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What is the new treatment for non-small cell lung cancer? Changes in the Perioperative Setting [54 Slides] Karen Reckamp, MD

What is the new treatment for non-small cell lung cancer? Changes in the Perioperative Setting [54 Slides] Karen Reckamp, MD

What is the new treatment for non-small cell lung cancer? Changes in the Perioperative Setting [54 Slides] Karen Reckamp, MD

At the MOASC Annual Oncology Summit & Research Symposium, Dr. Karen Reckamp, MD, MS, a leading figure in medical oncology at Cedars-Sinai, Los Angeles, CA, provided a comprehensive update on the transformative approaches in the perioperative management of non-small cell lung cancer (NSCLC). With a distinguished career marked by contributions to advancing treatment modalities, Dr. Reckamp’s insights into the integration of immunotherapy and targeted therapy in NSCLC offer valuable perspectives for oncologists navigating this evolving landscape.

Oncogenic Drivers and Treatment Evolution in NSCLC

The journey of NSCLC treatment has been significantly influenced by the understanding of oncogenic drivers and the tumor microenvironment. This section delves into how these insights have paved the way for targeted and immune-based therapies, transforming patient care.

The Rise of Checkpoint Inhibitors

Checkpoint inhibitors, particularly pembrolizumab, have become cornerstone treatments across various stages of lung cancer. The PEARLS and KN-671 studies underscore pembrolizumab’s efficacy, highlighting its role in mesothelioma treatment and setting a precedent for its inclusion in standard care protocols.

Immunotherapy’s Early Integration

The landmark approval of peri-operative pembrolizumab (KN-671) marks a significant shift towards incorporating immunotherapy early in the treatment continuum. This strategic move aims to improve outcomes by targeting micrometastatic disease more effectively, a concept supported by emerging evidence and regulatory endorsements.

Treatment Timing in Early-Stage NSCLC: A Closer Look

Choosing between neoadjuvant and adjuvant therapy involves a careful consideration of benefits and challenges. This section expands on the unique advantages of each approach, supported by recent studies and clinical insights.

Neoadjuvant Therapy: A Proactive Approach

Neoadjuvant therapy offers several benefits, including the potential to eradicate micrometastatic disease before surgery and providing an early indicator of therapy response. The increased treatment initiation rate and compliance, alongside the ability to guide future treatment decisions based on pathologic response, underscore its value.

Adjuvant Therapy: Post-Surgical Advantages

Conversely, adjuvant therapy allows for immediate surgical intervention, minimizing the risk of systemic therapy-related complications before surgery. This approach also accommodates more extended treatment durations for systemic control and offers flexible timing for patient recovery post-surgery.

Adjuvant Therapy’s Role in Early-Stage NSCLC

This section explores the nuanced impact of adjuvant therapy across different stages of NSCLC, drawing from retrospective analyses and pivotal trials like CALGB, JBR.10, ALPI, IALT, ANITA, and LACE.

Phase III Trials: IMpower010 and Keynote-091

The IMpower010 trial comparing adjuvant atezolizumab with best supportive care and the Keynote-091 trial evaluating pembrolizumab have both reinforced the value of immunotherapy in the adjuvant setting for resected stage IB-IIIA NSCLC patients, especially those with PD-L1 TC ≥1%.

Neoadjuvant Immunotherapy: Rationale and Evidence

Focusing on stage IIIA NSCLC, this section highlights the rationale behind neoadjuvant immunotherapy. The CheckMate 816 trial is presented as a landmark study demonstrating significant pathologic response and survival benefits with neoadjuvant nivolumab and chemotherapy.

CheckMate 816 and IMpower010: Detailed Outcomes

A more detailed look into the CheckMate 816 trial reveals the efficacy of neoadjuvant nivolumab and chemotherapy in achieving pathologic complete response (pCR) rates and improving event-free survival (EFS). Similarly, the IMpower010 trial underscores the survival advantage of adjuvant atezolizumab following surgery and platinum-based chemotherapy in patients with PD-L1 TC ≥1%.

The Integration of Targeted Therapy in Early-Stage NSCLC

With targeted therapies showing promise in the adjuvant setting, particularly EGFR TKIs like osimertinib as evidenced by the ADAURA study, this section explores their potential to improve outcomes in early-stage NSCLC driven by various oncogenes, including the phase 3 ALINA study of adjuvant alectinib versus chemotherapy in resectable stage IB-IIIA ALK+ NSCLC.

Comprehensive Review of Phase III Trials

An exhaustive analysis of phase III trials, including the AEGEAN study of neoadjuvant durvalumab plus chemotherapy in patients with resectable stage IIA-IIIB NSCLC and the CheckMate 77T study of neoadjuvant nivolumab followed by surgery and adjuvant nivolumab for patients with resectable stage II-IIIB NSCLC, provides a thorough understanding of the evolving treatment paradigms

Reference Links:

Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial: https://pubmed.ncbi.nlm.nih.gov/34555333/

Pembrolizumab vs placebo for early-stage non‒small-cell lung cancer after resection and adjuvant therapy: Subgroup analysis of patients who received adjuvant chemotherapy in the phase 3 PEARLS/KEYNOTE-091 study.: https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.8520

OncologyTube Links:

IMpower010 Unveiled: A Fresh Look at Atezolizumab in Lung Cancer: https://oncologytube.com/impower010-unveiled-a-fresh-look-at-atezolizumab-in-lung-cancer/

Keynote-091: https://oncologytube.com/mary-o-brien-md-drmaryobr-royalmarsdennhs-asco22-oncotwitter-phase-iii-pearls-keynote-091-discussion/

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