While the treatment landscape for lung cancer continues to grow, nurses must stay up-to-date on the most recent advances and approvals across each subgroup of patients.
At the 3rd Annual School of Nursing Oncology, Beth Eaby-Sandy, MSN, CRNP, thoracic oncology nurse practitioner, Abramson Cancer Center, University of Pennsylvania, discussed the various treatment options for patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).
Locally Advanced Stage III NSCLC
Occurring in about 25% of patients with NSCLC, treatment for locally advanced, stage III disease was typically treated with concurrent chemotherapy plus radiation. However, the median progression-free survival (PFS) for these patients is 8 to 10 months, and the 5-year survival rate is only about 15% to 20%.
“Most of these patients will recur and die of their lung cancer,” Eaby-Sandy said.
After several years of no treatment advances for this patient population, durvalumab (Imfinzi) was approved as the only immunotherapy for these patients at the time. In the randomized, double-blind, placebo-controlled, multicenter, international phase III trial of durvalumab plus chemotherapy/radiation, patients treated with the regimen demonstrated superior PFS and overall survival (OS) compared with placebo.
More recently, pembrolizumab (Keytruda) was also approved for patients with locally advanced NSCLC in April – however, Eaby-Sandy noted the patients in the trial for which the drug was tested actually had stage IV disease. “Patients in the study had stage III non-small cell lung cancer, but they were not candidates for, or refused concurrent chemotherapy, radiation or surgery,” she added. “So, really, these patients were treated as stage IV, even though they were clinically and pathologically diagnosed as stage III.”
Metastatic Non-Squamous NSCLC
Currently, nivolumab (Opdivo), pembrolizumab, and atezolizumab (Tecentriq) are approved for a variety of indications in patients with metastatic NSCLC.
In the open-label phase III Keynote-024 trial, researchers evaluated pembrolizumab compared with platinum-based chemotherapy. The study was the first time a single agent immunotherapy was superior to platinum-based chemotherapy. Moreover, the agent is generally less toxic than chemotherapy.
Next, researchers evaluated chemotherapy plus pembrolizumab compared with chemotherapy alone in the Keynote-189 trial. At 6 months, 69% of patients were alive in the combination arm compared with 49% in the chemotherapy arm.
With such success, researchers then evaluated a 4-drug regimen of atezolizumab, carboplatin, paclitaxel, and bevacizumab (Avastin) in the IMpower150 trial. The regimen was superior in OS compared with carboplatin, paclitaxel, and bevacizumab (19.2 months vs. 14.7 months; P = .02). Eaby-Sandy explained this regimen is typically used in patients who require treatment with targeted therapies. “This can be a very toxic (regimen),” she said. “So, it is rare that I use the 4-drug regimen.”
Similar to non-squamous NSCLC, chemotherapy plays the same role in treatment. Currently, there are 16 approved treatments for the front-line setting.
In the Keynote-407 trial, researchers added pembrolizumab to carboplatin plus paclitaxel or nab-paclitaxel – demonstrating an improved PFS and OS among patients. This highlights the fact that immunotherapy plays a role in this patient population, Eaby-Sandy said.
In the second-line setting, the National Comprehensive Cancer Network recommends for treatment with docetaxel with or without ramucirumab (Cyramza); pemetrexed; nivolumab, pembrolizumab, or atezolizumab if they were not used in the front-line setting; and gemcitabine.
Genetic biomarkers for NSCLC include KRAS, EGFR, ALK, EGFR, ERBB2, BRAF, V600, NRAS, Non-V600E, PIK3CA, G719X, MEK1, MET, and L861Q. “The most common patients that would have a mutation in lung cancer would be adenocarcinoma patients and never-smokers or distant smokers,” Eaby-Sandy said. “However, we find them sometimes in smokers. Therefore, every lung cancer patient who is stage IV with non-squamous (NSCLC) should be molecularly tested.”
To treat patients with EGFR-mutant NSCLC, erlotinib (Tarceva), gefitinib, afatinib (Gilotrif), osimertinib (Tagrisso), and dacomitinib (Vizimpro) are used. However, of note, osimertinib is the preferred option. To support this, the FLAURA trial evaluated the use of osimertinib versus erlotinib or gefitinib in the first-line setting, which showed an improved PFS of 18.9 months compared with 10.2 months, respectively (HR, 0.46; 95% CI, 0.37-0.57; P < .0001).
To treat patients with ALK-positive NSCLC, crizotinib (Xalkori), ceritinib (Zykadia), alectinib (Alecensa), brigatinib (Alunbrig), and lorlatinib (Lorbrena) are approves for these patients. Alectinib is the preferred treatment, Eaby-Sandy said. In a trial designed to evaluate alectinib versus crizotinib, alectinib demonstrated a significant improvement in PFS, with some improvement in OS. Importantly, there was a significant improvement in intracranial response, and the agent was well tolerated.
ROS1 – a biomarker most common in younger, never smokers – is effectively treated with crizotinib, the only approved therapy approved for these patients. However, lorlatinib, entrectinib, TPX-0005, and the combination use of ceritinib and trametinib are all under clinical investigation.
For patients with a BRAF mutation – which makes up about 25% of NSCLC and usually occurs in smokers – dabrafenib plus trametinib was approved for the first-line setting based on phase II trial results.
Small Cell Lung Cancer
After 25 year, SCLC – which only makes up 13% of lung cancers – has finally seen advances in recent years, Eaby-Sandy said.
Due to its aggressive nature, chemotherapy should be started immediately in these patients. Etoposide and platinum chemotherapy have been the mainstay; however, immunotherapy may now have a role.
In the global, double-blind, randomized, placebo-controlled phase I/III IMpower 133 trial, researchers evaluated front-line atezolizumab plus carboplatin and etoposide in patients with early-stage disease. The immunotherapy regimen demonstrated superior OS compared with placebo plus chemotherapy (51.7% vs. 38.2%, respectively). In addition, median OS was 12.3 months compared with 10.3 months in the immunotherapy group (HR, 0.70; 95% CI, 0.54-0.91; P = .0069).
“It’s exciting to see that half of these people are living to 1 year,” Eaby-Sandy said.
With this, in the last 12 months, nivolumab, pembrolizumab, and atezolizumab have all been approved to treat patients with SCLC.
“There are a lot of changes in treatment for non-small cell lung cancer. Immunotherapy is our mainstay. Targeted therapies are evolving, and we’re making improvement with those agents to see what one works best,” Eaby-Sandy said.
Eaby-Sandy B. Lung Cancer: Essentials for Oncology Nurses. Presented at: 3rd Annual School of Nursing Oncology; August 2-3, 2019; San Diego, CA.