“On March 18, 2019, the U.S. Food and Drug Administration (FDA) approved atezolizumab (Tecentriq) in combination with carboplatin and etoposide for the first-line treatment of adult patients with extensive-stage small cell lung cancer.
Approval was based on the IMpower133 study, a randomized (1:1), multicenter, double-blind, placebo-controlled trial in 403 patients with extensive-stage small cell lung cancer who received no prior chemotherapy for extensive stage disease and had ECOG performance status 0 or 1.”
“Patients with unresectable, or inoperable, lung cancer are often given a dismal prognosis, with low rates of survival beyond a few years. Researchers exploring combination therapies have recently discovered improved survival rates by up to one year when patients treated with a newly formulated chemotherapy regimen are also given radiation therapy.
“A group of patients with metastatic non-small-cell lung cancer (mNSCLC) who had already been enrolled in a clinical trial were given radiation therapy, in addition to their treatment with a novel chemotherapy formulation, mPEBev, which was designed for its immune-modulating and anti-angiogenic effects. The mPEBev regimen is composed of fractionated cisplatin, oral etoposide, and bevacizumab, a monoclonal antibody that inhibits blood vessel growth in the tumor. Treatments were administered metronomically, spaced out in the safest possible doses to reduce side-effects and toxicity.”
“Improvements in OS, but not PFS, indicate that maintenance treatment with pembrolizumab may benefit a subset of patients with small cell lung cancer, and biomarkers are needed to identify individuals in whom pembrolizumab may be effective, according to findings presented at the ASCO Annual Meeting.
” ‘The standard of care for these patients – 4 to 6 cycles of platinum plus etoposide – has not changed in the United States in the last 30 years,’ Shirish Gadgeel, MD, of the Karmanos Cancer Institute in Detroit, said during a presentation. ‘Despite a high response rate with this therapy, overall outcomes for these patients are quite poor. There is a need to identify other agents that can provide benefit in these patients.’ ”
“Adding palifosfamide to carboplatin and etoposide failed to improve survival over the latter two agents alone in patients with extensive stage (ES) small-cell lung cancer (SCLC), according to a new study.
” ‘Platinum doublet chemotherapy has been the standard of care first-line regimen in patients with ES SCLC for the last 3 decades,’ wrote study authors led by Shadia I. Jalal, MD, of the Indiana University Melvin and Bren Simon Cancer Center in Indianapolis. ‘Unfortunately, disease relapse occurs in all patients, and second-line chemotherapy options lead to short responses. Novel first-line therapies continue to be urgently needed.’ ”
Any type of advanced lung cancer is bad news, but a diagnosis of small cell lung cancer (SCLC) is a particularly grim one to receive. About 30 years have passed since any new treatments for SCLC were developed, and patients’ responses to standard chemotherapy with etoposide and cisplatin are short-lived. Hopefully, this will change soon.
Editor’s note: This article discusses the results of a laboratory study done in mice and human cells. The drug has not yet been tested in lung cancer patients, although it is currently being tested in patients with other types of cancer.
“An existing drug may help some patients with non-small-cell lung cancer (NSCLC) whose tumors have become resistant to chemotherapy, finds a study from Boston Children’s Hospital and the Dana-Farber Cancer Institute (DFCI). The findings, in human cancer cells and in mice, suggest a window of vulnerability in NSCLC, the leading cause of cancer-related deaths worldwide.1 The work was published online today by the journal Nature.
“NSCLC is a highly genetically complex cancer with many different subtypes, each bearing different mutations. In two common subtypes that do not respond to standard chemotherapy—tumors with BRG1 or EGFR mutations—the researchers increased the effectiveness of etoposide, a common chemotherapy agent, by adding an epigenetic therapy already in clinical testing.
“Conversely, when the same epigenetic therapy (inhibition of an enzyme known as EZH2) was added to certain tumors without BRG1 and EGFR mutations, the tumors become more resistant to chemotherapy. Together, the findings advance the idea of individualized, ‘precision medicine’ in cancer, incorporating epigenetic therapy guided by tumor genetic testing.”
The gist: A recent study showed similar survival rates for two different drug combinations for stage III non-small cell lung cancer (NSCLC). The study compared EP (treatment with the drugs etoposide and cisplatin) with CP (carboplatin plus paclitaxel). Both drug combinations were given along with radiation therapy. The study showed that EP might cause worse side effects, but the researchers say that more research will be needed to determine whether either EP or CP is better for treating stage III NSCLC.
“An analysis of Veterans Health Administration patients showed that etoposide/cisplatin (EP) and carboplatin/paclitaxel (CP) yielded similar overall survival along with radiotherapy in patients with stage III non–small-cell lung cancer (NSCLC), but EP was associated with increased morbidity. Prospective studies are still needed to determine the optimal treatment in these patients.
“ ‘There is considerable concern that CP, although better tolerated than EP, may be inferior in terms of disease control,’ wrote study authors led by Rafael Santana-Davila, MD, of the University of Washington in Seattle. To better understand the differences between the regimens, researchers looked into outcomes of patients in the VA Central Cancer Registry.
“The study included a total of 1,842 patients treated with concurrent radiotherapy and either EP or CP between 2001 and 2010. EP was used in 27% of the full cohort…
“Though the similar survival and increased morbidity with EP suggest CP may be the preferred treatment, Santana-Davila said in an email that “the study is not able to provide a firm recommendation. It has many limitations, and although we tried to adjust for confounders with several techniques, it is still a retrospective study.”
“Those limitations include a lack of data on dose or duration of therapy, and there were treatment differences such as an increased rate of consolidation chemotherapy with CP patients. The reliance on coded administrative data to identify toxicities is also less reliable than methods used in clinical trials.
“ ‘The only way we could provide firm recommendations would be with a phase III randomized trial,’ Santana-Davila said. In the meantime, the authors concluded that these results may simply help guide treatment decisions in stage III NSCLC patients.”
The gist: Recent research comparing two drug combinations for stage III non-small cell lung cancer (NSCLC) suggests that the drug combo etoposide/cisplatin does not help people live longer than carboplatin/paclitaxel does, and it also may result in more side effects. Both drug combos are taken alongside radiation treatment.
“In an analysis of Veterans Health Administration data reported in the Journal of Clinical Oncology, Santana-Davila et al found that etoposide/cisplatin resulted in no overall survival difference but greater morbidity compared with carboplatin/paclitaxel used concurrently with radiotherapy in patients with stage III non–small cell lung cancer (NSCLC).
“The analysis involved 1,842 patients treated with etoposide/cisplatin (n = 499) or carboplatin/paclitaxel (n = 1,343) between 2001 and 2010. In a Cox proportional hazard model, age (hazard ratio [HR] = 1.08, P = .0258), percentage weight loss (HR = 1.04, P < .0001), baseline anemia (HR = 1.19, P = .0064), hypoalbuminemia (HR = 1.29; 95% confidence interval [CI] = 1.14–1.46; P < .001), and treatment era (HR = 0.89 for 2005-2007 and 0.83 for 2008-2010 vs 2001-2004, P = .028) were independently associated with overall survival, whereas chemotherapy regimen (median overall survival = 17.3 months for etoposide/cisplatin vs 14.6 months for carboplatin/paclitaxel, HR = 0.97, P = .6327), stage (HR = 1.08, P = .185, for IIIB vs IIIA), and National Cancer Institute combined index score (HR = 1.17, P = .0503) were not associated with survival…
“The investigators concluded: ‘After accounting for prognostic variables, patients treated with [etoposide/cisplatin vs carboplatin/paclitaxel] had similar overall survival, but [etoposide/cisplatin] was associated with increased morbidity.’ ”
“Cisplatin, etoposide, and irinotecan outperformed topotecan as second-line chemotherapy in patients with sensitive relapsed small-cell lung cancer (SCLC) in a Japanese trial, though there was substantially increased toxicity with the regimen.
“ ‘Topotecan is the only drug approved in the United States and the European Union for relapsed SCLC,’ said Koichi Goto, MD, PhD, of the National Cancer Center Hospital East in Chiba, Japan. He presented results of the new trial at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. Sensitive relapse refers to cancers that respond to initial chemotherapy and relapse more than 3 months after completion of that therapy, while refractory cancers do not respond initially or relapse within that 3 month window.”
Editor’s note: This story is about a clinical trial with volunteer patients to test a new treatment for small cell lung cancer (SCLC). The new treatment is specifically for people with SCLC who were treated with chemotherapy successfully, but whose cancer returned more than 3 months after chemo—this is known as “sensitive relapsed SCLC.” The new treatment combines three chemo drugs: cisplatin, etoposide, and irinotecan. In the clinical trial, some patients took the chemo combo and some were treated with the chemo drug topotecan, which is a standard treatment for the condition. Patients who took the new treatment lived longer, but they had more toxic side effects than the patients who took topotecan.