Oncology

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Index:

Evaluation of Atezolizumab
Evaluation of Low-dose Pembrolizumab therapy in NSCLC patients
Pembrolizumab Monotherapy for Advanced NSCLC

Capsule Summary

Evaluation of Atezolizumab Monotherapy in Metastatic NSCLC patients

The Advent of immune checkpoint inhibitors has created a paradigm shift for the treatment of numerous malignancies. Inhibitors targeting Programmed Cell Death 1 (PD- 1) receptor and its ligand PD-L1, alone or in combination with chemotherapy drugs represent the new standard of treatment for difficult to treat malignancies such as non- small cell lung carcinoma (NSCLC).
A recent study by Herbst et al. evaluated the safety and efficacy of the anti-programmed death ligand-1 (PD-L1) monoclonal antibody, Atezolizumab, in metastatic NSCLC patients. Atezolizumab is marketed as TECENTRIQ by Genentech. Following sections provide a summary of the key findings presented in the study.

Study Objective

To evaluate the safety and efficacy of Atezolizumab as the first line treatment for metastatic NSCLC, as compared to platinum based chemotherapeutic compounds, among patient groups with varying levels of PD-L1 expression.

Key methods and patient characteristics

  • Randomised, open label, phase 3 trial involving patients with metastatic squamous or non-squamous NSCLC, conducted between July 21, 2015, and February 20, 2018.
  • Study restricted to patients that had not received prior treatment with any chemotherapeutic agents.
  • Positive PD-L1 expression on at least 1% of malignant cells or infiltrating immune cells, as assessed by SP142 immunohistochemical assay.
  • Patient randomised in 1:1 ratio to receive either Atezolizumab or platinum-based chemotherapy, with a total study sample size = 572 patients. Informed consent was received from all the patients.
  • Primary endpoint: overall survival evaluated according to PD-L1 expression levels.
  • Safety was assessed in all the patients regardless of PD-L1 expression.

Results

No of Pts

Pts with High PDL-1 Expression

Atezolizumab

285

107 (38.6%)

Chemotherapy

287

98 (35.4%)

Adverse Events

Overall

Grade 3 or 4

Atezolizumab

90.2%

30.1%

Chemotherapy

94.7%

30.1%

Conclusion

Treatment with atezolizumab monotherapy resulted in longer overall survival than platinum- based chemotherapy among patients with NSCLC with high PDL1 expression

References

The published manuscript can be accessed at – https://www.nejm.org/doi/full/10.1056/NEJMoa1917346
 

Information Source: Herbst et al. Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC. New England Journal of Medicine, 2020 Oct 1;383(14):1328-1339. PMID: 32997907 DOI: 10.1056/NEJMoa1917346

Disclaimer

The information presented in this article is for informational and educational purposesonly and does not substitute professional medical advice and consultation with healthcare professionals.

Copyright Reserved @2021

independent Publication from Biourbexer Solutions. Please contact us at Contact@biourbexer.com for any queries.
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Capsule Summary

Evaluation of Low-dose Pembrolizumab therapy in NSCLC patients

Advent of immune checkpoint inhibitors has created a paradigm shift for the treatment of numerous malignancies. Inhibitors targeting Programmed Cell Death-1 (PD1) receptor and its ligand PD-L1, alone or in combination with chemotherapy drugs represent the new standard of treatment for difficult to treat malignancies such as non-small cell lung carcinoma (NSCLC).
Although the pharmacokinetics studies using Pembrolizumab demonstrated PD-1 receptor saturation at 1 mg/kg, the clinical efficacy of Pembrolizumab in Phase III studies was evaluated at 2 mg/kg, and it is currently recommended at a dose of 200 mg every 3 weeks [1, 2]. However, biologics such as Pembrolizumab are very expensive therapeutics, and a dose reduction to achieve equivalent efficacy could be cost-effective for the patients and also reduce the overall healthcare burden.

Objective

Study objective: A study by Low et al. aimed to perform a retrospective analysis of the therapeutic benefit of low dose Pembrolizumab (100 mg) in Asian patients with advanced NSCLC [3].

Key methods and patient characteristics

  • Retrospective observational study among advanced stage NSCLC patients, receiving Pembrolizumab therapy between January 2016, and March 2020 at National University Hospital, Singapore.
  • 100 mg dose was routinely administered in patents lacking adequate financial resources or based on physician’s treatment preference.
  • Retrospective observational study among advanced stage NSCLC patients, receiving Pembrolizumab therapy between January 2016, and March 2020 at National University Hospital, Singapore.
  • Response classified as – progressive disease (PD), stable disease (SD), partial response (PR) or complete response.
  • Retrospective observational study among advanced stage NSCLC patients, receiving Pembrolizumab therapy between January 2016, and March 2020 at National University Hospital, Singapore.

Key study characteristics:

Chemotherapy

94.7%

30.1%

Outcomes

Interpretation: PFS and OS were not significantly different between the low dose 100 mg groups versus the 200 mg groups, in patients with pembrolizumab as a single agent therapyInterpretation: PFS and OS were not significantly different between the low dose 100mg groups versus the 200 mg groups, in patients with pembrolizumab as a single agent therapy

Other key study findings & Conclusion

PFS and OS were also not significantly different between the low dose versus high dose Pembrolizumab groups in patients receiving additional chemotherapy. No difference in response rates or >G3 immune-related toxicities observed. Cost analysis revealed a cost saving of astounding SGD 39,942 per patient in the Pembrolizumab 100 mg group.
A lower dose of Pembrolizumab (100 mg) appears to be effective in an Asian patient cohort, without any significant difference observed with respect of PFS, OS and adverse events as compared to the standard higher dose of 200 mg. Further studies employing randomised clinical trials are warranted, which if prove the equal efficacy of 100 mg Pembrolizumab, could save enormous expenditure on this expensive biologic treatment.

References

1. Gadgeel, S., et al., Updated Analysis From EYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexedand Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol, 2020. 38(14): p. 1505-1517.
2. Gandhi, L. and M.C. Garassino, Pembrolizumab plus Chemotherapy in Lung Cancer. N Engl J Med, 2018. 379(11): p. e18.
3. Low, J.L., et al., Low-dose pembrolizumab in the treatment of advanced non-small cell lung cancer. Int J Cancer, 2021. 149(1): p. 169-176.
4. Schwartz, L.H., et al., RECIST 1.1-Update and clarification: From the RECIST committee. Eur J Cancer, 2016. 62: p. 132-7.

Information Source:

 Low et al. Low-dose pembrolizumab in the treatment of advanced non-small cell lung cancer International journal of Cancer, 2021 Jul 1;149(1):169-176. PMID: 33634869 DOI: 10.1002/ijc.33534. Article access : https://onlinelibrary.wiley.com/doi/10.1002/ijc.33534.
https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html Accessed on 16th December 2021.

Disclaimer

The information presented in this article is for informational and educational purposesonly and does not substitute professional medical advice and consultation with healthcare professionals.

Copyright Reserved @2021

independent Publication from Biourbexer Solutions. Please contact us at Contact@biourbexer.com for any queries.
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Capsule Summary

Real World Evidence with First Line Pembrolizumab Monotherapy for Advanced NSCLC with PD-L1 Expression ≥ 50%

• Lung Cancer is the third most common cancer in the United States. It remains the leading cause of death in men and women.
• Immune checkpoint inhibitors have revolutionized cancer management. These drugs are a part of immunotherapy which ensures the destruction of the cancer cells by the immune system of our body.
• Pembrolizumab, Nivolumab, Atezolizumab, Durvalumab, Cemiplimab, and Avelumab are the drugs from this class that has been approved by the US FDA for the treatment of different cancers. These drugs target a pathway called the PD-1(Programmed cell death protein 1)/PD-L1 (Programmed death-ligand 1).
• The PD-1 inhibitor pembrolizumab (Brand name- Keytruda) especially received wide media coverage as it helped cure former US president Jimmy Carter who was suffering from metastatic melanoma (skin cancer) which had spread to his liver and brain.
• In 2019, the PD-1 inhibitor Pembrolizumab was approved by the US FDA as a first-line monotherapy for the treatment of Non-Small Cell Lung Cancer (NSCLC. The PD-1/PD-L1 inhibitors class of drugs has revolutionized cancer management and has emerged as a major class of drugs for the treatment of different cancers.
• A study was recently published that evaluated the real-world time on treatment (rwToT), overall and by KRAS mutation status, with first-line pembrolizumab monotherapy for advanced non-small cell lung cancer (NSCLC) in real-world oncology practice in the US.

The summary of the study is as follows:

Methodology: Using de-identified electronic medical record data, the researchers studied patients with ECOG performance status (PS) of 0–2 who initiated pembrolizumab (1 November 2016 to 31 March 2020) for advanced NSCLC with programmed death-ligand 1 (PD-L1) expression ≥ 50% and without EGFR/ALK/ROS1 genomic alterations. The data cutoff was 31 March 2021, and the median study follow-up was 34 months.

Results:

• The Kaplan–Meier median rwToT with first-line pembrolizumab monotherapy was 7.4 months (95% CI, 6.3–8.1) for 807 patients with PS 0–1.
• The above results were consistent with the Key Note trial where the median treatment duration was 7.9 months.
• The median rwToT for 237 patients with PS 2 was 2.1 months (95% CI, 1.4–2.8).
• Median rwToT in patients with KRAS-mutated and KRAS wild-type nonsquamous NSCLC and PS 0–1 was 7.6 months and 7.0 months, respectively.
 

Conclusion:

Study findings suggested that there was the long-term benefit of first-line pembrolizumab monotherapy for advanced NSCLC with PD-L1 expression ≥ 50% in real-world settings in the US, particularly for patients with good performance status at the start of therapy, irrespective of KRAS status.

Information Source:

 You can access the full article at https://www.mdpi.com/2072-6694/14/4/1041/htm

Disclaimer

The information presented in this article is for informational and educational purposesonly and does not substitute professional medical advice and consultation with healthcare professionals.

Copyright Reserved @2021

independent Publication from Biourbexer Solutions. Please contact us at Contact@biourbexer.com for any queries.
Download PDF

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