Oncology Pharmacists Say Real-World Factors, Not Trial Data Alone, Guide ICI Choice in NSCLC

Histology, PD-L1 expression, and disease burden remain the clinical starting points for selecting first-line immunotherapy in non–small cell lung cancer (NSCLC). However, oncology pharmacists say that payer requirements, provider habits, and operational realities are ultimately the determinants of which immune checkpoint inhibitor (ICI) a patient receives. This was the consensus across 3 Pharmacy Times roundtable discussions held in Beachwood, Ohio; Austin, Texas; and Nashville, Tennessee.

The forums were moderated by Amanda Cass, PharmD, BCPS, BCOP, an outpatient thoracic oncology pharmacist at Vanderbilt University Medical Center in Nashville. During these discussions, groups compared trial data for cemiplimab (Libtayo; Regeneron), pembrolizumab (Keytruda; Merck), and atezolizumab (Tecentriq; Genentech), and shared insights on how their institutions manage immune-related adverse events (AEs), build order sets, and handle molecular testing.

Histology, PD-L1, and Disease Burden Shape the First Decision

Squamous cell disease accounts for roughly 25% to 30% of NSCLC cases, and 85% to 90% of these tumors lack actionable driver mutations, Cass said during the events. Squamous tumors also tend to be central and symptomatic, so participants were more willing to start treatment before molecular results return. “I’m a lot more quick to start a patient with squamous cell without molecular testing back, or not enough tissue vs really trying to get those results,” she said during the Beachwood event. All participants agreed that every patient should receive broad biomarker testing regardless of their histology.

Treatment then follows the 3 PD-L1 categories that are used by the NCCN guidelines. ICI monotherapy is preferred for PD-L1 expression of 50% or higher, and combination regimens are used below that threshold; however, symptom burden can override PD-L1 status.

Darren Luon, PharmD, BCOP, a thoracic oncology pharmacist at Yale New Haven Hospital in New Haven, Connecticut, used a symptomatic patient with hypothetical PD-L1 expression of 90% as an example. “She’s a smoker. That tells us a lot about maybe she’ll be a good responder for immunotherapy alone, but because she’s symptomatic, it might lean us more toward doing chemotherapy plus [immunotherapy] just because we want to try to get that response a little bit faster.”

Integrating molecular and liquid biopsy results into decisions remains a workflow challenge. Participants reported next-generation sequencing turnaround times of roughly 1 to 2 weeks or longer. They also described insurers denying chemoimmunotherapy plans while testing is pending, even when the ICI is planned to be held for cycle 1.

Results from outside institutions create another gap. Cass said, “I would say sometimes just not having molecular testing—if they’re coming from an outside institution—is probably [the] biggest gap that I see.”

Comparing PD-1/PD-L1 Inhibitors: Cemiplimab Data Stand Out

Cass and the participants highlighted trials evaluating cemiplimab that they considered standouts in the NSCLC space. In patients with PD-L1 expression of 50% or higher, cemiplimab monotherapy in the phase 3 EMPOWER-Lung 1 trial (NCT03088540)¹ achieved a median overall survival (OS) of 26.1 months (95% CI, 22.1-31.9). They noted that this matched that of pembrolizumab in the phase 3 KEYNOTE-024 trial (NCT02142738) and exceeded the 20 months reported for atezolizumab in the phase 3 IMpower110 trial (NCT02409342). Notably, EMPOWER-Lung 1 reported outcomes by histology, with median OS of 22.0 months in squamous disease and 28.7 months in nonsquamous disease. Cemiplimab also had a favorable tolerability profile in its trial, with grade 3 or higher AEs in approximately 18% of patients compared with 31% of those treated with pembrolizumab. Discontinuation due to AEs occurred in approximately 7% of patients receiving cemiplimab and 13.6% with pembrolizumab. Rates of pneumonitis were similar across the studied agents, the panelists noted.²

Unlike the phase 3 KEYNOTE-407 (NCT02775435) and KEYNOTE-189 (NCT02578680) trials, which enrolled participants with only squamous and nonsquamous disease, respectively, the phase 3 EMPOWER-Lung 3 (NCT03409614)³ trial enrolled both histologies in a single trial and used histology-specific chemotherapy, allowing paclitaxel in nonsquamous disease. At 5 years, cemiplimab plus chemotherapy achieved a median OS of approximately 21.1 months compared with 12.9 months with chemotherapy alone (HR, 0.66; 95% CI, 0.53-0.83; P = .0002). Median progression-free survival was 8.2 vs 5.5 months (HR, 0.58; 95% CI, 0.47-0.72; P < .0001), and duration of response more than doubled. In the squamous subgroup, median OS reached 22.3 months (95% CI, 15.7-27.2) vs 13.8 months (95% CI, 9.3-18.0), compared with 18.4 months reported for pembrolizumab plus chemotherapy in KEYNOTE-407.⁴

Grade 3 or higher AEs occurred in approximately 50% of patients receiving cemiplimab plus chemotherapy, compared with approximately 70% for pembrolizumab plus chemotherapy and 60% for atezolizumab plus bevacizumab (Avastin; Genentech) and chemotherapy. Cass cautioned that these are cross-trial comparisons.⁴

“I think this is really interesting looking at these results, because we’re seeing better results with our squamous cell population—not typically what we are seeing among clinical trials. So, I think that that’s important to note here,” Cass said.

Real-World Use Lags the Data

Despite these results, participants said pembrolizumab remains the default option because of its familiarity and broad indications. Many view the class as interchangeable. Luon explained that his institution chose cemiplimab as its preferred PD-1 inhibitor years ago, but it did not stick. “We don’t use enough cemiplimab even though we made a decision many years ago that we would switch to cemiplimab as our preferred PD-1 inhibitor. We build plans, but doctors are creatures of habit.”

Conversely, the panelists noted that some payers are increasingly shifting that balance. Leila Rostamnjad, PharmD, BCOP, a clinical pharmacy manager at Dana-Farber Cancer Institute, in Boston, Massachusetts, said, “I would say at our institution pembro[lizumab] monotherapy or pembro plus chemo[therapy] is our go-to agent just because we have the longest experience with it. However, I have noticed recently that insurance companies are rejecting that combination in this squamous cell population… the monotherapy cemiplimab plus chemo, which of course we accept the recommendations.”

Despite the intention to prioritize cemiplimab-based regimens, she said that providers still gravitate to previously established therapeutic options. “We did adopt cemiplimab monotherapy [and] cemiplimab plus chemo in our pathways; however, our providers still choose pembro plus chemo.”

The panelists said that cemiplimab also fills a clinical niche in patients with nonsquamous disease and a creatinine clearance below 45 mL/min, for whom pemetrexed is not an option. Because EMPOWER-Lung 3 supports paclitaxel with cemiplimab regardless of histology, the regimen avoids peer-to-peer reviews that a paclitaxel-pembrolizumab plan often triggers. Cass emphasized, “I have kind of beat into them if bad kidney function, that cemiplimab is our option just to prevent issues down the road with insurance approval.”

The Pharmacist’s Role Varies by Practice Model

How involved pharmacists are in ICI selection depends heavily on the practice setting. In community oncology, pharmacists are often consulted on supportive care or formulary questions rather than regimen choice.

Brandon Dyson, PharmD, BCOP, BCPS, director of pharmacy education at Texas Oncology, explained, “The pharmacist role is clinical, but they simultaneously deal with the supportive care aspect, less of the treatment decision…but more of the antiemetics or whatever it might be, depending on the therapy.”

In other settings, pharmacists serve as a clinical check on every new regimen. Megan May, PharmD, BCOP, FHOPA, FAPO, an ambulatory oncology clinical pharmacy specialist at Baptist Health Lexington in Kentucky, said she and 3 colleagues educate every patient who is beginning oral or intravenous therapy at her institution, and they sit beside providers in clinic. She emphasized there must be open communication among health care professionals on the team to ensure that everyone is on the same page.

Pharmacists also carry much of the burden of access, Mitchell Blewett, PharmD, MS, BCOP, BCPS, director of oncology pharmacy at Cleveland Clinic in Ohio, said. He described daily prior-authorization huddles in which an interdisciplinary team decides when the institution will accept financial risk and treat before authorization is finalized.

Conclusion

Across all 3 roundtables, participants agreed that the clinical data alone do not determine which ICI a patient receives. Institutional pathways, payer policies, and long-standing prescriber familiarity with pembrolizumab continue to shape real-world selection. Testing delays, insurance denials, and gaps in outside records further complicate first-line decisions.

Oncology pharmacists sit at the center of these pressures. They build order sets and pathways, navigate prior authorizations, educate patients, and help providers match regimens to patient-specific factors such as renal function. As payers increasingly steer agent selection, participants emphasized that the oncology pharmacists’ ability to translate trial evidence into practical, approvable treatment plans will be essential to ensuring patients receive timely, appropriate immunotherapy.

REFERENCES

1. Study of REGN 2810 compared to platinum-based chemotherapies in participants with metastatic non-small cell lung cancer (NSCLC). ClinicalTrials.gov. Updated June 25, 2026. Accessed October 28, 2026. https://clinicaltrials.gov/study/NCT03088540

2. Kilickap S, Baramidze A, Sezer A, et al. Cemiplimab monotherapy for first-line treatment of patients with advanced NSCLC with PD-L1 expression of 50% or higher: five-year outcomes of EMPOWER-Lung 1. J Thorac Oncol. 2025;20(7):941-954. doi:10.1016/j.jtho.2025.03.033

3. Combinations of cemiplimab (anti-PD-1 antibody) and platinum-based doublet chemotherapy in patients with lung cancer. ClinicalTrials.gov. Updated May 18, 2026. Accessed October 28, 2026. https://clinicaltrials.gov/study/NCT03409614

4. Baramidze A, Makharadze T, Gogishvili M, et al. Cemiplimab plus chemotherapy versus chemotherapy in advanced NSCLC: 5-year results from phase 3 EMPOWER-Lung 3 part 2 trial. J Thorac Oncol. Published online June 15, 2026. doi:10.1016/j.jtho.2026.103980