HOPA 2021: New Therapies on the Horizon for Advanced NSCLC

A session at the Hematology/Oncology Pharmacy Association Virtual Annual Conference provided an overview of how treatment options are changing with potential new therapies in development for patients with non-small cell lung cancer.

The treatment landscape for non-small cell lung cancer (NSCLC) shows an increasing number of options for patients and care providers. In a session of the Hematology/Oncology Pharmacy Association Virtual Annual Conference, Michelle A. Worst, PharmD, BCOP, MBA, presented an overview of how treatment options are changing with potential new therapies in development for patients with NSCLC.

According to 2021 data cited by Worst from the National Comprehensive Cancer Network, lung cancer is the leading cause of cancer death among men and NSCLC accounts for 80% of all lung cancers, with adenocarcinoma the most common.

Worst’s presentation primarily focused on systemic treatments for patients with stage IV NSCLC. These treatments include chemotherapy, immunotherapy, targeted therapy, or a combination of these therapies.

“In general, the goal at this stage is palliation,” she said.

In her presentation, Worst noted that the treatment landscape for NSCLC has dramatically changed in recent years. She noted that NSCLC treatment has developed at a rapid pace in the past decade with more FDA approvals in the past 10 years alone than in the previous century. She noted that in 2020, there were 11 new approvals in the NSCLC space.

“It truly has been a big bang,” Worst said.

Referencing a few FDA approvals already announced this year, Worst also forecasted that 2021 could be even more monumental for NSCLC than 2020.


Worst first addressed immune checkpoint inhibitors (ICIs) for front-line advanced NSCLC, which are being used alone or in combination with other therapies.

“Immunotherapy has proven to be a safe and efficacious treatment option for a variety of tumors and is often used in front-line settings,” she said.

Recent studies have demonstrated support of treatment guidelines for patients with programed death-ligand 1 (PD-L1) > 1% and initial systemic therapy options containing immunotherapy. These treatments include nivolumab and ipilmumab; a combination of nivolumab and ipilmumab with pemetrexed and carboplatin or cisplatin for patients with non-squamous disease; and carboplatin, paclitaxel, nivolumab, and ipilimumab for patients with squamous disease.

Worst also highlighted several emerging immunotherapy options for NSCLC, but noted that those featured in her presentation are only a portion of the potential therapies being investigated.

Promising emerging immunotherapies include cemiplimab for advanced NSCLC and PD-L1 > 50%: 1L, which was approved by the FDA in February 2021; and tislelizumab, and sintilimab, both for advanced squamous NSCLC: 1L.

Targeted Therapies

As precision-based therapies improve treatment outcomes and quality of life compared to traditional chemotherapy, Worst said that knowledge of pathways, technologies for detecting actionable mutations, and newly developed drugs are allowing care providers to better personalize treatments for their patients.

Although a number of targeted therapies are being used for eligible patients with advanced NSCLC, Worst highlighted a few with recent studies that support their use. These include erlotinib plus ramucirumab, brigatinib, capmatinib, selpercatinib, and pralsetinib.

Brigatinib, for example, was approved by the FDA in May 2020 with a companion diagnostic. Worst presented results from the ALTA-1L trial (NCT02737501) that demonstrated the efficacy of brigatinib versus crizotinib. The overall response rate was 74% for brigatinib and 62% for crizotinib.

“Progression-free survival was significantly better for those that received brigatinib versus crizotinib at 24 months and 11 months, respectively,” Worst said.

However, overall survival was similar between the 2 therapies, with 76% for brigatinib and 74% for crizotinib.

According to Worst, other emerging targeted therapies with promising study data include lorlatinib, tepotinib, trastuzumab deruxtecan, sotorasib, and osimertinib.


Worst said the use of immunotherapy in NSCLC has consistently improved outcomes in patients and continues to evolve. Additionally, molecular alterations in NSCLC are vast with more on the horizon, but ensuring patients receive adequate profiling is critical to improving their outcomes.


Worst M. The modern-day big bang: expanding horizons in the management of advanced non-small cell lung cancer. Presented at: Hematology/Oncology Pharmacy Association Virtual Annual Conference. April 13-17, 2021.