an interesting exploratory signal for a new post-progression strategy of immuno-monotherapy. The scheduling and the placing of immunotherapy combinations still needs to be determined.” 


In the phase 3 IPSOS trial, first-line atezolizumab improved OS for patients with stage IIIB/IV NSCLC who were ineligible for platinum therapy.2

Siow Ming Lee, MBBS, PhD

“Many patients cannot receive standard platinum doublets,” study presenter Siow Ming Lee, MBBS, PhD, of University College London Hospitals in the UK, said in an interview. “They are mainly elderly people with poor performance status or with significant comorbidities receiving multiple medications that cannot tolerate platinum doublet chemotherapy.” 

The IPSOS trial ( Identifier: NCT03191786) included 453 such patients, and they were randomly assigned to receive atezolizumab (n=302) or single-agent chemotherapy with vinorelbine or gemcitabine (n=151). 

At a median follow-up of 41.0 months, the median OS was significantly longer in the atezolizumab arm than in the chemotherapy arm — 10.3 months and 9.2 months, respectively (HR, 0.78; 95% CI, 0.63-0.97; P =.028). The 24-month OS rate was 24.3% and 12.4%, respectively.

Dr Lee noted that IPSOS did not restrict patients by PD-L1 status or performance status, which made the trial’s positive results all the more striking. 

“Just imagine, the average age was 75 years, half of patients were PD-L1-negative, and despite this, we had an HR of 0.78 for OS, our primary objective,” Dr Lee said. “One in 4 patients were alive at a 2-year time point.” 

This study enrolled patients who are historically excluded or underrepresented in NSCLC trials but who represent most of the NSCLC patients diagnosed and treated around the world, said study discussant Natasha Leighl, MD, of Princess Margaret Cancer Centre in Toronto, Canada.

She added that the OS results mean atezolizumab scores a 5 out of 5 on the ESMO clinical benefit scale. “Perfect marks,” she said. “Couldn’t get better.”

On the other hand, there was no significant difference in PFS between the treatment arms. The median PFS was 4.2 months in the atezolizumab arm and 4.0 months in the chemotherapy arm (HR, 0.87; 95% CI, 0.70-1.07). 

Dr Leighl also noted that financial toxicity is greater with atezolizumab than with chemotherapy. She cited monthly costs of around $13,805 for atezolizumab, $260 for vinorelbine, and $4000 for gemcitabine.

“Financial toxicity is something we eventually will need to address across the world in this new era of immunotherapy treatment for lung cancer,” Dr Lee agreed.

This article originally appeared on Cancer Therapy Advisor