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Gene testing remains an important aspect of lung cancer treatment
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ORLANDO — Gene testing is still very important to determine targeted therapies for patients with lung cancer despite the widespread use of immunotherapy, according to a presenter at Community Oncology Alliance Conference.
When deciding a treatment regimen for patients with lung cancer, it’s important to remember that immunotherapy alone may not be enough for some patients, the presenter added.
“PD-L1, EGFR, ALK, BRAF, ROS1 and NTRK are a growing list of targetable mutations and alterations that help drive benefit to distinct molecular groups of patients,” Melissa L. Johnson, MD, associate director for lung cancer research at Sarah Cannon Research Institute, said during the presentation. “Stay tuned for tumor mutational burden, which perhaps we can find in the blood as well as other genes like MET and RET.”
Johnson pointed to several recent studies that have demonstrated the benefit of testing and shown positive results for patients with lung cancer. These included:
KEYNOTE-042 — Demonstrated that first-line pembrolizumab (Keytruda, Merck) conferred longer median OS than chemotherapy among patients with non-small cell lung cancer and PD-L1 expression. Researchers randomly assigned 1,274 patients with locally advanced or metastatic NSCLC without EGFR mutations or ALK translocation to receive 200 mg pembrolizumab every 3 weeks (n = 637) or investigator’s choice of maximum six cycles of paclitaxel plus carboplatin or pemetrexed plus carboplatin (n = 637) with optional pemetrexed maintenance for nonsquamous disease. Pembrolizumab significantly improved OS among patients with PD-L1 tumor proportion score of more than 50% (median OS, 20 months vs. 12.2 months; HR = 0.69; 95% CI, 0.56-0.85), more than 20% (17.7 months vs. 12 months; HR = 0.77; 95% CI, 0.64-0.92) and more than 1% (16.7 months vs. 12.1 months; HR = 0.81; 95% CI, 0.71-0.93);
KEYNOTE-024 — Evaluated the safety and efficacy of pembrolizumab vs. platinum-based chemotherapy as first-line treatment for patients with NSCLC who had PD-L1 tumor proportion scores of 50% or greater but did not have EGFR/ALK aberrations. Researchers randomly assigned 305 patients to 200 mg pembrolizumab (n = 154) every 3 weeks for up to 2 years or chemotherapy (n = 151). An independent data and safety committee recommended the trial be discontinued after an interim analysis — performed at median follow-up of 11.2 months — showed significant improvements in PFS (HR = 0.5; 95% CI, 0.37-0.68) and OS (HR = 0.6; 95% CI, 0.41-0.89) with pembrolizumab;
KEYNOTE-189 — Included 616 previously untreated patients with untreated stage IV nonsquamous NSCLC who had no sensitizing EGFR or ALK alterations. Researchers randomly assigned 410 patients to pemetrexed plus pembrolizumab and either cisplatin or carboplatin, followed by pembrolizumab and pemetrexed maintenance. The other 206 patients received pemetrexed plus placebo and either cisplatin or carboplatin, followed by maintenance with placebo plus pemetrexed. Patients assigned the pemetrexed-pembrolizumab regimen achieved significantly longer median PFS (8.8 months vs. 4.9 months; HR = 0.52; 95% CI, 0.43-0.64) and OS (not reached vs. 11.3 months; HR = 0.49; 95% CI, 0.38-0.64). OS did not differ significantly based on PD-L1 tumor proportion score;
KEYNOTE0-407 — Included 559 patients with metastatic squamous NSCLC who had received no prior systemic treatment for metastatic disease regardless of PD-L1 expression. Investigators randomly assigned 278 patients to receive 200 mg pembrolizumab and carboplatin every 3 weeks for four cycles, plus paclitaxel every 3 weeks for four cycles or nab-paclitaxel on days 1, 8 and 15 of every 3-week cycle for four cycles, followed by 200 mg pembrolizumab every 3 weeks. The other 281 patients received placebo plus the same chemotherapy regimen. Patients assigned the pembrolizumab regimen achieved significantly longer OS (median, 15.9 months vs. 11.3 months; HR = 0.64; 95% CI, 0.49-0.85) and PFS (median, 6.4 months vs. 4.8 months; HR = 0.56; 95% CI, 0.45-0.7). Researchers also reported a higher overall response rate in the pembrolizumab group (58% vs. 35%; P = .0008);
IMpower133 — Researchers randomly assigned 403 treatment-naive patients with extensive-stage small cell lung cancer 1:1 to 1,200 mg atezolizumab (Tecentriq, Genentech/Roche) or placebo on day 1 with carboplatin (area under the curve 5 mg/mL/min on day 1) and etoposide (100 mg/m2 IV on days 1, 2 and 3 of each 21-day cycle for four cycles). Following the first four cycles, patients received 1,200 mg atezolizumab or placebo once every 3 weeks until progression or unacceptable toxicity. Data showed the combination of atezolizumab and chemotherapy significantly extended median OS in the intention-to-treat population compared with chemotherapy alone (12.3 months vs. 10.3 months; HR = 0.7; 95% CI, 0.54-0.91). The combination also conferred longer median PFS (5.2 months vs. 4.3 months; HR = 0.77; 95% CI, 0.62-0.96);
CheckMate-026 — Evaluated nivolumab (Opdivo, Bristol-Myers Squibb) in 541 previously untreated patients with advanced NSCLC whose tumors expressed PD-L1. Patients received nivolumab 3 mg/kg via IV every 2 weeks or investigator’s choice of chemotherapy. The study failed to meet its primary endpoint of PFS among patients whose tumors expressed PD-L1 at levels of 5% or more; and
CheckMate-227 — Included 1,739 patients with chemotherapy-naive, histologically confirmed stage IV or recurrent NSCLC and no known sensitizing EGFR or ALK mutations. In part 1a, researchers assigned patients with PD-L1 expression of 1% or higher (n = 1,189) to one of three regimens: nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (n = 396), nivolumab monotherapy dosed at 240 mg every 2 weeks (n = 396), or histology-based doublet chemotherapy (n = 397). In part 1b, investigators assigned patients with PD-L1 expression less than 1% (n = 550) to one of three regimens: nivolumab plus ipilimumab (n = 187; median age, 63 years), nivolumab 360 mg every 3 weeks plus histology-based chemotherapy (n = 177), or chemotherapy alone (n = 186). The median PFS was 5.6 months in the nivolumab-chemotherapy group and 4.7 months in the chemotherapy group, for an HR of 0.74 (95% CI, 0.58-0.94).
“To summarize, do you still need to test? Yes,” Johnson said. “[As the studies have shown], most patients will probably get [immunotherapy] as part of their first-line regimen, but this alone will not be enough for some.” – by John DeRosier
Reference:
Johnson M.L. Latest advances and updates in lung cancer. Presented at: Community Oncology Alliance Conference; April 4-5, 2019; Orlando.
Disclosures: HemOnc Today could not confirm Johnson’s relevant disclosures at time of reporting.