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WCLC 2023 Expert Perspectives

CE / CME

2023 World Conference on Lung Cancer: Expert Perspectives on Key Studies

Physician Assistants/Physician Associates: 1.50 AAPA Category 1 CME credits

Nurses: 1.50 Nursing contact hours

Physicians: maximum of 1.50 AMA PRA Category 1 Credits™

Pharmacists: 1.50 contact hours (0.15 CEUs)

Released: November 17, 2023

Expiration: November 16, 2024

Matthew Gubens
Matthew Gubens, MD, MS, FASCO
Helena Yu
Helena Yu, MD
CME/CE Information

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LUNAR Subgroup Analysis: TTFields + Immune Checkpoint Inhibition in Metastatic NSCLC After Platinum Failure by PD-L1 Expression

Matthew Gubens, MD, MS:
Now we will move on to something completely different, the use of tumor-treating fields (TTFields) in the management of advanced NSCLC.

TTFields work by applying alternating current electrical fields with low intensity (1-3 V/cm) and intermediate frequency (100-300 kHz) to electrically charged components in dividing cancer cells, resulting in antimitotic effects, as well stress-induced immunogenic cell death.57,58 TTFields are delivered via a wearable medical device—a chest vest that has 2 pairs of arrays—and they are worn for at least 18 hours per day. TTFields devices have FDA approval for glioblastoma and advanced pleural mesothelioma.59,60

In the phase III LUNAR trial, 276 adult patients with metastatic NSCLC who had progressed on prior platinum-based CT were randomized 1:1 to receive TTFields in combination with investigator's choice of ICI (pembrolizumab, nivolumab, or atezolizumab) or docetaxel or either systemic therapy alone.61 The primary endpoint was OS, with secondary endpoints including OS by treatment subgroup (ICI vs CT), PFS, ORR, QoL, safety, and PFS/OS by histology.

Of note, this trial was mostly conducted before chemoimmunotherapy became a preferred standard first-line treatment strategy for advanced NSCLC vs CT alone, so the patient population in LUNAR is one that, for the most part, is not seen anymore.

In results presented at the 2023 American Society of Clinical Oncology Annual Meeting, the phase III LUNAR trial met its primary endpoint, with TTFields plus investigator’s choice of systemic therapy significantly improving median OS (18.5 months vs 10.8 months; HR: 0.74; 95% CI: 0.56-0.98; P = .035) compared with systemic therapy alone in patients with metastatic NSCLC and progression on/after platinum-based therapy. However, there was no significant difference in PFS between the 2 arms.

A post hoc exploratory analysis focused on OS by PD-L1 status in the ICI-treated subgroup was presented at WCLC 2023.62

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LUNAR Subgroup Analysis: Baseline Characteristics of ICI-Treated Subgroup

Matthew Gubens, MD, MS:
For this subgroup analysis of TTFields plus ICI vs ICI alone, baseline characteristics were well balanced for median age (64 years vs 65 years), smoking status (85% vs 82% current or former smokers), and tumor histology (56% vs 54% nonsquamous), and nearly all patients had received 1 prior line of systemic therapy. There were a large number of patients with unknown PD-L1 TPS score (49% of TTFields plus ICI group; 38% of ICI group), resulting in a lower number of patients with PD-L1 ≥50% than would be expected (8% and 12%, respectively)—we typically expect one third each for PD-L1 <1%, 1% to 49%, and ≥50%.

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LUNAR Subgroup Analysis: OS in ICI-Treated Subgroup by PD-L1 Status

Matthew Gubens, MD, MS:
The presentation at WCLC 2023 evaluated OS by PD-L1 status only in patients who received ICI treatment, which resulted in relatively small patient populations in each subgroup: n = 12 with PD-L1 <1%, n = 22 with PD-L1 1% to 49%, and n = 5 with PD-L1 ≥50%. In the group of patients with PD-L1 <1%, median OS was similar for TTFields plus ICI vs ICI alone (9.6 months vs 9.1 months; HR: 0.98; 95% CI: 0.42-2.24; P = .95). However, in the PD-L1 ≥1% subgroup, the median OS was considerably different between the 2 groups: 23.6 months with TTFields plus ICI vs 10.5 months with ICI alone (HR: 0.49; 95% CI: 0.24-1.00; P = .045). Finally, the difference in median OS between TTFields plus ICI vs ICI alone appeared more pronounced for patients with PD-L1 ≥50% (HR: 017; P =.07) vs PD-L1 1% to 49% (HR: 0.55; P =.14), although, again, these are very small patient populations.

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LUNAR Subgroup Analysis: Safety in ICI-Treated Subgroup

Matthew Gubens, MD, MS:
TTFields is thought to be a relatively safe therapy, and findings in this subgroup analysis were consistent with the overall study results. Device-related toxicity was seen in 73% of patients treated with TTFields plus ICI, mostly grade 1/2 dermatitis, and there were no deaths or grade 4 AEs due to TTFields therapy.

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LUNAR Subgroup Analysis: Clinical Implications

Matthew Gubens, MD, MS:
TTFields technology was approved for malignant pleural mesothelioma several years ago, but I have yet to use it in that setting. This is primarily because the phase II STELLAR trial upon which its approval is based was a single-arm trial without a control arm.

Here, in advanced NSCLC, the phase III LUNAR trial was randomized and controlled, but as mentioned above, the entry criterion for patients to have progressive disease on or after platinum-based CT is out of date, with the new first-line SoC being chemoimmunotherapy for advanced NSCLC without an actionable genomic aberration. This makes it challenging to apply these data to patients in the current treatment landscape.

Helena Yu, MD:
Like you, I have not used TTFields in clinical practice but applaud the fact that this is a randomized, controlled study. However, anytime a study shows a clear OS benefit without a PFS benefit, it raises questions. For example, was the observed OS benefit influenced by the fact that one arm required a lot more nursing care and closer follow-up than the other arm? I do think that it is very intriguing technology, and I am sure we will hear more about it.

Phase III EMPOWER-Lung 1 and 3: Updated
Long-term Subgroup Analysis of Cemiplimab in Newly Diagnosed Advanced NSCLC With Liver Metastases

Matthew Gubens, MD, MS:
The PD-1 inhibitor cemiplimab is approved by the FDA as monotherapy and in combination with platinum-based CT for first-line treatment of adult patients with locally advanced (not candidates for resection or definitive chemoradiation) or metastatic (without EGFR, ALK, or ROS1 aberrations) NSCLC and high PD-L1 expression (TPS ≥50%) or regardless of PD-L1 expression, respectively.63 These approvals are based on the phase III EMPOWER-Lung 1 and EMPOWER-Lung 3 part 2 trials, which showed significantly improved survival for first-line cemiplimab monotherapy and combination therapy with CT, respectively, compared with CT alone.64-66

At WCLC 2023, an exploratory subgroup analysis from the EMPOWER-Lung 1 and 3 studies looked at efficacy and safety of cemiplimab with or without CT in patients with advanced NSCLC and baseline liver metastases.67

EMPOWER-Lung 1 and 3 Updated Analysis of Patients With Liver Metastases: Efficacy With Cemiplimab-Based Regimens

Matthew Gubens, MD, MS:
Outcomes for patients with liver metastases at baseline generally were worse compared with those without, but a clear benefit was still seen with cemiplimab-based therapy compared with CT alone.67

In EMPOWER-Lung 1 (patients with PD-L1 ≥50%), cemiplimab monotherapy prolonged median OS (20.4 months vs 7.6 months; HR: 0.53; 95% CI: 0.31-0.89) and median PFS (6.3 months vs 4.2 months; HR: 0.43; 95% CI: 0.26-0.71) compared with CT alone. In EMPOWER-Lung 3 part 2 (patients with any PD-L1 expression), cemiplimab plus CT prolonged median OS (15.5 months vs 8.9 months; HR: 0.65; 95% CI: 0.35-1.20) and median PFS (5.4 months vs 4.2 months; HR: 0.66; 95% CI: 0.37-1.16) compared with placebo plus CT.

There were no new safety signals compared with the analysis of the full study populations.

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EMPOWER-Lung 1 and 3 Updated Analysis of Patients With Liver Metastases: Clinical Implications

Matthew Gubens, MD, MS:
The subgroup analysis presented here is further evidence that first-line cemiplimab-based regimens, whether alone or in combination with CT, are very effective in patients with liver metastases compared with CT alone. I always appreciate seeing data from our higher-risk patient populations—liver metastases being one.

In an exploratory subgroup analysis from the EMPOWER-Lung 1 and 3 studies, a survival benefit was reported for patients with newly diagnosed advanced NSCLC and baseline liver metastases with which of the following cemiplimab-based regimens compared with CT?

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