IASLC World Conference on Lung Cancer 2022 — Meeting Report

Presenters at this year's meeting of the IASLC World Conference on Lung Cancer, held in Vienna, Austria, August 6–9, reported the latest research in lung cancer. NEJM Group covered the meeting, with guidance from NEJM Journal Watch Oncology and Hematology Associate Editor Jyoti D. Patel, MD, FASCO. Here are some highlights of that coverage.

The addition of nivolumab to neoadjuvant chemotherapy improved overall survival (OS) in patients with resectable stage IIIA–IIIB non–small-cell lung cancer (NSCLC), according to the phase 2 NADIM II trial.

In the open-label, randomized trial, 57 patients were assigned to receive neoadjuvant nivolumab (360 mg) plus paclitaxel plus carboplatin for three cycles every 21 days, followed by surgery, and 29 patients received the same regimen without nivolumab, followed by surgery. Patients in the nivolumab group with confirmed R0 resection then received adjuvant nivolumab (480 mg every 4 weeks) for 6 months.

At 24 months, the rate of pathologic complete response — the primary outcome — was 36% in the chemoimmunotherapy group versus 7% in the chemotherapy group. Survival outcomes also were significantly improved with chemoimmunotherapy compared with chemotherapy: progression-free survival (PFS) was 67% versus 53% (hazard ratio, 0.56) and OS was 85% versus 65% (HR, 0.37).

Patients in the chemoimmunotherapy group with PD-L1 expression ≥1% experienced the strongest PFS benefit (HR, 0.26). During up to 5 years of follow-up, no patient with pathologic complete response died or had disease progression.

Summary by Cara Adler, Staff Writer

COMMENT — JYOTI D. PATEL, MD, FASCO

The NADIM II study confirms that nivolumab in combination with neoadjuvant chemotherapy improves rates of pathologic complete response, complete resection, and survival compared with chemotherapy alone. It remains to be seen whether neoadjuvant chemoimmunotherapy or adjuvant immunotherapy is the most appropriate systemic therapy and whether the best local therapy for patients with stage III disease is surgery or radiation.

Read more about the study and watch our interview with the lead author of the study).

Adjuvant atezolizumab might improve overall survival in some patients with resected NSCLC whose tumors express PD-L1 on ≥% of cells, according to an interim secondary analysis from the industry-supported IMpower010 trial. An earlier interim analysis showed a statistically significant benefit for disease-free survival, the trial's primary outcome, with the drug.

In the phase 3, open-label trial, roughly 1000 patients with stage IB to IIIA NSCLC and PD-L1 expression ≥1% who had undergone resection and chemotherapy were randomized to atezolizumab (1200 mg every 21 days for 16 cycles or 1 year) or best supportive care. During a median follow-up of 45 months, 25% of patients died.

Among patients with stage II–IIIA disease, atezolizumab was associated with a 29% reduction in mortality, although this finding did not reach statistical significance (hazard ratio, 0.71; 95% CI, 0.49–1.03). The greatest benefit was seen among those with PD-L1 expression ≥50% (HR, 0.42; 95% CI, 0.23–0.78). A benefit was not observed among the entire study population of patients with stage IB to IIIA disease, however.

Summary by Amy Herman, Staff Writer

COMMENT — JYOTI D. PATEL, MD, FASCO

The interim analysis of overall survival from IMpower010 has been highly anticipated after adjuvant atezolizumab received approval for patients with resected stage II–IIIA NSCLC and PD-L1 tumor cells (TC) ≥1% last year based on improvements in disease-free survival. This new overall survival analysis shows a promising trend in favor of atezolizumab over best supportive care in the PD-L1 TC ≥1% stage II–IIIA population and most pronounced in the PD-L1 TC ≥50% stage II–IIIA population.

Read more about the study and watch our interview with the lead author).

Sublobar resection is noninferior to lobectomy for some patients with small-sized, peripheral NSCLC, according to an international, phase 3 trial.

Nearly 700 patients with peripheral NSCLC tumors ≤2 cm in size and confirmed node-negative status were intraoperatively randomized to lobar or sublobar resection. Randomization was stratified by smoking status, tumor size, and histology.

Minimally invasive resection approaches were used in 80% of patients overall. In the sublobar arm, wedge resection was performed in nearly 60%, segment resection in the rest.

At a median follow-up of 7 years, disease-free survival (DFS) — the primary outcome — was noninferior in the sublobar arm compared to the lobectomy arm, with a stratified hazard ratio of 0.999. At 5 years, DFS was 63.9% in the sublobar arm and 64.3% in the lobectomy arm. Overall survival also was noninferior in the sublobar arm, with a stratified hazard ratio of 0.930. Rates of disease recurrence did not differ between the two groups.

Summary by Cara Adler, Staff Writer

COMMENT — JYOTI D. PATEL, MD, FASCO

Sublobar resection in select patients with early stage, peripheral NSCLC can be considered a standard of care. Patients' overall survival was not impacted with limited resection and this approach offers an opportunity for preservation of lung function as well as treatment of second primary tumors in the future.

Read more about the study.

Nearly a third of adults who attended a lung screening event — where they began receiving smoking-cessation support — quit smoking within 3 months, according to a randomized trial from the U.K.

The trial included roughly 1000 smokers aged 55 to 80 who attended a lung health check event that included low-dose computed tomography (CT) screening, consultation with an onsite smoking-cessation professional, and arrangements for ongoing smoking-cessation support (e.g., behavioral support, pharmacotherapy). A month later, participants were randomized to add a personalized cessation intervention — which included receiving CT images of their heart and lungs, with emphysema and coronary artery calcifications highlighted — or to continue cessation support alone (control).

Three months after the lung health check event, the validated 7-day smoking abstinence rate was 34% in the intervention group and 30% in the control group, a nonsignificant difference. At 12 months, the abstinence rate was 29% in both groups.

In a subanalysis among women, the personalized intervention appeared more effective than standard support: 7-day abstinence was 34% versus 23%.

Summary by Amy Herman, Staff Writer

COMMENT — JYOTI D. PATEL, MD, FASCO

Many people who undergo lung cancer screening continue to smoke. Smoking cessation is the most effective way to reduce lung cancer mortality, and lung cancer screening is not a substitute for smoking cessation. Using the “teachable moment” during lung cancer screening for personalized smoking cessation that includes behavioral and pharmacologic support leads to high abstinence rates. All screening programs should include the best available and ongoing cessation support.

Read more about the trial.

Nearly a third of patients who were treated with sotorasib for NSCLC with KRAS^G12C mutations experienced significant hepatotoxicity, with the increased risk seemingly limited to those who had received immune checkpoint inhibitors (ICIs) in the prior 90 days, according to a small, retrospective study.

Researchers reviewed charts of 32 patients with NSCLC who had received sotorasib therapy at the Mayo Clinic in 2021. Ten patients (31%) developed grade 3 or higher hepatotoxicity.

Hepatotoxicity rates were as follows:

• For patients who received ICIs within the prior 30 days: 75%
• For those treated 31 to 90 days prior: 64%
• For those treated over 90 days prior: 0%
• For those without previous ICI exposure: 0%

After stopping sotorasib, all patients showed improvements in liver tests. Of eight patients who restarted sotorasib at a lower dose, five had to stop treatment when hepatotoxicity returned.

Summary by Kelly Young, Staff Writer

COMMENT — JYOTI D. PATEL, MD, FASCO

Although this is a small retrospective study, it offers important information for clinicians. The majority of patients with KRAS^G12C-mutated NSCLC will receive ICIs in the frontline setting, and recognizing this risk certainly will have clinical impact now — but also has relevance as we work to understand sequencing and combination of KRAS^G12C direct inhibitors and immunotherapy.

Read more about this study.

U.K. patients with NSCLC living in socioeconomically disadvantaged areas are less likely than their more affluent peers to receive novel anticancer treatments like targeted therapy and immunotherapy — a finding previously observed for more traditional therapies like chemotherapy and radiotherapy — according to an analysis of national health and demographic databases.

Researchers studied nearly 200,000 NSCLC cases diagnosed between 2012 and 2017; socioeconomic status was determined according to quintile of population income in the patient's residential area. After adjustment for age, sex, ethnicity, tumor stage, and other confounders, patients living in the most deprived areas were significantly less likely than those in the most affluent areas to receive any novel therapy (odds ratio, 0.54). Strong associations were seen for targeted therapies (OR, 0.40) and immunotherapies (OR, 0.58).

Significant associations persisted in subanalyses limited to patients with stage IV cancer, adenocarcinoma, or nonsquamous histology.

Summary by Amy Herman, Staff Writer

COMMENT — JYOTI D. PATEL, MD, FASCO

Novel biological and precision therapies and their associated predictive biomarker tests offer opportunities for increased tumor response, reduced adverse effects, and improved survival in patients with lung cancer. Unfortunately, there are significant inequities in access to these therapies, and it is incumbent upon us to reduce systemic barriers to access to improve care for all patients.

Read more about the study.