Justin F. Gainor, MD, director of Targeted Immunotherapy, Massachusetts General Hospital, and assistant professor of medicine, Harvard Medical School, discusses the evolving lung cancer armamentarium.

Following the recognition that lung cancer is a heterogeneous disease, the field has evolved dramatically, says Gainor. The disease is now defined by different genetic alterations as well as oncogenic drivers.

Notably, in recent years, several targeted therapies have received regulatory approval for 7 molecular alterations in this space.

Ultimately, these approvals created a rich environment for targeted therapies and underscored the importance of genetic profiling, especially when it comes to administering optimal therapies to patients with newly diagnosed lung cancer, Gainor concludes.

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Justin F. Gainor, MD, discusses the evolving lung cancer armamentarium.

Dr. Gainor on the Evolving Lung Cancer Armamentarium 

Justin F. Gainor, MD, director of Targeted Immunotherapy, Massachusetts General Hospital, and assistant professor of medicine, Harvard Medical School, discusses a neoadjuvant use of biomarkers in nonmetastatic lung cancer.

There is intense interest in trying to understand biomarkers of response to checkpoint inhibitors, says Gainor. One of the key avenues to understanding the mechanisms of response to checkpoint inhibitors is through tissue. By gathering a sample of tissue from the tumor site, physicians are able to see whether or not there are specific genomic markers present and what is occurring in the immune microenvironment.

A neoadjuvant approach allows investigators to obtain tissue before and after treatment to determine how the tumor has changed in response to therapy. This is one of the reasons why there has been some enthusiasm for the neoadjuvant approach of biomarkers because it allows investigators to obtain more tissue, concludes Gainor.

Justin F. Gainor, MD, discusses a neoadjuvant use of biomarkers in nonmetastatic lung cancer.
 

Dr. Gainor on Neoadjuvant Use of Biomarkers in Nonmetastatic Lung Cancer

Justin F. Gainor, MD, director of Targeted Immunotherapy, Massachusetts General Hospital, and assistant professor of medicine, Harvard Medical School, discusses neoadjuvant checkpoint blockade in non—small cell lung cancer (NSCLC).

At the 2019 ASCO Annual Meeting, several studies were presented on the use of neoadjuvant checkpoint blockade. The first was the Lung Cancer Mutation Consortium (LCMC) study, which looked at neoadjuvant and adjuvant atezolizumab (Tecentriq). Notably, a subset of patients had disease progression prior to surgery; several others experienced disease progression or unresectable disease at the time of surgery. However, the majority of patients were able to undergo surgical resection; those patients tended to have stage I/II disease, says Gainor.

Additionally, a study conducted by investigators at The University of Texas MD Anderson Cancer Center evaluated the use of single-agent nivolumab (Opdivo) versus the combination of nivolumab and ipilimumab (Yervoy) as induction therapy. Data showed that the combination of nivolumab and ipilimumab resulted in a slightly higher major pathologic response rate than was seen in the LCMC trial.

Justin F. Gainor, MD, director of Targeted Immunotherapy, Massachusetts General Hospital, and assistant professor of medicine, Harvard Medical School, discusses neoadjuvant checkpoint blockade in non–small cell lung cancer (NSCLC).

Dr. Gainor on Neoadjuvant Checkpoint Blockade in NSCLC

Justin F. Gainor, MD, director of Targeted Immunotherapy, Massachusetts General Hospital, and assistant professor of medicine, Harvard Medical School, discusses subgroup analyses from the phase III PACIFIC trial in unresectable stage III non—small cell lung cancer (NSCLC).

In addition to looking at the primary endpoints of the trial, it's also important to address key subgroups. In terms of PD-L1 expression, the subgroup with higher PD-L1 expression, which in PACIFIC was defined as ≥25%, tended to have better rates of progression-free survival (PFS) and overall survival. In patients who had lower PD-L1 expression, there was still an improvement in PFS, but not to the same degree, says Gainor. Although these data provide additional context, the standard of care in the United States is durvalumab (Imfinzi) regardless of PD-L1 expression.

Another important subset that did not seem to derive the same degree of benefit were 

-mutant patients. In the stage IV setting, 

-mutant patients do not derive significant benefits from single-agent immunotherapy. The same appears to be true in this setting, adds Gainor.

Furthermore, investigators did an analysis looking at time to initiation of durvalumab after chemoradiation. Patients who started durvalumab within 14 days had better outcomes compared with those who started after that 14-day time period. However, there are many caveats to the analysis. Therefore, a patient who has not fully recovered yet from chemoradiation within 14 days should not feel obligated to start durvalumab within that time frame, concludes Gainor.

Justin F. Gainor, MD, director of Targeted Immunotherapy, Massachusetts General Hospital, and assistant professor of medicine, Harvard Medical School, discusses subgroup analyses from the phase III PACIFIC trial in unresectable stage III non–small cell lung cancer (NSCLC).

Dr. Gainor on Subgroup Analyses From the PACIFIC Trial in NSCLC

Justin F. Gainor, MD, director of Targeted Immunotherapy, Massachusetts General Hospital, assistant professor of medicine, Harvard Medical School, discusses the phase III PACIFIC-2 trial in stage III non—small cell lung cancer (NSCLC).

With the PACIFIC-2 trial, investigators are trying to answer the question of whether concurrent delivery of immunotherapy is better than sequential delivery in patients with stage III unresectable NSCLC. In the trial, patients will be randomized to receive either platinum doublet chemotherapy plus radiation plus durvalumab (Imfinzi) followed by durvalumab consolidation or chemotherapy plus radiation followed by placebo consolidation.

Concurrent chemotherapy and radiation is better than sequential chemotherapy and radiation, says Gainor, but whether concurrent chemoradiation and immunotherapy is better than consolidative immunotherapy remains to be seen. The trial could go either way, he adds. Although it is known that radiation has profound effects on the immune system, the effects may be negated if both modalities are given at the same time. Notably, the control arm does not reflect the current standard of care, which will make it difficult to adapt to the current paradigm.

Justin F. Gainor, MD, director of Targeted Immunotherapy, Massachusetts General Hospital, assistant professor of medicine, Harvard Medical School, discusses the phase III PACIFIC-2 trial in stage III non–small cell lung cancer (NSCLC).

Dr. Gainor on the PACIFIC-2 Trial in Stage III NSCLC

Justin F. Gainor, MD, assistant professor of medicine, Harvard Medical School, attending physician, Massachusetts General Hospital, discusses the future of treatment for patients with 

-positive non-small cell lung cancer (NSCLC).

The results of FLAURA are convincing enough to suggest that osimertinib (Tagrisso) should be first-line treatment of choice for these patients, says Gainor.

Moving forward, better understanding response and resistance to osimertinib should be a priority, Gainor adds.

Justin F. Gainor, MD, assistant professor of medicine, Harvard Medical School, attending physician, Massachusetts General Hospital, discusses the future of treatment for patients with EGFR-positive non-small cell lung cancer.

Justin F. Gainor, MD

Articles

Dr. Gainor on the Evolving Lung Cancer Armamentarium

Dr. Gainor on Neoadjuvant Use of Biomarkers in Nonmetastatic Lung Cancer

Dr. Gainor on Neoadjuvant Checkpoint Blockade in NSCLC

Dr. Gainor on Subgroup Analyses From the PACIFIC Trial in NSCLC

Dr. Gainor on the PACIFIC-2 Trial in Stage III NSCLC

Dr. Gainor Discusses the Future of EGFR+ NSCLC