International Hybrid Lung Cancer Congress Focuses on Multimodal Treatment

Elucidating clinical trial results so that they can be incorporated into the daily workflow of lung cancer care delivery remains a common theme of the 22nd Annual International Lung Cancer Congress® hosted by Physicians’ Education. Resource®, LLC (PER®), a goal that continues from the early days of the meeting, said Roy S. Herbst, MD, PhD, conference co-chair.1 In an interview with Targeted therapies in oncology, Herbst discussed the upcoming conference on July 29 and 31, which will follow a hybrid format with some faculty and participants attending online and others attending in person.

Like many meetings last year, this conference was held virtually. But because of this year’s hybrid format, “I’m going to get to the conference by hook or by crook,” Herbst said. “I look forward to the meeting every year and enjoy the in-person interaction.” In addition to the cochair lecture, Herbst is the Ensign Professor of Medicine (Medical Oncology), Professor of Pharmacology, Chief of Medical Oncology and Associate Director of the Cancer Center for Translational Science at Yale Cancer Center and Smilow Cancer Hospital in New Haven, Connecticut. . During the 3-day conference, general topics including early stage chest malignancies, oncogenic fusions, targeting the HER family, novel therapeutic strategies, combined modalities in non-small cell lung cancer (NSCLC) stage III immunotherapy and molecule tests will serve as benchmarks for participants.

Specific presentations will address the ongoing issues of the ADAURA trial (NCT02511106), the multiple treatment options available for ROS1-positive NSCLC, enhancement of first-line osimertinib (Tagrisso) activity, use of immunotherapy in early NSCLC, numerous Medical Crossfire® discussions, and appropriate use of liquid biopsies to provide participants with advice on these difficult clinical issues (BOX).

“This year’s conference will focus a lot of attention on unique and interesting cases, [and] this will foster and encourage many discussions between faculty and participants, ”Herbst said, noting that other conference co-chairs, David R. Gandara, MD, and Heather A. Wakelee, MD, were instrumental in the development of cases and round tables. , ensuring that each discussion leaves enough time for questions and answers and a multimodal focus.

Recent tests

Although not officially included on the agenda, Herbst anticipates extensive discussion at the interim outcome conference of the IMpower010 study (NCT02486718), which evaluated the safety and efficacy of aitzolizumab (Tecentriq ) and Best Supportive Care (BSC) in adjuvant adjustment of NSCLC.

Researchers have reported an improvement in disease-free survival (DFS) compared to CSB when given as an adjuvant treatment after surgery and chemotherapy in patients with stage II-IIIA NSCLC.1

In the study, 1005 patients were randomized to receive 16 cycles of intravenous (IV) aezolizumab 1200 mg every 2 weeks for up to 21 days. Patients received either IV cisplatin 75 mg / m2 on day 1 of up to four 21-day cycles, vinorelbine IV 30 mg / m2 given on days 1 and 8, docetaxel IV 75 mg / m2 given on day 1, IV gemcitabine 1250 mg / m2 given on days 1 and 8, or pemetrexed IV 500 mg / m2 given on day 1. The same chemotherapy agents, strengths and dosing schedules were used in the BSC group.

Going forward, planned analyzes of DFS and overall survival in the overall intention-to-treat population of IMpower010 will continue with patient follow-up to recover immature data at the time of interim analysis, according to Genentech, the manufacturer of atezolizumab. Safety analysis of the trial has been completed and has shown consistency with the previously known safety profile of aezolizumab.

Herbst said the results of the CheckMate 816 trial (NCT02998528) will likely also be discussed. The randomized, open-label phase 3 study evaluated nivolumab (Opdivo) plus chemotherapy versus chemotherapy alone as a neoadjuvant treatment for resectable NSCLC. Patients were randomized to receive either nivolumab plus platinum doublet chemotherapy (n = 179) or chemotherapy alone (n = 179), followed by surgery. Pathologic complete response (pCR) was the primary endpoint.

The results demonstrated a statistically significant improvement in pCR (odds ratio, 13.94; 99% CI, 3.49-55.75; P<.0001 and the benefit was consistent across disease stages histologies tumor mutation burden pd-l1 expression levels. investigators reported that adding nivolumab to chemotherapy maintained a tolerable safety profile.>2

Exploratory subset analysis showed that clearance of circulating tumor DNA was more frequent with the combination than with monotherapy and appeared to be associated with pCR.2

EGFR inhibitors

Herbst, who has worked for decades as a pioneer in personalized medicine and immunotherapy to identify biomarkers and provide new targeted therapies and immunotherapies to patients, said he considers his work on the use of inhibitors EGFR as the most impactful.

“Improving our understanding of personalized immunotherapy by identifying the right biomarkers continues to be of great importance,” said Herbst. He was a co-author of the general phase 2 BATTLE trial (NCT00409968, NCT00411671, NCT00411632, NCT00410059, NCT00410189), which randomized a total of 255 patients with chemo-refractory erlotinib NSCLC (Tarceva; n = 59) ), vandetanib (Caprelsa; 54), erlotinib plus bexarotene (n = 37) or sorafenib (Nexavar; n = 105) based on molecular biomarkers of the pathogenesis of NSCLC.

Of these, 244 were eligible for disease control rate (DCR) analysis. Overall, the researchers reported an 8-week DCR of 46%, a median progression-free survival of 1.9 months, a median overall survival of 9 months, and a 35% survival at 1 year.3

Individual markers predicting significantly higher DCR for included treatment EGFR mutation (P = 0.04) for erlotinib; cyclin D1 positivity (P = .01) or EGFR amplification (P = 0.006) for erlotinib plus bexarotene; vascular endothelial growth factor receptor 2 positivity (P = 0.05) for vandetanib; and the absence of EGFR mutation (P = .01) or EGFR high polysomy (P = 0.05) for sorafenib.3

Comparing DCRs among treatment arms, researchers noted a better DCR at 8 weeks for sorafenib compared to all other regimens (64% vs. 33%; P <.001 in patients with>EGFR wild type and compared to all other regimens (61% vs 32%; P = .11) in patients with KRAS mutations.

Returning to the meeting, Herbst said a number of other topics will likely be covered, including: How is immune resistance defined and what combination of therapies can be used to combat immune resistance? How do you use pCR-based neoadjuvant therapies?

“I think these topics are all important,” Herbst said. “In general, PER® meetings tend to focus on providing usable information that physicians can take home and apply immediately to the clinic.”

The references:

1. The pivotal phase III study shows that Tecentriq from Genentech has helped people with early-stage lung cancer live longer without their disease coming back. Press release. Genentech. March 22, 2021. Accessed April 23, 2021. https: //

2. Forde PM, Spicer J, Lu S et al. Nivolumab + platinum doublet chemotherapy vs chemotherapy as a neoadjuvant treatment for resectable non-small cell lung cancer (IB-IIIA) in the phase 3 study CheckMate 816. Presented at: American Association for Cancer Research Annual Meeting 2021; April 10 to 15, 2021; virtual.

3. Kim ES, Herbst RS, Wistuba II et al. The BATTLE Trial: Personalizing Lung Cancer Therapy. Cancer Discov. 2011; 1 (1): 44-53. doi: 10.1158 / 2159- 8274.CD-10-0010

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