OBR Daily Commentary

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Pivotal Phase III Study Shows Roche’s Tecentriq Helped People With Early Lung Cancer Live Longer Without Their Disease Returning

(Roche) Mar 22, 2021 - Roche today announced that the Phase III IMpower010 study evaluating Tecentriq® (atezolizumab), compared with best supportive care (BSC), met its primary endpoint of disease-free survival (DFS) at the interim analysis. Tecentriq showed a statistically significant improvement in DFS as adjuvant therapy following surgery and chemotherapy in all randomised Stage II-IIIA populations with non-small cell lung cancer (NSCLC). The magnitude of DFS benefit was particularly pronounced in the PD-L1-positive population.

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H. Jack West, MD (Posted: March 22, 2021)

quotesThis is the first of likely several trials of adjuvant/neoadjuvant immunotherapy that will prove to be positive based on a surrogate endpoint, but here we have learned that it's especially favorable in those with PD-L1 positive cancers (which is the positive spin on "it was decidedly unimpressive in patients with PD-L1 negative cancers"), and with it reaching statistical significance for DFS on an interim analysis and no reported OS results, I suspect that we'll be left debating 1) whether statistical significance should imply clinical significance, 2) whether a DFS benefit that I'm going to predict is far less impressive than the HR of 0.17 seen for DFS on ADAURA should lead to a change in practice without seeing an improvement in OS, and 3) whether we should exclude patients who have PD-L1 <1% who (for the sake of argument I'll predict) show no meaningful improvement in DFS, let alone OS, with adjuvant atezolizumab. On top of this, we'll have room to debate whether FDA's shift to a mindset of providing the most liberal path to approval that can possibly be justified, not really filtering for clinically significant benefit, and then abrogating any responsibility for difficult judgment on appropriate use in practice to rank and file clinicians who won't have time or ability to focus on careful assessment of the data beyond being detailed by pharma reps. Also, we'll need to factor in not only the very significant financial cost of prolonged immunotherapy but the real risk of chronic, even permanent, treatment-induced toxicities from immunotherapy in patients who have a significant chance of already being cured from the treatments they'd have already received. I suspect that the results of this trial will compare unfavorably to the magnitude of benefit in terms of DFS that we saw with adjuvant osimertinib in the ADAURA trial, and this will lead to refinement of our question of how much we should focus on DFS and other surrogate endpoints like pathologic complete response rates as sufficient to change our practice, especially when "statistical significance" does not necessarily imply clinical significance.quotes

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U.S. FDA Expands Approval of Pfizer’s LORBRENA® as First-Line Treatment for ALK-Positive Metastatic Lung Cancer

(Pfizer) Mar 3, 2021 - The U.S. Food and Drug Administration (FDA) approved Pfizer Inc.’s supplemental New Drug Application (sNDA) for LORBRENA® (lorlatinib), expanding the indication to include first-line treatment of people with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). LORBRENA is now indicated for adults with metastatic NSCLC whose tumors are ALK-positive as detected by an FDA-approved test. The FDA action also converts the 2018 accelerated approval to full approval. The application was approved under the FDA’s Real-Time Oncology Review (RTOR) pilot program.

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H. Jack West, MD (Posted: March 05, 2021)

quotesLorlatinib is an excellent ALK inhibitor, but beating crizotinib as first line therapy for patients with ALK-positive advanced NSCLC only puts it on par with alectinib as a current standard of care or other 2nd generation ALK inhibitors also superior to crizotinib and approved in this setting. Lorlatinib has good activity, both extracranial and intracranial, but its toxicity profile is somewhat idiosyncratic, particularly the neuro-behavioral issues. I do not think it emerges as offering a clear incremental benefit over alectinib. Moreover, using lorlatinib first line means that it isn't available as second line therapy, where it is arguably the leading option after progression on alectinib or another ALK inhibitor. quotes

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FDA Approves Cemiplimab-rwlc For Non-Small Cell Lung Cancer With High PD-L1 Expression

(FDA.gov) Feb 22, 2021 - On February 22, 2021, the Food and Drug Administration approved cemiplimab-rwlc (Libtayo, Regeneron Pharmaceuticals, Inc.) for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) (locally advanced who are not candidates for surgical resection or definitive chemoradiation or metastatic) whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] > 50%) as determined by an FDA-approved test, with no EGFR, ALK or ROS1 aberrations. Efficacy was evaluated in Study 1624 (NCT03088540), a multi-center, randomized, open-label trial in 710 patients with locally advanced NSCLC who were not candidates for surgical resection or definitive chemoradiation or with metastatic NSCLC.

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H. Jack West, MD (Posted: February 23, 2021)

quotesThis approval now gives us a third option for the same clinical setting in which we already have pembrolizumab as a clear standard of care since it demonstrated significant superiority to chemotherapy alone in 2016. We also have atezolizumab that showed the same thing and currently serves as a rarely used understudy to pembrolizumab here, with no incremental benefit. Cemiplimab provides only further redundancy here. We should also reflect on the questionable ethics of running a trial that assigns half of the patients to a treatment that had been proven inferior to single agent immunotherapy from KEYNOTE-024 before the new trial started. Unfortunately, history has shown us that we should not expect the addition of more agents in the same setting to lead to improvements in pricing. I strongly suspect Regeneron will fail to price cemiplimab significantly lower than pembrolizumab or atezolizumab, which is the only factor that could differentiate it from better established competition in this market.quotes

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Meet the Editorial Board

Prostate Cancer
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Tomasz M. Beer, MD, FACP

Professor of Medicine, Division of Hematology/Medical O...

Community Oncology
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Dean Gesme, MD

FACP FACPE FASCO President, Minnesota Oncology...

Breast Cancer
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Debu Tripathy, MD

Professor and Chair, Department of Breast Medical Oncol...

Lung Cancer
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H. Jack West, MD

Associate Clinical Professor, Medical Oncology Executi...

Gastrointestinal Cancers
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Howard S. Hochster, MD

Distinguished Professor of Medicine, Rutgers Robert Woo...

Radiation Oncology
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Howard Sandler, MD, MS, FASTRO

Ronald H. Bloom Chair in Cancer Therapeutics Professo...

Editor-In-Chief
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Robert A. Figlin, MD., FACP

Steven Spielberg Family Chair in Hematology Oncology P...

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Stephen M. Schleicher, M.D., MBA

Community Oncology, Medical Oncologist, OneOncology...

Health Policy
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Ted Okon

Executive Director Community Oncology Alliance...

Community Oncology
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Thomas Marsland, MD

Vice President Integrated Community Oncology Network ...

Health Policy
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William McGivney, PhD

National Health Policy Expert...