Two ASCO guideline updates provide new evidence-based recommendations for the systemic treatment of stage IV non–small cell lung cancer (NSCLC) with and without driver alterations.1,2 Among several other updates, these new guidelines add the ALK and ROS1 inhibitor lorlatinib and the PD-L1 immune checkpoint inhibitor atezolizumab to the treatment landscape for these patient populations.
Navneet Singh, MD, DM
According to Navneet Singh, MD, DM, of the Postgraduate Institute of Medical Education and Research in Chandigarh, India, and Co-Chair of the guideline expert panel, the updates came about because of the “rapidity of available data from clinical trials subsequent to the” ASCO guidelines on systemic therapy for stage IV NSCLC with and without driver alterations in 2021 and 2020, respectively.3,4
When asked to comment on the guideline, Co-Chair of the guideline expert panel Ishmael A. Jaiyesimi, DO, of Beaumont Health, said the newly updated recommendations are based on “potentially practice-changing evidence” that offers important beneficial implications for patient outcomes.
Updated Recommendations: Stage IV NSCLC With Driver Alterations
According to Dr. Jaiyesimi, the previous guideline on stage IV NSCLC with driver alterations recommended alectinib or brigatinib as first-line therapies for patients with stage IV NSCLC harboring ALK rearrangements.3 In the most recent update, lorlatinib has been added as an alternative first-line ALK inhibitor for these patients.1 The new recommendation incorporates data from the CROWN trial, which compared lorlatinib with crizotinib as a first-line treatment of patients with metastatic NSCLC who harbored an ALK fusion/rearrangement.5
“Based on the CROWN trial, lorlatinib becomes another option that may be offered [for] the treatment of patients with ALK-positive stage IV NSCLC,” Dr. Singh said. This recommendation effectively increases the number of drugs available to five treatments: alectinib, brigatinib, ceritinib, crizotinib, and now lorlatinib.
Dr. Singh noted the choice of therapy should be based on several different systems-, clinical-, and patient-related factors.
“[The final decision] has to be [made] by patients and their caregivers in consultation with the treating oncologist based on drug availability, efficacy, and side effect profile,” he said.
The updated recommendations also cover the use of selpercatinib and pralsetinib among patients with stage IV NSCLC who harbor RET fusion/-rearrangement.1
Updated Recommendations: Stage IV NSCLC Without Driver Alterations
The updated guideline on the treatment of patients with stage IV NSCLC without oncogenic driver alterations now recommends atezolizumab as another immunotherapy for previously untreated patients with high PD-L1 expression of 50% or greater.2 Data from the IMpower110 trial were used to inform this updated guideline recommendation.6
The guideline states that clinicians may offer single-agent atezolizumab, single-agent cemiplimab, a combination of nivolumab and ipilimumab without chemotherapy, or a combination of nivolumab and ipilimumab with two cycles of platinum-based chemotherapy. These recommendations, however, vary based on PD-L1 expression.2
Dr. Jaiyesimi said that, for patients with low–PD-L1 lung cancer, the addition of nivolumab and ipilimumab without chemotherapy as a possible alternative approach may permit some patients to avoid chemotherapy toxicities. The inclusion of more treatment options in the updated guideline may also provide improved opportunities for shared decision-making, among other benefits.
“For instance, the increased list of acceptable first-line options may help physicians if they run into situations where their preferred first-line option is not available and allow patients and family to participate in decision-making,” Dr. Jaiyesimi said.
Dr. Jaiyesimi explained that patients with NSCLC are living longer now than they were just a decade ago, which can be largely attributed to new drug advancements. The extended lifespan in this population has also provided an opportunity to enroll more patients in novel clinical trials, which Dr. Jaiyesimi hopes may improve future clinical outcomes for this patient population.
“Physicians should simultaneously continue to stress cancer clinical trials participation among all our patients and be on the lookout for the latest updates,” he said.
When asked about the clinical implications of the updated guidelines, Dr. Singh indicated the new recommendations “should serve as a ready reckoner for practicing clinicians in a wide variety of geographic locations and work settings to select the most effective and appropriate treatment option for patients with stage IV NSCLC.” But additional iterations of the guidelines are likely already on the horizon, given the rapidly evolving nature of the research focused on newer and novel targeted agents for stage IV NSCLC.
“Future updates are likely to be needed sooner [rather] than later as a continuous process rather than a periodic effort,” Dr. Singh added.
With the availability of multiple effective treatment options for stage IV NSCLC with and without oncogenic driver alterations, Dr. Singh speculates that future research and clinical trials for the disease will be focused on defining the optimal sequencing strategies for specific subgroups. These clinical trials will provide further refinements to future guideline updates.
Dr. Jaiyesimi added that the ASCO panel is also excited about phase III trials comparing targeted agents with docetaxel in the second-line setting for stage IV NSCLC with driver alterations.
1. Singh N, Temin S, Baker Jr S, et al: Therapy for stage IV non-small-cell lung cancer with driver alterations: ASCO living guideline. J Clin Oncol. July 11, 2022 (early release online).
2. Singh N, Temin S, Baker Jr S, et al: Therapy for stage IV non-small-cell lung cancer without driver alterations: ASCO living guideline. J Clin Oncol. July 11, 2022 (early release online).
3. Hanna NH, Robinson AG, Temin S, et al: Therapy for stage IV non-small-cell lung cancer with driver alterations: ASCO and OH (CCO) joint guideline update. J Clin Oncol 39:1040-1091, 2021.
4. Hanna NH, Schneider BJ, Temin S, et al: Therapy for stage IV non-small-cell lung cancer without driver alterations: ASCO and OH (CCO) joint guideline update. J Clin Oncol 38:1608-1632, 2020.
5. Shaw AT, Bauer TM, de Marinis F, et al: First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer. N Engl J Med 383:2018-2029, 2020.
6. Herbst RS, Giaccone G, de Marinis F, et al: Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. N Engl J Med 383:1328-1339, 2020.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, July 12, 2022. All rights reserved.