Stage IV lung cancer survivor: Targeted therapy and surgery left me cancer-free
Retrospective Study Shows Bevacizumab Biosimilar Efficacy In NSCLC
Bevacizumab biosimilars have the potential to expand access and reduce costs without compromising patient outcomes in advanced non–small cell lung cancer (NSCLC)
Bevacizumab biosimilars were found to be as effective as the reference product in terms of progression-free survival (PFS) when combined with chemotherapy or epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in patients with advanced non–small cell lung cancer (NSCLC), according to a retrospective study.1
This study was conducted to address the limited real-world data on the clinical efficacy of bevacizumab biosimilars in advanced NSCLC, a leading cause of cancer-related deaths globally, and its findings highlight that bevacizumab biosimilars are effective treatment options comparable to the reference product (Avastin), expanding access and reducing costs without compromising patient outcomes.
Lung cancer remains the leading cause of cancer-related deaths worldwide. Lung cancer is primarily classified into two types, with NSCLC accounting for 80% to 85% of cases and small cell lung cancer making up 10% to 15%Image credit: mi_viri - stock.Adobe.Com
Lung cancer remains the leading cause of cancer-related deaths worldwide. Lung cancer is primarily classified into 2 types, with NSCLC accounting for 80% to 85% of cases and small cell lung cancer making up 10% to 15%.2 While treatments like bevacizumab have shown improved outcomes in advanced NSCLC, real-world data on the efficacy of bevacizumab biosimilars in this setting are limited despite their potential to reduce costs and expand access to care.
The study retrospectively analyzed patients with stage IV non-squamous NSCLC treated at Taichung Veterans General Hospital, focusing on those receiving first-line combination therapy with bevacizumab (reference product or biosimilar). Patient inclusion required at least 3 cycles of anti-angiogenic therapy, with exclusions for mixed cancer types or second-line treatments.
From January 2020 to July 2022, 79 patients were enrolled in the study, including 59 treated with chemotherapy (CT) and 20 with TKIs, in combination with either the bevacizumab reference product (RP) or its biosimilar (BB).
These patients were divided into 4 subgroups:
The median age of the overall cohort was 60.4 years, with 60.8% being female, 64.6% never-smokers, and 86.1% having an ECOG performance status (PS) of 0 to 1. Nearly half of the patients (44.3%) had brain metastases, and 49.4% presented with malignant pleural effusion. There were no significant differences in baseline demographics or disease characteristics between the biosimilar and RP groups.
In the CT cohort, the median age was 61.5 years, with 61% female and 62.7% never-smokers. Most patients (62.7%) had stage 4B disease, and 71.2% received cisplatin-based regimens. The median PFS was 8.9 months for CT-BB and 6.9 months for CT-RP, with no significant difference (P = .255). The CT-BB group had an objective response rate (ORR) of 34.8% and a disease control rate (DCR) of 78.3%, similar to 41.2% ORR and 75.8% DCR in the CT-RP group. Tumor stage was the only variable significantly predicting PFS in this cohort, with patients at stage IVB facing higher risks of progression. The choice of bevacizumab product (BB or RP) did not significantly affect outcomes.
In the TKI cohort, the median age was 56.3 years, with 60% female and 70% never-smokers. Most patients (90%) had stage IVB disease. The median PFS was 13.6 months for TKI-BB and 18.4 months for TKI-RP, with no significant difference (P = .363). The TKI-BB subgroup achieved an ORR of 80% and a DCR of 90%, comparable to 71.4% ORR and 100% DCR in the TKI-RP subgroup. No predictors of PFS were identified in this group.
Adverse events were comparable between BB and RP subgroups. In the CT cohort, hypertension was reported in 52.5% and proteinuria in 39% of patients, with similar rates between CT-BB and CT-RP. Three cases of thrombosis were observed: 1 pulmonary embolism in each subgroup and one deep vein thrombosis in CT-RP. In the TKI cohort, hypertension occurred in 50% and proteinuria in 45% of patients, with no hemorrhage or thrombosis reported. Overall, the study found no significant differences in efficacy or safety profiles between the bevacizumab biosimilar and the reference product in either the CT or TKI cohorts.
The study's limitations include its retrospective design, small sample size, limited generalizability due to a single-center, Taiwanese-only patient population, lack of standardized criteria for choosing between reference product and biosimilar, and inability to analyze the 15 mg/kg bevacizumab dosage.
"With patents expiring, the development of biosimilars not only ensures similar clinical treatment efficacy but also has the potential to reduce healthcare expenditure…." the authors concluded. "Biosimilars help to reduce medical expenses and also expand access to treatment for patients with cancer…. Therefore, we believe that opting for the lower dosage did not compromise our treatment outcomes."
References
1. Ou W-F, Hsu K-H, Tseng J-S, et al. Real-world clinical efficacy of bevacizumab biosimilar in patients with advanced non-small-cell lung cancer. Ther Adv Med Oncol. Published online October 17, 2024. Doi:10.1177/17588359241290718
2. Key statistics for lung cancer. American Cancer Society. Updated January 29, 2024. Accessed November 26, 2024. Https://www.Cancer.Org/cancer/types/lung-cancer/about/key-statistics.Html#:~:text=Most%20lung%20cancer%20statistics%20include,%25%20to%2085%25%20are%20NSCLC
Tiragolumab Combo In PD-L1 High NSCLC Misses Overall Survival Endpoint
A phase 3 trial evaluating tiragolumab in combination with Tecentriq® (atezolizumab) in adults with PD-L1 high locally advanced or metastatic non-small cell lung cancer (NSCLC) did not meet its primary endpoint of overall survival (OS), according to Genentech.
Tiragolumab is a novel immune checkpoint inhibitor that binds to TIGIT, a protein receptor on immune cells, which suppresses the immune response to cancer. The Company believes that combining tiragolumab with atezolizumab, a PD-L1 blocking antibody, will increase anti-tumor activity by enhancing the body's immune response to cancer cells.
The global, randomized, double-blinded phase 3 SKYSCRAPER-01 study (ClinicalTrials.Gov Identifier: NCT04294810) included 534 study participants with previously untreated, locally advanced unresectable or metastatic PD-L1 selected NSCLC. Participants were randomly assigned 1:1 to receive tiragolumab with atezolizumab or placebo with atezolizumab every 3 weeks until disease progression, loss of clinical benefit, or unacceptable toxicity.
Findings showed the study did not reach the primary endpoint of OS at the final analysis. Previous interim results showed tiragolumab plus atezolizumab also did not meet the other primary endpoint of progression-free survival.
The overall safety profile remained consistent even with extended follow up. No new safety signals were identified.
According to the Company, detailed results will be presented at a medical meeting in 2025.
References:
Genentech reports update on phase 3 SKYSCRAPER-01 study results. News release. Genentech. November 26, 2024. Https://www.Businesswire.Com/news/home/20241125394901/en/Genentech-Reports-Update-on-Phase-III-SKYSCRAPER-01-Study-Results.
Radiotherapy And EGFR-TKIs May Improve Treatment Outcomes In Lung Cancer
CURE® spoke with a lung cancer treatment expert about study findings showing survival benefits with the addition of radiotherapy to TKI treatment.
A lung cancer treatment expert discusses study findings in non–small cell lung cancer.
EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment given with concurrent thoracic radiotherapy (TRT) treatment was shown to improve progression-free survival (PFS) in patients with EGFR-mutated oligo-organ metastatic non–small cell lung cancer (NSCLC), with acceptable and tolerable treatment-related adverse effects, according to phase 3 trial data.
Researchers published findings from their multicenter phase 3 clinical trial in the Journal of Clinical Oncology, which enrolled 118 patients in China between April 14, 2016, and Feb. 25, 2022.
The median PFS was 10.6 months among patients treated with EGFR-TKIs versus 17.1 months for patients treated with EGFR-TKIs and TRT. The median overall survival (OS) was 26.2 months and 34.4 months, respectively, in these treatment groups. Rates of treatment-related adverse effects were 5.1% and 11.9%, respectively.
CURE® spoke with Dr. Coral Olazagasti, an assistant professor at the Sylvester Cancer Center, University of Miami and a member of the CURE® advisory board, about this study and its findings via email.
CURE: For patients with lung cancer, what do you think should be the big takeaway from these findings?Olazagasti: The key takeaway for patients with EGFR-mutated advanced NSCLC is that [treatment with] concurrent lung radiation therapy and TKIs leads to longer survival benefits compared with TKIs alone, particularly in those with oligo-organ metastatic disease [where the cancer has spread to a limited number of organs]. This approach leverages the synergy between targeted therapy and localized radiation to manage metastases more effectively, potentially improving overall outcomes. It's an important consideration for personalizing treatment plans in this patient population.
GlossaryTyrosine kinase inhibitors: A type of targeted therapy designed to stop cancer cells from growing.
Thoracic radiotherapy: Treatment using high-energy radiation in the chest, lungs and surrounding region.
Progression-free survival (PFS): The time a patient lives without their disease spreading or worsening
Overall survival (OS): The time a patient lives, regardless of disease status.
Was there anything about this study and its findings that you found particularly surprising?The study's findings of enhanced efficacy in combining TKIs with radiation therapy, particularly among women, older patients, and those with brain metastases, are intriguing. These observations suggest that certain patient subgroups may derive greater benefit from combined modality treatments, highlighting the need for personalized therapeutic approaches.
However, the referenced study utilized [Conmana (icotinib)], a first-generation TKI. However, current standard care in the United States has shifted towards third-generation TKIs, such as [Tagrisso (osimertinib)], due to superior efficacy. Notably, [Tagrisso] has demonstrated a median OS of 38.6 months in patients with EGFRexon 19 deletions or exon 21 L858R mutations, surpassing the 26.2 months observed with [Conmana]. This significant difference underscores the importance of evaluating the applicability of older regimens in today's clinical practice. The potential benefits of combining radiation therapy with TKIs warrant further investigation, especially concerning modern TKIs like [Tagrisso]. Assessing the role of consolidation radiation therapy alongside current standard-of-care TKIs could provide valuable insights into optimizing treatment strategies for patients with oligo-organ metastatic disease.
Recent developments, such as the approval of the combination of [Rybrevant (amivantamab)] with [Lacluze (Lazertinib)] as a first-line therapy for EGFR-positive advanced NSCLC, have shown promising results. The MARIPOSA trial reported a 7.1-month PFS benefit over [Tagrisso], indicating a potential shift in first-line treatment approaches.
What is oligo-organ metastatic NSCLC?In the referenced study, oligo-organ metastasis was defined as the presence of metastatic disease in three or fewer synchronous organs in patients with advanced NSCLC. This categorization focuses on patients with a limited burden of metastatic disease, which may be more amenable to aggressive local and systemic therapies, such as the combination of radiation and TKIs.
This study targeted a very specific patient population. What implications do these findings potentially have for a broader patient population?The findings of this study raise important considerations when evaluating their applicability to broader populations, particularly in regions outside of China, where the study was conducted. Differences in patient demographics, genetic variations and healthcare systems can significantly impact the generalizability of the results.
The baseline characteristics of the study population also highlight potential biases that may have influenced the results. The average age of participants was less than 60 years, which is younger than the typical NSCLC population in many Western countries, where patients are often older and may have additional comorbidities. Furthermore, the combination therapy arm predominantly included patients with a lower metastatic burden (one or fewer metastatic organs) compared to the TKI-alone group, where most patients had involvement in two organs. This imbalance could have favored the combination therapy arm, raising questions about whether similar benefits would be observed in a population with a higher metastatic burden or more advanced disease.
Another important consideration is the higher incidence of grade 3 [severe] or 4 [life-threatening] treatment-related adverse events in the combination therapy arm [11.9% versus 5.1% in the TKI-alone group]. While the combination therapy showed promising efficacy, the increased toxicity could limit its applicability to older or comorbid patients who may not tolerate such aggressive treatment regimens. The toxicity profile is a critical factor in determining the feasibility of incorporating combination therapy into standard practice. Additionally, the study's use of [Conmana], a first-generation TKI, as the treatment backbone limits its relevance in the context of modern care.
To ensure applicability to a broader and more diverse patient population, future trials should include patients of varying ages, comorbidities, ethnicities and metastatic burdens. Subgroup analyses focusing on these factors, along with careful monitoring of toxicity, are crucial to determine which patients are most likely to benefit from combination therapy. Such studies will provide clearer insights into the feasibility and potential benefits of integrating radiation therapy with modern TKIs in contemporary clinical practice.
Reference: "Thoracic Radiotherapy Improves the Survival in Patients With EGFR-Mutated Oligo-Organ Metastatic Non–Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitors: A Multicenter, Randomized, Controlled, Phase III Trial" by Dr. Hongfu Sun, Journal of Clinical Oncology.
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