Popular Treatment Methods
Recently medical professionals introduced immunotherapy with high expectations to treat small cell lung cancer. The genome sequence unraveling also revealed possible targets as biomarkers in treating future small cell lung cancer patients. Many patients benefit from immunotherapy and targeted therapy with an improved prognosis.
Note: The radiotherapy, immunotherapy, and targeted treatment options are only for a few people. Progressing treatment options are vital to treating small cell lung cancer, so the Exome sequencing came into existence. Exome sequencing for identifying targetable biomarkers selects patients benefitting from various therapies.
Small cell lung cancer starts from the neuroendocrine precursor cells. They characterize it with early metastasis and growth, with up to 70% of patients presenting metastasized disease. Around 10 to 25% are brain metastases patients, with around 40 -50% developing these during disease. The first line of treating metastatic small cell lung cancer is etoposide and platinum.
However, many patients relapse in the first treatment year because of poor survival. Various agents or third drug addition didn’t provide significant improvements and outcomes.
Even in patients who didn’t have metastases detected, the cure rate was low. Thus, there is an unmet therapy requirement to improve small cell lung cancer patients’ survival rate. The guidelines haven’t been updated since 2013.
Let’s address experts’ recent breakthroughs in small cell lung cancer, including surgery, staging, systematic treatment, and radiotherapy.
Immunotherapy Encourages Development Of Fuel Drug
In reviewing data from different studies, researchers called for attention to baseline patient characteristics while focusing on PD-L1 role in outcomes. Chemotherapy-naive patients at an advanced stage without targetable mutations can find pathways with PD-L1 expression.
Many things are coming into play for immunotherapy, which has a certain effect. We know that the tumor cells in neoantigen interacted with T cells. What’s new is the entire checkpoint idea.
The study begins with a phase 3 KEYNOTE-24 trial (NCT0214738). Researchers pointed out pembrolizumab efficacy versus platinum-doublet chemotherapy in non-small lung cancer metastatic (NSCLC) and PD-L1 with a 50% tumor proportion score. Doctors administered Pembrolizumab at 200 mg dose intravenously after every three weeks. They did this for two years and provided chemotherapy for 4 to 6 cycles. The patients progressing after chemotherapy can crossover the pembrolizumab arm.
Patients with stage 4 untreated NSCLC should have one or less ECOG performance to become eligible for the trial. They couldn’t activate mutations of ALK and EGFR translocations. Medical professionals didn’t consider the untreated brain metastasis cases or active autoimmune diseases with systemic therapy.
There was a study of a random group of eligible patients (N=305) in two groups, chemotherapy and pembrolizumab arms. In pembrolizumab group patients (n = 154) got OS median of 26.3 months (95% Cl, 18.3 to 40.4) compared to the 13.4 chemotherapy group months (95% Cl, 9.4 – 18.3.) OS rates for five years were 31.9% vs. 16.3%.
Here they got a median PFS of 7.7 months time (95% CI, 6.1 – 10.2) vs 5.5 months (95% CI, 4.2 to 6.2), respectively (HR 0.50; 95% CI, 0.39 to 0.65). Three-year rates for PFS were 22.8* and 4.1%, respectively. ORR was 46.1% in the pembrolizumab arm with 4.5% complete response (CR) in comparison to 31.1% and no chemotherapy group CRs. Now, let’s talk about the outcomes of the Pembrolizumab Phase-III.
Pembrolizumab- Phase III
Investigators started the phase 3 KEYNOTE-042 study (NCT02220894) to distill pembrolizumab efficiency in a particular group of patients. Pembrolizumab dose administration was at 200 mg every 3 weeks for up to 35 cycles (n=637) vs the standard-of-care (SOC) platinum-based chemotherapy for around 6 cycles (n = 637). Patients should have 1% PD-L1 TPS or greater with 0 or 1 performance status for the particular trial. The primary endpoint was OS in patients with PD-L1 TPS of around 50% with at least 20% and the least 1%.
Patients with pembrolizumab with PD-L1 TPS of at least 50% (n=73) had 20 months median OS (95% Cl, 15.9 – 24.2) while comparing to 12.2 months (95% Cl, 10.4 to 14.6) in the chemotherapy group of 85 patients (HR, 0.68; 95% Cl, 0.57 to 0.82). In chemotherapy (n = 84) and pembrolizumab (n = 75) subgroups the median OS was for patients with PD-L1 TPS of minimum 20% was 13 months (95% Cl, 11.6 to 15.3) and 18.0 (95% Cl, 15.5 to 21.5), respectively (HR ,0.75; 95% Cl, 0.64 – 0.88).
Patients with PD-L1 TPS has at least 1% and the median OS was 16.4 months (95% Cl, 14.0 – 19.6) in 79 patient pembrolizumab cohort vs 12.1 months (95% Cl, 11.3 to 13.3) in 87 patient chemotherapy cohort (HR, 0.80; 95% Cl, 0.71 to 0.90).
Other than pembrolizumab, scientists also pointed to data from other key trials with agents in targeted therapy combinations.
Now, the primary and the most recommended therapy comes to treat small cell lung cancer. Chemotherapy is one of the most popular cancer treatment techniques used for almost every cancer type. The therapy is categorized into two parts:
Recently, a lot of hype has been there around metronomic chemotherapy. A metronomic chemotherapy regimen of irinotecan, etoposide, and cisplatin comparison is there with single-agent topotecan in Japanese patients with recurrent sensitive small cell lung cancer. The study enrolled 180 patients with randomized patients of 1:1 to metronomic regimen or control. OS in patients with a three-drug metronomic regimen was longer for topotecan treatment alone (18.2 months vs. 12.5 months, HR 0.67, P = 0.0079). The positive outcome represents a vital breakthrough in second-line small cell lung cancer treatment. However, you cannot ignore the three-drug metronomic regimen toxicity. We are yet to explore whether metronomic chemotherapy can be a second line of treatment or not.
Lurbinectedin is an RNA polymerase II inhibitor, and its hyperactivation is common in SCLA. Excessive tumor cell transcription occurs due to this inhibitor. Inhibition through lurbinectedin decreases tumor cell proliferation primarily after inhibiting mitosis. United States Food and Drug Administration (FDA) provided lurbinectedin (PM1183) as orphan drug status to treat small cell lung cancer.
After the phase II multicenter basket study (NCT02454972), it got this designation for assessing efficacy in 68% of recurrent small cell lung cancer patients. After evaluating the efficiency of 61 patients, their ORR was 39.3%, and seven patients got stable disease for up to 4 months after treatment. The overall clinical benefit rate was around 50.8%, the disease control rate was 73.8%, and the median OS was 11.8 months.
Myelosuppression was the most adverse event: 44% neutropenia grade (G) ¾, 8% thrombocytopenia, 12% febrile neutropenia. Among these adverse events, around eight patients got dose delays because of neutropenia G2-4. Ten patients had reduced doses because of neutropenia G4.
An ongoing phase 3 topotecan vs. lurbinectedin plus doxorubicin completed accrual and must offer additional evidence supporting this agent’s efficacy in small cell lung cancer.
The Scope Of These Treatment Options
Immunotherapy has proven a promising treatment option for small cell lung cancer treatment breakthroughs in recent years. According to a study, nivolumab got approval from the Food and Drug Administration (FDA) to treat recurrent small cell lung cancer. It made it the first FDA-approved third-line treatment option for small cell lung cancer. Atezolizumab with chemotherapy is the first line of treatment that demonstrated improved efficacy in the study of IMpower133.
It is the first study in phase III to improve OS in up to 30 years to treat extensive-stage small cell lung cancer. Besides immunotherapy as a primary small-cell lung cancer treatment breakthrough, many challenges exist. There are limitations to its efficacy, and it is helpful for only some patients. It’s important to find predictive biomarkers to select patient subgroups that can benefit from this treatment method.
Although targeted therapy dramatically changes the approach to treating NSCLC, similar non-materialized breakthroughs exist for small cell lung cancer. However, these initial outcomes need further validation to become a common treatment choice for small cell lung cancer patients.
With the clinical studies and emerging drugs mentioned above, we concluded there are still many treatment combinations and drugs in the early clinical development stage or conducted in preclinical studies. To know more about the most promising treatment options for small cell lung cancer, you can consult the highly qualified medical specialists at University Cancer Centers. We are a team of dedicated and striving professionals backed by many years of extensive research and high-end technology to retrieve the best medical solutions for your health concerns.