Dr Garon on Considerations for Perioperative Immunotherapy Use in Lung Cancer

Edward B. Garon, MD, MS, professor of medicine, Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, the University of California, Los Angeles (UCLA), UCLA Health, discusses key considerations when selecting an optimal perioperative treatment approach for patients with lung cancer.

As the field of lung cancer continues to rapidly develop, data from numerous studies tend to be concurrently read out and compared with the same standard of care, Garon begins. This deluge of information can complicate data interpretation. However, the current body of evidence is increasingly supporting the integration of immunotherapy into the perioperative space, he says. The primary challenge now is determining the optimal amount of chemoimmunotherapy to administer to patients, and whether adjuvant immunotherapy is necessary for those who have already received chemoimmunotherapy before surgery, Garon explains.

Cross-trial comparisons suggest that continuing treatment with adjuvant therapy might be advantageous even for patients who received neoadjuvant therapy, Garon continues. However, this hypothesis needs validation through randomized trials, which are currently lacking, he notes, adding that this gap in data creates uncertainty about the best course of action in these treatment sequences.

Moreover, there is a noticeable disparity in the adoption of neoadjuvant chemoimmunotherapy between academic centers and community practice settings, Garon says. Academic centers are more inclined to incorporate chemoimmunotherapy before surgery, specifically for patients with lymph node–positive disease who will likely require adjuvant therapy, he explains. This approach is based on strong data and theoretical benefits, suggesting that neoadjuvant therapy might be more effective than adjuvant therapy alone, Garon states.

The enthusiasm for neoadjuvant chemoimmunotherapy in academic settings is driven by the belief that it can provide better outcomes for patients needing systemic therapy, Garon details. However, it is necessary to assess whether this enthusiasm for neoadjuvant chemoimmunotherapy is resonating with broader clinical practice, he notes. Understanding if healthcare providers outside of academic centers are recognizing and adopting these strategies is crucial, Garon emphasizes. This insight could help bridge the gap between research findings and real-world application, ensuring that patients across different treatment settings receive the most effective care, he concludes.

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Edward B. Garon, MD, MS, discusses key considerations when selecting an optimal perioperative treatment approach for patients with lung cancer.

Edward B. Garon, MD, MS, professor of medicine, Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, the University of California, Los Angeles (UCLA), UCLA Health, discusses challenges associated with the incorporation of immunotherapy into the treatment paradigm for 

-mutant non–small cell lung cancer (NSCLC).

Attempts to incorporate immunotherapy approaches into the treatment landscape for patients with 

-mutant NSCLC have been met with several challenges, Garon begins. Historically, response rates with single-agent PD-1/PD-L1 inhibitors in this population have been low, he says. Despite some encouraging early data, efforts to improve sensitivity to such approaches using CTLA-4 inhibition have not shown conclusive success, Garon states.

In a study of frontline immunotherapy approaches conducted by Aaron Lisberg, MD, of UCLA, patients who received an EGFR inhibitor following treatment with a PD-1 inhibitor did not experience sufficient benefit, Garon continues. Moreover, these patients also experienced high toxicities.

Conversely, the efficacy of angiogenesis inhibition plus PD-1 or PD-L1 inhibition and chemotherapy in this population has been demonstrated by 2 key trials, Garon reports. The phase 3 IMpower150 trial (NCT02366143) of atezolizumab (Tecentriq) plus bevacizumab (Avastin), carboplatin, and paclitaxel demonstrated improved overall survival with the experimental combination vs bevacizumab and chemotherapy in patients with metastatic nonsquamous NSCLC. Based on these results, a replication study was conducted by a group in China to evaluate a PD-1 inhibitor plus a biosimilar of the antiangiogenic agent.

As data from these trials continue to mature, researchers may identify biomarkers that are predictive of patient benefit, Garon says. This would allow for improved selection of patients with 

 mutations for immunotherapy regimens, he concludes.

Dr Garon has reported consulting or advisory roles with AbbVie, ABL-Bio, AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Dracen Pharmaceuticals, EMD Serono, Eisai, Eli Lilly, Gilead, GlaxoSmithKline, Ipsen, Merck, Natera, Novartis, Personalis, Regeneron, Sanofi, Shionogi, and Xilio; and has received grant/research support from ABL-Bio, AstraZeneca, Bristol Myers Squibb, Dynavax Technologies, Eli Lilly, EMD Serono, Genentech, Iovance Biotherapeutics, Merck, Mirati Therapeutics, Neon Therapeutics, and Novartis.

Edward B. Garon, MD, MS, discusses challenges associated with the incorporation of immunotherapy into the treatment paradigm for EGFR-mutant non–small cell lung cancer. 

Dr Garon on Challenges Associated With Immunotherapy Use in EGFR-mutated NSCLC

Edward B. Garon, MD, MS, professor of medicine, Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, the University of California, Los Angeles (UCLA), UCLA Health, discusses the use of PD-L1 inhibitor and CTLA-4 inhibitor combinations in non–small cell lung cancer (NSCLC).

There are currently 2 first-line PD-L1 and CTLA-4 inhibitor combinations approved by the FDA for use in NSCLC, Garon begins.

The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) plus 2 cycles of platinum-based chemotherapy gained approval in May 2020 for patients with metastatic and recurrent NSCLC without 

 alterations, Garon says. The combination of nivolumab and ipilimumab was first approved for patients with PD-L1 positivity based on findings from the phase 3 CheckMate-227 trial (NCT02477826). Shortly after, the triplet was approved for use in patients regardless of PD-L1 expression based on findings from the phase 3 CheckMate-9LA trial (NCT03215706).

Data from the phase 3 POSEIDON study (NCT03164616) led to the FDA approval of durvalumab (Imfinzi) and tremelimumab (Imjudo) plus chemotherapy in this same population on November 10, 2022, Garon continues. Patients in this trial were randomized to either 4 cycles of tremelimumab, durvalumab, and platinum-based chemotherapy followed by durvalumab and maintenance chemotherapy every 4 weeks and a fifth tremelimumab dose at week 16; 4 cycles of durvalumab plus chemotherapy followed by durvalumab and maintenance chemotherapy; or 6 cycles of chemotherapy followed by maintenance chemotherapy.

Patients in the POSEIDON trial received a greater number of chemotherapy cycles than patients in CheckMate-9LA, who received only 2 cycles in the experimental arm, Garon notes. However, patients in the CheckMate-227 and CheckMate-9LA trials continued ipilimumab treatment compared with patients in POSIDEON who received only 1 cycle of post-chemotherapy tremelimumab, Garon qualifies.

These variations in the treatment schedule for these regimens produce different toxicity profiles, Garon continues. For example, the CheckMate-9LA approach allows for earlier chemotherapy cessation, reducing chemotherapy-related toxicities, he explains. Conversely, the POSEIDON regimen incorporates an earlier cessation of tremelimumab, Garon says. As CTLA-4 inhibitors are known to produce significant immune-related toxicities, this approach could also reduce adverse effects, Garon concludes.

Editor’s Note: Dr. Garon has reported consulting or advisory roles with Abbvie, ABL-Bio, AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Dracen Pharmaceuticals, EMD Serono, Eisai, Eli Lilly, Gilead, GlaxoSmithKline, Ipsen, Merck, Natera, Novartis, Personalis, Regeneron, Sanofi, Shionogi, and Xilio; and has received grant/research support from ABL-Bio, AstraZeneca, Bristol Myers Squibb, Dynavax Technologies, Eli Lilly, EMD Serono, Genentech, Iovance Biotherapeutics, Merck, Mirati Therapeutics, Neon Therapeutics, and Novartis.

Edward B. Garon, MD, MS,  discusses the use of PD-L1 inhibitor and CTLA-4 inhibitor combinations in non–small cell lung cancer.

Dr. Garon on the Current Landscape of PD-L1 and CTLA-4 Inhibitor Regimens in NSCLC

Edward B. Garon, MD, professor of medicine, Division of Hematology/Oncology, Department of Medicine, Geffen School of Medicine at UCLA, discusses the efficacy of datopotamab deruxtecan (DS-1062a) in patients with non–small cell lung cancer (NSCLC), as reported in the phase 1 TROPION-PanTumor01 trial (NCT03401385).

TROPION-PanTumor01, data of which were presented during the 

International Association for the Study of Lung Cancer 2021 World Conference on Lung Cancer

, is a large study examining the agent in patients with other solid tumor cohorts in addition to NSCLC, according to Garon.

The study includes dose-expansion cohorts in which the agent is being administered at the following doses: 4 mg/kg (n = 50), 6 mg/kg (n = 50), and 8 mg/kg (n = 80). Notably, efficacy was observed at all dose levels in this heavily pretreated patient population, and was not limited to the highest dose of 8 mg/kg, Garon says.

Ultimately, the 8-mg/kg dose was associated with more toxicity, and the 6-mg/kg dose was chosen to be examined in further studies, Garon notes. Moreover, response rates experienced at the 6-mg/kg dose and 4-mg/kg doses were similar, at 28% and 24%, respectively, Garon concludes.

Edward B. Garon, MD, discusses the efficacy of datopotamab deruxtecan in patients with non–small cell lung cancer, as reported in the phase 1 TROPION-PanTumor01 trial. 


Dr. Garon on the Efficacy of Datopotamab Deruxtecan in NSCLC

Edward Garon, MD, assistant professor of Medicine, Department of Medicine, Division of Hematology/Oncology, Geffen School of Medicine at University of California, Los Angeles, discusses incorporating immunotherapies into the treatment of patients with lung cancer.

The PD-1 inhibitors pembrolizumab (Keytruda) and nivolumab (Opdivo) are both approved for the treatment of previously treated patients with metastatic non—small cell lung cancer (NSCLC), Garon explains. The main difference between the agents, he adds, is the requirement of a biomarker: Pembrolizumab is indicated for the treatment of patients with NSCLC whose tumors express PD-L1, while this is not the case for nivolumab.

The safety profiles between the two agents are fairly similar, though the drugs have not been compared in a head-to-head trial.

dward Garon, MD, assistant professor of Medicine, Department of Medicine, Division of Hematology/Oncology, Geffen School of Medicine at University of California, Los Angeles, discusses incorporating immunotherapies into the treatment of patients with lung cancer.

Edward Garon, MD

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Dr Garon on Considerations for Perioperative Immunotherapy Use in Lung Cancer

Dr Garon on Challenges Associated With Immunotherapy Use in EGFR-mutated NSCLC

Dr. Garon on the Current Landscape of PD-L1 and CTLA-4 Inhibitor Regimens in NSCLC

Dr. Garon on the Efficacy of Datopotamab Deruxtecan in NSCLC

Dr. Garon on Incorporating Immunotherapies Into Lung Cancer Treatment