Manish Patel, DO, hematologist, oncologist, associate professor of medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, discusses updates in treatment with a PD1 and CTLA-4 inhibitor in non–small cell lung cancer (NSCLC)

The phase 3 EMPOWER-Lung 3 trial (NCT03409614), studying cemiplimab-rwlc (Libtayo) with chemotherapy, produced positive data similar to the phase 3 KEYNOTE-189 trial (NCT02578680), which evaluated pembrolizumab (Keytruda) plus chemotherapy, Patel explains. Notably, EMPOWER-Lung 3 demonstrated a particular benefit in patients with squamous cell NSCLC, Patel adds.

Additionally, data from the phase 3 POSEIDON trial (NCT03164616) supported 

the FDA approval of durvalumab (Imfinzi) and tremelimumab-actl (Imjudo) with platinum-based chemotherapy

 for the treatment of adult patients with metastatic NSCLC without sensitizing 

aberrations, Patel continues. POSEIDON was another example of a trial showing the benefit of treating patients with chemotherapy in combination with a PD-1 inhibitor and CTLA-4 inhibitor, Patel concludes.

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Manish Patel, DO, discusses updates in treatment with a PD1 and CTLA-4 inhibitor in non–small cell lung cancer.


Dr. Patel on Key Updates from First-Line Trials in NSCLC

Manish Patel, MD, DO, hematologist, oncologist, associate professor of medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, discusses choosing a chemoimmunotherapy regimen for patients with advanced, metastatic non–small cell lung cancer (NSCLC). 

The phase 3 CheckMate 9LA trial (NCT03215706) evaluates chemotherapy plus nivolumab (Opdivo) and ipilimumab (Yervoy), providing patients with an alternative to pembrolizumab (Keytruda) plus chemotherapy, Patel says. Current data for each regimen suggest that there are similar efficacy outcomes and toxicity profiles for each of these regimens, Patel adds. However, the absence of head-to-head comparative studies makes the decision challenging, Patel continues.

Treatment selection should account for both updated efficacy results and individual patient factors, Patel continues. For example, patients who are reluctant to undergo chemotherapy may benefit more from the CheckMate 9LA regimen, Patel says. Alternatively, the known reliability and efficacy of pembrolizumab plus chemotherapy continue to support its use as a standard-of-care regimen, Patel notes.

Ultimately, both regimens are viable treatment options for patients with NSCLC, Patel concludes.

Manish Patel, MD, DO, discusses choosing a chemoimmunotherapy regimen for patients with advanced, metastatic non–small cell lung cancer.  

Dr. Patel on Choosing a Chemoimmunotherapy Treatment in NSCLC

Manish Patel, DO, hematologist, oncologist, associate professor of medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, discusses the role of CTLA-4 inhibitors in non–small cell lung cancer (NSCLC).

Although it is difficult to determine when to include a CTLA-4 inhibitor in treatment regimens for patients with NSCLC, the chemotherapy-free option of nivolumab (Opdivo) plus ipilimumab (Yervoy) is preferable in some cases compared with chemotherapy, Patel explains. If a patient has PD-L1–negative disease or intermediately expresses PD-L1, the nivolumab plus ipilimumab combination could mitigate chemotherapy-related toxicities, Patel explains. However, it can be sometimes difficult to determine which patients require chemotherapy and who will benefit from the addition of a CTLA-4 inhibitor without significant toxicity, Patel adds.

 Being able to understand which patients will benefit from the combination will spare many patients from unnecessary toxicities and will be cost-effective for health care overall, Patel continues. Moreover, identifying which patients do not require chemotherapy up front will guide treatment decisions, Patel concludes.

Manish Patel, DO, discusses the role of CTLA-4 inhibitors in non–small cell lung cancer. 

Dr. Patel on the Role of CTLA-4 Inhibitors in NSCLC

Manish R. Patel, DO, associate professor of medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, discusses the safety profile of entrectinib (Rozlytrek) in 

 of the STARTRK01, STARTRK-2, and ALKA-372-001 studies were presented during the 

2020 ESMO World Congress on Gastrointestinal Cancers

. These trials evaluated the role of entrectinib in 

 fusion–positive cancers, including breast cancer, cholangiocarcinoma, colorectal cancer, gynecological cancer, non–small cell lung cancer, pancreatic cancer, and thyroid cancer. 

Regarding safety, NTRK inhibitors have been associated with neural network involvement that can cause adverse effects (AEs) such as dizziness and taste change, Patel explains. 

While AEs were observed in the patients who were evaluated for safety, no unexpected toxicities were noted with the agent in this analysis, says Patel. Moreover, the toxicities that were observed were mostly grade 1 or 2 and resolved or improved with dose reductions or dose interruptions. 

One patient required discontinuation from treatment. Additionally, 2 treatment-related deaths were reported on the study; however, they were not confirmed to be related to entrectinib, concludes Patel. 

Manish R. Patel, DO, discusses the safety profile of entrectinib in NTRK fusion–positive solid tumors.  



Dr. Patel on the Safety Profile of Entrectinib in NTRK+ Solid Tumors 

Manish R. Patel, DO, associate professor of medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, discusses the role of entrectinib (Rozlytrek) in gastrointestinal (GI) malignancies.

At the 2020 ESMO World Congress on GI Cancer, findings from an updated integrated analysis of the STARTRK-1, STARTRK-2, and ALKA-372-001 studies evaluating entrectinib in 

 fusion–positive GI cancers were presented.

Entrectinib is a pan-TRK, ROS1, and ALK inhibitor that received FDA approval in August 2019 for the treatment of patients with solid tumors that harbor an 

-positive metastatic non–small cell lung cancer.

Additionally, entrectinib is a well-tolerated agent, says Patel.

 fusions are relatively uncommon in GI cancers, entrectinib could be an effective option for patients with these actionable alterations, concludes Patel.

Manish R. Patel, DO, discusses the role of entrectinib in gastrointestinal malignancies.



Dr. Patel on the Role of Entrectinib in Gastrointestinal Malignancies

Manish R. Patel, DO, associate professor of medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, discusses choosing immunotherapy drugs for patients with non—small cell lung cancer (NSCLC).

The immunotherapy drugs available to treat NSCLC are virtually the same in terms of toxicity, according to Patel. Phase III trials with atezolizumab (Tecentriq), nivolumab (Opdivo), and pembrolizumab (Keytruda) show that the rate of immune-related adverse events (AEs) are virtually identical with few percentage point differences between them, explains Patel.

Additionally, the efficacy is very similar, with little differences based on PD-L1 expression versus tumor mutational burden, says Patel. Virtually none of the drugs have off-target effects, which makes the AEs more immune-related rather than other off-target toxicities. Patel views the available immunotherapy drugs as the same, making it difficult for him to say one is superior to the other.

Manish R. Patel, DO, discusses choosing immunotherapy drugs for patients with non–small cell lung cancer.

Dr. Patel on Choosing Immunotherapy Drugs for NSCLC

Manish R. Patel, DO, hematologist/oncologist, Masonic Cancer Clinic, discusses current questions and research regarding immunotherapy in non—small cell lung cancer (NSCLC).

Currently, there are 2 FDA-approved first-line chemoimmunotherapy regimens, which comprise pembrolizumab (Keytruda) with chemotherapy as well as a 4-drug regimen comprising atezolizumab (Tecentriq), bevacizumab (Avastin), and carboplatin/paclitaxel. Currently, it is hard to know who might benefit from the addition of bevacizumab, explains Patel. Patients with liver metastases or patients with 

 mutations who have failed TKIs seem to benefit from bevacizumab, according to Patel.

In order to understand why bevacizumab might help with response to immunotherapy, Patel believes physicians need to gather more data about the immunologic effects of VEGF-targeted therapy and trying to understand what patients might benefit the most.

Results of the KEYNOTE-024 trial showed that patients with NSCLC and high PD-L1 expression benefit from pembrolizumab monotherapy compared with chemotherapy alone. However, an unanswered question is whether combination of chemotherapy and immunotherapy is beneficial compared with immunotherapy alone in that patient population. Some ongoing studies will help answer those questions, Patel concludes.

Manish R. Patel, DO, discusses current questions and research regarding immunotherapy in non–small cell lung cancer.

Manish R. Patel, DO

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