Advances in Lung Cancer Treatment - 2017 and 2018

Lung cancerremains the most common cancer and the leading cause of cancer death worldwide. Nevertheless, visible advances have occurred in its treatment since 2010. Particularly in the last two years, the results of immunotherapies and targeted smart drugs in stage 4 non-small-cell lung cancer have been exciting for all of us..

• Small-cell and non-small-cell lung cancer – What are the differences?

1. Immunotherapy Durvalumab Entered Use in Stage 3 Non-Small-Cell Lung Cancer (March 2018)

25% of patients with non-small-cell lung cancer are diagnosed at stage 3, and the main treatment for a large proportion is chemotherapy combined with radiation therapy. Despite this combined treatment, recurrence risk is high. Immunotherapies remove suppression of the immune system, allowing our own defense cells to attack tumor cells. Their effective use in stage 4 lung cancer that has spread through the body prompted consideration for stage 3 patients as well.

In stage 3 non-small-cell lung cancer, 700 patients received radiation therapy and at least two cycles of platinum -containing chemotherapy. Some patients were then observed without treatment, while the other group received the PD-L1 inhibitor durvalumab (Imfinzi). Durvalumab extended the time to recurrence by an additional 12 months (1).

While many studies of preventive drugs following primary treatment in stage 3 non-small-cell lung cancer failed, durvalumab changed the strategy for these patients. This study led to durvalumab's entry into use in stage 3 non-small-cell lung cancer with FDA approval.

2. Afatinib Received FDA Approval for First-Line Treatment of EGFR-Positive Lung Cancer (January 2018)

In non-small-cell lung adenocarcinoma, 20% have an EGFR mutation , against which many drugs have been developed. One, afatinib, could previously be used when resistance to earlier targeted drugs developed or those drugs could not be tolerated.

Afatinib's new use is based on subgroup analyses of three clinical studies. The analysis found a treatment benefit rate of 66%, with 1 year exceeded by 52% of patients continuing to benefit. Following this analysis, in January 2018 the United States Food and Drug Administration, FDA, approved the targeted drug afatinib (Glotrif) for stage 4 EGFR mutation-positive non-small-cell lung cancer as first-line treatment.

3. Surgery or Radiotherapy in Early-Stage Lung Cancer? (January 2018)

Surgery is the standard treatment for early-stage non-small-cell lung cancer. However, advances in radiotherapy and interventional radiology (nonsurgical cancer treatment) technologieshave brought nonsurgical options into consideration. One technological innovation in radiation treatment is stereotactic body radiation therapy (SBRT). With this method, the total calculated radiation dose is delivered in one or a few sessions, aiming to destroy the tumor completely with beams focused on it from many directions.

The study evaluated 84.839 early-stage lung cancer patients registered in the United States National Cancer Database. Patients had no distant-organ metastasis and had non-small-cell lung cancer with tumors smaller than 4 cm. Of the patients, 76.623 underwent surgery and 8.216 received SBRT. Mortality at 1 month and 3 months was higher in the surgical arm. SBRT was shown to be an effective alternative to surgery. Although long-term results are awaited, it can be considered an option for patients unsuitable for surgery.

4. Alectinib Received FDA Approval for First-Line Treatment of ALK-Positive Lung Cancer That Has Spread (November 2017)

ALK positivity occurs in 5% of non-small-cell lung cancers. It had received FDA approval and entered use in patients whose disease progressed during first-line crizotinib.

In a study comparing it with crizotinib in untreated ALK-positive lung cancer, it extended the time to disease progression by an additional 15 months and reduced death and disease progression by an additional 53%. Based on this study, alectinib (Alecensa) received FDA approval and took its place in first-line treatment.

5. Dabrafenib and Trametinib Demonstrated Success in BRAF-Positive Stage 4 Lung Cancer (September 2017)

BRAF mutation is common in the skin cancer malignant melanoma. Combined use of two drugs developed against this genetic change has been highly successful. The same change occurs in 1-2% of non-small-cell lung cancers. A study evaluating this combination in lung cancer enrolled previously untreated patients with metastatic non-small-cell lung cancer carrying a BRAF V600 mutation. Treatment was the BRAF inhibitor dabrafenib (Tafinlar) and the MEK inhibitor trametinib (Mekinist). Disease control lasted 10.9 months, and the treatment's cancer control rate was 75%.

As genetic changes driving lung cancer are identified, targeted drugs developed against them will contribute greatly to our patients' treatment.

6. Osimertinib Demonstrated Efficacy in EGFR-Positive Stage 4 Lung Cancer (September 2017)

The first options for EGFR-positive lung cancer were the older tyrosine kinase inhibitors erlotinib (Tarceva) and gefitinib (Iressa). When resistance developed, another genetic test was performed, and if this genetic test identified a T790M mutation in EGFR, osimertinib (Tagrisso) was used. A study found that first-line osimertinib provided superior survival compared with erlotinib or gefitinib.

7. How Long Should We Continue Immunotherapy in Stage 4 Lung Cancer? (September 2017)

Immunotherapies have demonstrated efficacy in non-small-cell lung cancer, but clear data on treatment duration are lacking. A study seeking to determine this stopped treatment in some patients whose disease had not progressed under 1 year of nivolumab (Opdivo), while others continued. Time to worsening was longer with continued treatment, but overall survival did not differ between groups. Unless supported by longer follow-up and new studies, we believe continuing treatment is more appropriate in patients benefiting from immunotherapy.

8. FDA Approval for Broad Genetic Testing in Advanced Organ Cancers (November 2017)

More comprehensive next-generation DNA sequencing offers hope for identifying patients with rare but treatable targets and accelerating molecular oncology research. The genetic test Foundation One CDx can detect, in 324 genes known to be associated with cancer, mutations . These mutations are particularly common in lung, colon, breast, ovarian cancer and skin melanoma.

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