Case-Based Format Spotlights Hawaii Lung Cancer Conference

The rapidly changing treatment landscape of small cell and non-small cell lung carcinoma presented at the 2nd Annual Hawaii Lung: A Multidisciplinary Case-Based Conference™ will take advantage of the expertise and experience of local oncologists from Hawaii and mainland oncologists in a unique format.

“This is a very different structure from more traditional medical meetings,” Heather A. Wakelee, MD, FASCO, cochair of the conference and professor of medicine, University Medical Line, Department of Medicine – Oncology, Stanford University, Stanford, California, said in an interview with Targeted Therapies in Oncology. The cases used to illustrate clinical challenges, “highlight the teaching points that have been discussed during the most recent global conferences,” Wakelee continued. “The goal is to make sure we walk through all of the latest data, focusing on what is practical and practice changing.”

The format allows for a beneficial exchange of data by presenting the perspective not just of mainland oncologists explaining how they treat patients but also oncologists in the local community. “For some conferences, the draw is the speaker and in others, the audience gets talked at. We set out to avoid that [scenario]. This conference is set up to be more of an exchange because [we recognize that] there are practice differences around the country,” Wakelee said.

Attendees will find a diverse agenda awaiting them that addresses scenarios focused on screening, locally advanced disease, and advanced stage disease. Treatment scenarios that address driver mutations and those without driver mutations are on the agenda.

The multidisciplinary characteristics associated with optimal care, including radiation oncology and surgical oncology, will also be highlighted, Wakelee said.

“We will address neoadjuvant and adjuvant data and the perioperative trials that came out in 2023,” Wakelee said. Significant findings from a number of trials will make their way into case reports.

KEYNOTE-671

Results from KEYNOTE-671 (NCT03425643) showed that the perioperative approach of pembrolizumab (Keytruda) in patients with resectable stage II, IIIA or IIIB (T3-4N2) non–small cell lung cancer (NSCLC) met its dual primary end point of overall survival (OS) and event-free survival (EFS).¹

Treatment with neoadjuvant pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab as a single agent yielded a statistically significant and clinically meaningful improvement in OS vs neoadjuvant placebo plus chemotherapy followed by adjuvant placebo among this patient population.¹

A total of 786 patients were enrolled in the study and randomly assigned in a 1:1 ratio. In the first arm, patients were treated with pembrolizumab 200 mg intravenously (IV) every 3 weeks for up to 4 cycles with chemotherapy as neoadjuvant therapy prior to surgery, followed by pembrolizumab 200 mg IV every 3 weeks for up to 13 cycles as adjuvant therapy post-surgery. The second arm of the trial received placebo plus chemotherapy as neoadjuvant therapy prior to surgery, followed by placebo as adjuvant therapy post-surgery.¹

Investigators reported that median OS was not reached in patients treated with pembrolizumab (95% CI, not estimable [NE]-NE) and 52.4 months for those receiving placebo (95% CI, 45.7-NE) (HR, 0.72; 95% CI, 0.56-0.93; P = .0103). The median PFS was not reached in patients treated with pembrolizumab and 17 months in patients who received placebo (95% CI, 14.3-22.0) (HR, 0.58; 95% CI, 0.46-0.72; P < .0001).¹

In KEYNOTE-671, the most common adverse reactions reported in 20% or more patients were nausea, fatigue, neutropenia, anemia, constipation, decreased appetite, white blood cell count decreased, musculoskeletal pain, rash, cough, vomiting, diarrhea and dyspnea. Of the patients who received neoadjuvant treatment in the pembrolizumab arm, 6% were unable to receive surgery due to adverse reactions compared with 4.3% in the placebo arm. In addition, 3.1% of patients who received neoadjuvant treatment and surgery in the pembrolizumab arm had delays in surgery due to adverse reactions compared with 2.5% in the placebo arm.¹

The FDA approved pembrolizumab with platinum-containing chemotherapy as neoadjuvant treatment, and with continuation of single-agent pembrolizumab as postsurgical adjuvant treatment for resectable, defined as tumors 4 cm or greater, or node positive NSCLC, based on efficacy data from KEYNOTE-671.²

Checkmate 77T

Another perioperative trial, CheckMate 77T (NCT04025879), showed that neoadjuvant treatment with nivolumab (Opdivo) plus chemotherapy followed by surgery and adjuvant nivolumab led to an improvement in event-free survival (EFS) vs the control arm, which was placebo plus chemotherapy.³ Investigators reported that 461 patients were randomly assigned to receive either 360 mg of nivolumab and chemotherapy every 3 weeks (n = 229), followed by surgery and neoadjuvant therapy (n = 178), and 480 mg nivolumab every 4 weeks for 12 months (n = 142), or placebo and chemotherapy every 3 weeks for 4 cycles (n = 230). In this arm, patients then underwent surgery within 6 weeks of neoadjuvant therapy (n = 178), followed by placebo for 1 year (n = 152).³

Investigators reported that median EFS in patients in the treatment arm was not reached (NR; 95% CI, 28.9-NR), vs 18.4 months (95% CI, 13.6-28.1) in the control arm (HR, 0.58; 97.36% CI, 0.42-0.81; P = .00025).³

Patients in the treatment arm had a reduced risk of recurrence, progressive disease, or death by 44% compared with patients in the control arm (HR, 0.56; 95% CI, 0.41-0.76).³

Researchers reported that adverse events (AEs) related to surgery occurred in 73 (41%) patients in patients treated with nivolumab and 69 (39%) patients in the control arm. Twenty-one (12%) patients in each arm experienced grade 3 to 4 AEs.

Treatment-related deaths occurred in 2 (1%) patients in the nivolumab arm: 1 due to grade 5 pneumonitis and 1 due to grade 4 pneumonitis, both occurring after completion of neoadjuvant treatment.

ALK-Positive Disease

Findings from the phase 3 ALINA trial (NCT0345076) evaluated alectinib (Alecensa), an oral ALK inhibitor, compared with platinum-based chemotherapy across all prespecified subgroups in patients with early stage ALK positive NSCLC in the phase 3 ALINA trial (NCT0345076).⁴

Patients with stage II-IIIA who received alectinib (n = 116) had a 76% reduced risk of disease recurrence or death (HR, 0.24; 95% CI, 0.13-0.45; P < .0001), compared with those who received platinum-based chemotherapy (n = 115). Among these 2 groups, the median disease-free survival (DFS) was not reached (95% CI, 28.5-[NE) with alectinib vs 44.4 months (95% CI, 27.8-NE) with chemotherapy.⁴

“The trial showed that by giving alectinib for 2 years, you have a significant disease-free survival benefit versus chemotherapy,” Wakelee said.

“We know that a patient with metastatic lung cancer getting alectinib is likely to still be doing well with it at two years,” she continued.

Regarding toxicity and safety, the rate of grade 3 or 4 adverse events (AEs) was similar between the 2 groups: 30% and 31% of patients receiving targeted or chemotherapy, respectively, reported high-grade AEs. No grade 5 events were reported in either cohort.⁴

The rate of any-grade AEs was 98% vs 93%, respectively. Of note, a higher percentage of patients receiving alectinib needed to dose reduce because of an AE (26% vs 10%) or interrupt treatment because of an AE (27% vs 18%), although fewer needed to discontinue treatment overall (5% vs 13%).⁴

“The treatment paradigm in lung cancer is rapidly evolving. It’s an exciting time because we have more treatment options to offer our patients,” Wakelee said. “It should be a great meeting to talk about what does all the data mean in the context of treating a patient and how to make treatment decisions based on these new data,” she concluded.

REFERENCES:

1. Wakelee H, Liberman M, Kato T, et al. Perioperative Pembrolizumab for early-stage non-small-cell lung cancer. N Engl J Med. 2023;389(6):491-503. doi:10.1056/NEJMoa2302983

2. FDA. FDA approves neoadjuvant/ adjuvant pembrolizumab for resectable non-small cell lung cancer. News release. October 16, 2023. Accessed November 14, 2023. https:// tinyurl.com/2k3n4bfr

3. Cascone T, Awad MM, Spicer J, et al. CheckMate 77T: Phase 3 study comparing neoadjuvant nivolumab plus chemotherapy with neoadjuvant placebo plus chemotherapy followed by surgery and adjuvant nivolumab or placebo for previously untreated, resectable stage II–IIIB NSCLC. Ann Oncol. 2023;34(suppl 2):S1295. doi:10.1016/j. annonc.2023.10.050

4. Solomon BJ, Ahn, JS, Dziadziuszko R, et al. Efficacy and safety of adjuvant alectinib versus chemotherapy in patients with early-stage ALK+ non-small cell lung cancer (NSCLC). Ann Oncol. 2023;34(suppl 2):LBA2.