Naiyer A. Rizvi, MD, Price Family ​Professor of ​Medicine, director of Thoracic Oncology, and co-director of Cancer Immunotherapy at Herbert Irving Comprehensive Cancer Center, of Columbia University Medical Center, as well as research director at the Price Family Comprehensive Center for Chest Care of New York-Presbyterian Hospital, discusses the clinical implications of the CheckMate-227 trial examining the use of nivolumab (Opdivo) plus ipilimumab (Yervoy) in the treatment of patients with non–small cell lung cancer (NSCLC).

Data from the CheckMate-227 trial demonstrated that the combination elicited compelling responses, as well as an improvement in progression-free survival and overall survival in patients with NSCLC, according to Rizvi. In the trial, patients were administered 3 mg/kg of nivolumab every 2 weeks and 1 mg/kg of ipilimumab every 6 weeks. The combination was found to yield benefit across patients with varying degrees of PD-L1 expression, with some demonstrating deep responses, Rizvi explains.

Additionally, the combination appeared to be well tolerated, which is promising, according to Rizvi, as there is some concern with toxicities related to treatment with ipilimumab, particularly in patients who receive the 1-mg/kg dose, says Rizvi. The May 2020 

FDA approval of nivolumab/ipilimumab for select patients with metastatic NSCLC

 represents a positive development in the NSCLC treatment paradigm, Rizvi concludes.

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Naiyer A. Rizvi, MD, discusses the clinical implications of the CheckMate-227 trial examining the use of nivolumab plus ipilimumab in the treatment of patients with non–small cell lung cancer.

Dr. Rizvi on the Implications of the CheckMate-227 Trial With Nivolumab/Ipilimumab in NSCLC

Naiyer A. Rizvi, MD, Price Family ​Professor of ​Medicine; director of Thoracic Oncology; and co-director of Cancer Immunotherapy at Herbert Irving Comprehensive Cancer Center, of Columbia University Medical Center, as well as the research director at the Price Family Comprehensive Center for Chest Care of NewYork-Presbyterian Hospital, discusses the use of biomarkers to select patients with non–small cell lung cancer (NSCLC) for treatment with immunotherapy.

Tumor mutational burden (TMB) can be a useful tool to select patients with NSCLC who should receive immunotherapy, according to Rizvi. Pembrolizumab (Keytruda) monotherapy, for example, was

 for patients with unresectable or metastatic solid tumors with a high TMB of 10 mutations per megabase or higher who have progressed after previous therapy and who have no satisfactory available therapeutic options. There is also some interest in trying to identify patients with NSCLC who are positive for both PD-L1 expression and TMB, as this subset may be more likely to respond to PD-1 monotherapy, explains Rizvi.

Patients who have a PD-L1 expression of 50% or higher are generally treated with pembrolizumab monotherapy, although retrospective data with the agent and additional data with cemiplimab (Libtayo) indicate that different PD-L1 levels can impact response to treatment. For example, patients with a PD-L1 expression of 90% or higher are more likely to benefit from a PD-1 monotherapy versus someone with a PD-L1 expression of 50% to 60%, according to Rizvi.

 are most commonly observed in these patients and they have been shown to be associated with poor prognosis and potential resistance to immunotherapy, adds Rizvi. Some approaches may help to actively address these specific mutations, such as epigenetic modifiers, concludes Rizvi.

Naiyer A. Rizvi, MD, discusses the use of biomarkers to select patients with non–small cell lung cancer for treatment with immunotherapy.

Dr. Rizvi on Biomarkers of Response to Immunotherapy in NSCLC

Naiyer A. Rizvi, MD, Price Family ​Professor of ​Medicine, director, Thoracic Oncology, co-director, Cancer Immunotherapy, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, research director, Price Family Comprehensive Center for Chest Care, NewYork-Presbyterian Hospital, discusses the rationale to evaluate the investigational glutaminase inhibitor telaglenastat (CB-839) in patients with non–small cell lung cancer (NSCLC) who harbor 

-mutant tumors are thought to be highly proliferative and largely dependent on glutamine to complete anabolic metabolism, says Rizvi. Moreover, fast-growing tumors have significant anabolic metabolism requirements. These requirements can be dependent on glucose or glutamine, depending on the body’s anabolic state.

Glutamine is metabolized to glutamate for DNA protein synthesis, Rizvi explains. Additionally, glutamine is converted to glutathione, which can protect cancer cells from oxidative stress, says Rizvi. 

As such, preclinical models with telaglenastat in patients with 

-mutant NSCLC have shown that inhibiting glutamine metabolism with an agent such as telaglenastat can increase the oxidative stress within the cancer cells. Giving telaglenastat in combination with standard of care options, such as pembrolizumab (Keytruda), carboplatin, and pemetrexed, may elicit improved tumor destruction, concludes Rizvi.

Naiyer A. Rizvi, MD, discusses the rationale to evaluate the investigational glutaminase inhibitor telaglenastat in patients with non–small cell lung cancer who harbor KEAP1 or NRF2 mutations.  



Dr. Rizvi on the Rationale to Evaluate Telaglenastat in KEAP1/NRF2-Mutant NSCLC 

Naiyer A. Rizvi, MD, Price Family ​Professor of ​Medicine, director, Thoracic Oncology, co-director, Cancer Immunotherapy, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, research director, Price Family Comprehensive Center for Chest Care, NewYork-Presbyterian Hospital, discusses the utility of fam-trastuzumab deruxtecan-nxki (Enhertu) in non–small cell lung cancer (NSCLC).


Trastuzumab deruxtecan has demonstrated impressive clinical activity with modest myelosuppression and toxicities in patients with pretreated NSCLC, says Rizvi. 

, trastuzumab deruxtecan induced a confirmed objective response rate of 61.9%, includ​ing a 2.4% complete response rate, a 59.5% partial response rate, and a 28.6% stable disease rate.

Future research should explore this agent in the first-line setting as a single agent and a combination therapy, Rizvi concludes.

Naiyer A. Rizvi, MD, discusses the utility of fam-trastuzumab deruxtecan-nxki  in non–small cell lung cancer. 

Dr. Rizvi on the Utility of Trastuzumab Deruxtecan in NSCLC 

Naiyer A. Rizvi, MD, Price Family ​Professor of ​Medicine, director, Thoracic Oncology, co-director, Cancer Immunotherapy, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, research director, Price Family Comprehensive Center for Chest Care, NewYork-Presbyterian Hospital, discusses treatment approaches in non–small cell lung cancer (NSCLC). 

​Therapy for patients with NSCLC should be individualized ​and selected based on molecular ​abnormalities and PD-L1 status, says Rizvi.

However, patients with high PD-L1 expression and an 

 mutation should receive targeted therapy rather than immunotherapy as oncogenic drivers are preferred to PD-L1 status, Rizvi explains. 

Moreover, in an era where numerous plasma​-based assays are receiving regulatory approval, molecular data should be thoroughly evaluated to inform treatment decisions before they are made, Rizvi concludes. 

Naiyer A. Rizvi, MD, discusses treatment approaches in non–small cell lung cancer.

Dr. Rizvi on Utilizing Molecular Characteristics to Inform Treatment Decisions in NSCLC 

Naiyer A. Rizvi, MD, an associate attending physician, Memorial Sloan Kettering Cancer Center, discusses pembrolizumab (MK-3475) for the treatment of non-small cell lung cancer (NSCLC).

Rizvi says pembrolizumab is being explored in NSCLC in first-line and previously treated patients. The patients who express PD-L1 do very well on the agent, Rizvi says.

Pembrolizumab is also well tolerated in both first-line and pretreated NSCLC patients. The toxicity profile is favorable, Rizvi says, with low significant AE rates.

Dr. Rizvi Discusses Pembrolizumab for Non-Small Cell Lung Cancer

Naiyer A. Rizvi, MD, an associate attending physician, Memorial Sloan Kettering Cancer Center, discusses the safety and response seen with nivolumab plus erlotinib in patients with epidermal growth factor receptor mutant (

 MT) advanced non-small cell lung cancer (NSCLC).

 MT chemotherapy-naïve NSCLC patients received nivolumab 3 mg/kg IV Q2W plus erlotinib 150 mg PO daily until progression or unacceptable toxicity. The study showed that the combination was very tolerable and safe.

The data also showed a response rate of 19%, Rizvi says. The one patient enrolled in the study who was erlotinib naïve had a durable and deep response for the combination. Based on these results, Rizvi believes there is potential for the combination of checkpoint inhibitors, like nivolumab, with small molecule inhibitors in patients with 

View more from the 2014 ASCO Annual Meeting

Naiyer A. Rizvi, MD, an associate attending physician, Memorial Sloan Kettering Cancer Center, discusses the safety and response with plus erlotinib in patients with epidermal growth factor receptor mutant (EGFR MT) advanced non-small cell lung cancer (NSCLC).

Dr. Rizvi on Nivolumab Plus Erlotinib in Patients with EGFR MT NSCLC

Naiyer A. Rizvi, MD, an associate attending physician, Memorial Sloan-Kettering Cancer Center, discusses the phenomenon of pseudoprogression in patients with lung cancer after they receive immunotherapy treatment.

Rizvi says in a small number of patients that are treated with immunotherapy, early scans may show what looks to be signs of tumor growth. However, this may be a delayed benefit of the treatment or tumor inflammation as T cells become activated.

This phenomenon occurs in less than 10% of the patients, Rizvi says. Physicians should consider the patient’s well being in addition to scans in order to make a decision.

Dr. Rizvi on Pseudo-Progression in Lung Cancer

Naiyer A. Rizvi, MD, an associate attending physician, Memorial Sloan-Kettering Cancer Center, discusses PD-1 and PD-L1 antibodies in development for the treatment of lung cancer.

Rizvi says the anti-PD-1 antibodies nivolumab and MK-3475, and the anti-PD-L1 antibody MPDL3280A, are all being developed as treatments for stage IV lung cancer. Early studies of these agents have shown a response rate in the 20% range in patients with heavily pre-treated lung cancer who are resistant to chemotherapy and have failed all standard therapies. Rizvi says a 20% response rate is very encouraging for this group of patients.

Many of these patients have also showed durable responses, Rizvi says. Recently, the data from the nivolumab trial were updated to show a 2-year survival of 24%, which Rizvi says is a very high number for that patient population.

View coverage from the New York Lung Cancer Symposium

Naiyer A, Rizvi,MD

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