From the Guidelines
For patients with lung adenocarcinoma, particularly those with metastatic disease, the treatment of choice involves immunotherapy with PD-L1 and PD-1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, irrespective of PD-L1 expression, as recommended by the most recent guidelines 1.
Treatment Approach
The approach to treating lung adenocarcinoma depends on the stage of the disease and the presence of actionable mutations.
- For early-stage disease, surgical resection is the primary treatment, often followed by adjuvant chemotherapy.
- For locally advanced disease, a multimodal approach combining chemotherapy, radiation, and possibly surgery is recommended.
- For metastatic disease, treatment is guided by molecular testing for actionable mutations, with patients receiving targeted therapies based on their mutation status.
Immunotherapy
Immunotherapy has become a cornerstone in the treatment of metastatic non-small cell lung cancer (NSCLC), including adenocarcinoma.
- PD-L1 and PD-1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, are recommended for most patients with advanced, previously treated, PD-L1 inhibitor-naive NSCLC, irrespective of PD-L1 expression 1.
- Pembrolizumab is specifically recommended for patients with previously treated NSCLC with PD-L1 expression > 1% 1.
- Nivolumab is recommended in both squamous and non-squamous NSCLC 1.
Chemotherapy
For patients not suitable for immunotherapy, second-line chemotherapy is recommended.
- Comparable options as second-line therapy consist of pemetrexed, for NSCC only, or docetaxel, with a more favourable tolerability profile for pemetrexed 1.
- Treatment may be prolonged if disease is controlled and toxicity acceptable 1.
Targeted Therapies
Targeted therapies play a crucial role in the treatment of lung adenocarcinoma, particularly for patients with actionable mutations.
- Patients with EGFR mutations may receive osimertinib, ALK-positive patients may receive alectinib, while ROS1-positive patients may benefit from crizotinib or entrectinib.
- Erlotinib represents a potential second/third-line treatment option in particular for patients not suitable for immunotherapy or second-line chemotherapy in unknown EGFR status or EGFR WT tumours 1.
From the FDA Drug Label
Non-Small Cell Lung Cancer (NSCLC) in combination with pemetrexed and platinum chemotherapy, as first-line treatment of patients with metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations. as a single agent for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is: Stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.
Lung Cancer Treatments for Adenocarcinoma:
- Pembrolizumab (KEYTRUDA) is indicated for the treatment of patients with metastatic nonsquamous NSCLC, including adenocarcinoma, in combination with pemetrexed and platinum chemotherapy as first-line treatment, with no EGFR or ALK genomic tumor aberrations.
- Pembrolizumab (KEYTRUDA) is also indicated as a single agent for the first-line treatment of patients with NSCLC, including adenocarcinoma, expressing PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
- Docetaxel (IV) is indicated for the treatment of patients with unresectable, locally advanced or metastatic NSCLC, including adenocarcinoma, previously treated with platinum-based chemotherapy. 2 3
From the Research
Lung Cancer Treatments for Adenocarcinoma
- The most common histology of non-small cell lung cancer (NSCLC) in the United States is adenocarcinoma, followed by squamous cell, large cell, and not otherwise specified 4.
- For patients with a preserved performance status (PS), double agent platinum-based therapy extends survival, improves quality of life (Qol), and reduces disease-related symptoms 4.
- The addition of a targeted agent (bevacizumab, an antiangioegenesis agent, or cetuximab, an antibody against the epidermal growth factor receptor [EGFR]) to platinum-based therapy has yielded an improvement in survival compared with platinum-based therapy alone 4.
- Patients with adenocarcinoma may benefit from initial therapy with an EGFR tyrosine kinase inhibitor, especially those with a light or never-smoking history 4.
- Osimertinib has largely displaced first- and second-generation EGFR TKIs, including gefitinib, erlotinib, and afatinib, in the management of EGFR-mutated NSCLC, with a progression-free survival (PFS) exceeding 18 months 5.
- Alectinib and brigatinib, very specific ALK inhibitors, have proven superior to the erstwhile standard crizotinib in treatment-naive ALK+ NSCLC, with a PFS exceeding 2 to 3 years 5.
Treatment Options
- Surgery, radiation, chemotherapy, immunotherapy, or molecularly targeted therapy is used to treat NSCLC 6.
- Targeted treatments and immunotherapy have achieved improvement at a breakneck pace in recent years 6.
- Therapy must be customized for each patient based on the specific medical condition, as well as other variables 6.
- Accurate NSCLC sub-classification is critical for tailored treatment, according to the latest World Health Organization standards 6.
Rare Cases
- A rare case of lung adenocarcinoma harboring EGFR mutation and EML4-ALK fusion gene has been reported, with no clinical benefit obtained from erlotinib as the third line therapy 7.
- The therapeutic choice for patients with more than one driver mutations is unclear, and further understanding of the lung cancer molecular biology and the biomarker information is needed 7.