Lurbinectedin Proves Effective as Second-line Therapy Option for Patients With Metastatic SCLC

Lung cancer remains the second most common cancer in both men and women in the United States with an estimated 235,760 adults (119,100 men and 116,660 women)¹ expected to be diagnosed in 2021. There are two main types of lung cancer including the more prevalent non-small cell lung cancer and small cell lung cancer (SCLC), which tends to grow and spread more aggressively.

According to the American Society of Clinical Oncology, approximately only 13%¹ of people are diagnosed with SCLC, which is sometimes called oat cell cancer.² Due to SCLC’s faster growth, it tends to respond well to chemotherapy and radiation therapy,² however, its aggressive nature also increases likelihood of recurrence. About 70% of people with SCLC will have cancer that has already spread at the time they are diagnosed.²

Because lung cancer is common, the American Cancer Society recommends yearly screening with low-dose CAT scan or CT scan (LDCT) for at-risk, eligible populations. Their current recommendations³ include people who are aged 55 years to 74-years old, in fairly good health, and meet a variety of conditions: (1) are current smokers who have quit in the past 15 years; (2) have at least a 30-pack-a-year smoking history; (3) have received counseling to quit smoking if they are currently smokers; (4) have been advised by a physician about the benefits, limits, and harms of LDCT scans; and (5) have a facility available to them for screening.

Even with early screening and detection, more people die from lung cancer in the US than from any other type of cancer, making finding beneficial treatments, especially for those with recurring SCLC, all the more important.

Initial Treatment and Next Steps

Typical systemic therapies used to treat SCLC include chemotherapy and immunotherapy, or a combination.⁴ These can also be given as part of a treatment plan that includes radiation and/or surgery.

Drugs currently approved by the FDA for the treatment SCLC include⁵ Afinitor (everolimus), Atezolizumab, doxorubicin hydrochloride, Durvalumab, Etopophos (etoposide phosphate), Etoposide, etoposide phosphate, Everolimus, Hycamtin (topotecan hydrochloride), Imfinzi (durvalumab), Lurbinectedin, methotrexate sodium, Nivolumab, Opdivo (nivolumab), Tecentriq (atezolizumab), Topotecan Hydrochloride, Trexall (methotrexate sodium), and Zepzelca (lurbinectedin).

In patients who develop metastatic SCLC, treatment often includes combinations of several drugs in addition to radiation. Patients with metastatic SCLC will often also need palliative care to relieve symptoms and side effects.⁴

If a patient relapses after a treatment regimen, a new cycle of testing is conducted to determine if the same treatment regimen and medication combinations are effective. Patients and care teams at this point have limited treatment options but new medications and therapies are being studied and developed.

New Treatment Options and Recommendations

New second-line therapy options have recently been approved and show promise for patients with metastatic SCLC.

Lurbinectedin therapy received FDA accelerated approval on June 15, 2021 for adult patients with metastatic SCLC and those on or after platinum-based chemotherapy.⁶

Under the NCCN Clinical Practice Guidelines in Oncology, lurbinectedin is a Category 2A recommended treatment option for patients who relapse ≤6 months or >6 months following first-line platinum-based chemotherapy.⁷

The approval for lurbinectedin was based on evidence from the RECIST clinical trial consisting of 105 adults with metastatic SCLC. All patients had SCLC that had progressed on or after previous platinum-based therapy and received lurbinectedin infusions once every 3 weeks until tumor progression or intolerable adverse effects. The benefit was measured in the overall response rate, percent of patients achieving complete or partial tumor shrinkage, and by measuring duration of response (DOR). Of the 105 patients with SCLC receiving lurbinectedin, 35% (95% CI, 26%-45%) experienced partial tumor shrinkage, with a median DOR of 5.3 months (95% CI, 4.1-6.4). The ORR was 30% (95% CI, 22%-40%) with a median DOR of 5.1 months (95% CI, 4.9-6.4).^6-7

The most common adverse effects are decreased blood cell counts, tiredness, increased creatinine, alanine transaminase, blood glucose, and nausea.^6-7

Lurbinectedin is administered by an intravenous (IV) infusion delivering a 3.2 mg/m² dose over the course of one hour, repeated every 21 days until disease progression or unacceptable toxicity. Lurbinectedin can be administered in an outpatient clinic and its dosing schedule of a single infusion every 21 days may result in less time a patient receives treatment in the clinic or hospital compared to other options.⁸

"Small cell lung cancer is a disease with limited treatment options, and the approval of [lurbinectedin] represents an important advance for patients whose metastatic SCLC has progressed on or after platinum-based therapy," said Bruce Cozadd, chairman and CEO of Jazz Pharmaceuticals in a press release.⁸ "While patients may initially respond to traditional chemotherapy, they often experience an aggressive recurrence that is historically resistant to treatment."

"Seeing first-hand the aggressive nature of SCLC and knowing that the large majority of those diagnosed will experience relapse, I am excited to see an effective new treatment demonstrating durable responses," said William Jeffrey Petty, MD, oncology specialist, Wake Forest Baptist Health, in a press release.⁸ "For doctors, patients and their families, [lurbinectedin] is an important and much-needed addition to the treatment landscape for relapsing SCLC."

References:

1. Lung cancer—small cell: statistics. Updated January 2021. Accessed April 6, 2021. https://www.cancer.net/cancer-types/lung-cancer-small-cell/statistics
2. American Cancer Society. What Is lung cancer? Updated October 1, 2019. Accessed April 6, 2021. https://www.cancer.org/cancer/lung-cancer/about/what-is.html
3. American Cancer Society. Can lung cancer be found early? Updated October 1, 2019. Accessed April 6, 2021https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/detection.html
4. Lung cancer–small cell: types of treatment. https://www.cancer.net/cancer-types/lung-cancer-small-cell/types-treatment
5.  National Cancer Institute. Drugs approved for lung cancer. Updated March 12, 2021. Accessed April 6, 2021. https://www.cancer.gov/about-cancer/treatment/drugs/lung
6. FDA grants accelerated approval to lurbinectedin for metastatic small cell lung cancer. US Food & Drug Administration. June 16, 2020. Accessed April 6, 2021. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-lurbinectedin-metastatic-small-cell-lung-cancer
7. ZEPZELCA (lurbinectedin). Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc.
8. Jazz Pharmaceuticals announces US FDA accelerated approval of Zepzelca (lurbinectedin) for the treatment of metastatic small cell lung cancer. Jazz Pharmaceuticals. June 15, 2020. Accessed April 6, 2021. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-us-fda-accelerated-approval