The U.S. National Cancer Institute’s (NCI) PDQ Adult Treatment Editorial Board holds 6 in-person meetings a year in Rockville, Maryland. The Board, chaired by Franco Muggia of the New York University Medical Center, consists of approximately 25 cancer experts. Members who are not able to attend in person, because of schedule conflicts or distance, are able to attend meetings via audio- or videoconference. Board membership is primarily composed of medical oncologists, but also includes surgical and radiation oncologists. The Board has been meeting virtually since April of 2020 and will continue to do so until it is safe to meet in person, although some members will continue to join virtually after in-person meetings resume. The Board maintains approximately 70 cancer information treatment summaries, with each member assigned to cover summaries in his or her area of expertise. Members review recently published journal articles and decide if they should be added to a summary, then present the articles and suggested changes at a meeting. Changes are approved through a consensus process in which members evaluate the strength of the evidence in the published article to determine if it should be included in the summary. The Board met on 29 April 2021 and 15 June 2021 to review several articles and summaries. Although discussions were led by individuals, the final decisions to include the articles and text were approved by the whole Board. Some of these changes have not yet been made to the summaries and are expected to be posted on Cancer.gov in the following weeks.
• Esophageal Cancer Treatment: Our newest Board member, Andrea Bonetti of Verona, joined us for the second time and presented two recent journal articles and edits to the Esophageal Cancer Treatment summary.
Kelly RJ, Ajani JA, Kuzdal J, et al.: Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. New England Journal of Medicine 384(13): 1191-1203, 2021.
Editorial: Ilson DH: Adjuvant nivolumab in esophageal cancer—a new standard of care. New England Journal of Medicine 384(13): 1269-1271, 2021.
Smyth EC, Gambardella V, Cervantes A, et al.: Checkpoint inhibitors for gastroesophageal cancers: dissecting heterogeneity to better understand their role in first-line and adjuvant therapy. Annals of Oncology 32(5): 590-599, 2021.
• General Treatment: The Board reviewed two papers that underscored the possible influential role of financial payments from the pharmaceutical industry to prescribing physicians, the increasing role of industry sponsorship in modern trials, and the increasing use of professional writers in writing the manuscripts. (The role of medical writers was also recently underscored in an editorial by Ian Tannock published in Annals of Oncology 32:437-8 entitled “Have investigators forgotten how to write?”)
Mitchell AP, Trivedi NU, Gennarelli RL, et al.: Are financial payments from the pharmaceutical industry associated with physician prescribing? A systematic review. Annals of Internal Medicine 174: 353-361, 2021.
Del Paggio JC, Berry JS, Hopman WM, et al.: Evolution of the randomized clinical trial in the era of precision oncology. JAMA Oncology E1-E7, 2021.
• Small Cell Lung Cancer Treatment: The Recurrent Treatment section was updated to reflect withdrawal of approval for KEYNOTE-604 use of pembrolizumab + platinum/etoposide since it failed to meet primary endpoint of overall survival (OS) –whereas two PD-L1 check point inhibitors did meet OS advantage over placebo.
• Plasma Cell Neoplasms Treatment: The Perrot et al. paper introduced the advantages of daratumubab (D) added to lenalidomide and dexamethasone (Rd) v Rd alone. It introduced the activity of the proteasome inhibitor ixazomib as maintenance for multiple myeloma (MM) patients not able to tolerate lenalidomide maintenance. Daratumumab also added to the results of carfilzomib + dexamethasone in pretreated MM patients. In the BELLINI trial, venetoclax was added to bortezomib and dexamethasone as an active drug for MM patients. Finally, text was added on the efficacy in applying the bortezomib, melphalan, and dexamethasone regimen for light chain amyloidosis.
Perrot A, Facon T, Plesner T, et al.: Health-Related Quality of Life in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: Findings From the Phase III MAIA Trial. Journal of Clinical Oncology 39 (3): 227-237, 2021. PMID: 33326255
Dimopoulos MA, Špička I, Quach H, et al.: Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial. J Clin Oncol 38 (34): 4030-4041, 2020. PMID: 33021870
Gavriatopoulou M, Chari A, Chen C, et al.: Integrated safety profile of selinexor in multiple myeloma: experience from 437 patients enrolled in clinical trials. Leukemia 34 (9): 2430-2440, 2020. PMID: 32094461
Kumar SK, Harrison SJ, Cavo M, et al.: Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncology 21 (12): 1630-1642, 2020. PMID: 33129376
Kastritis E, Leleu X, Arnulf B, et al.: Bortezomib, Melphalan, and Dexamethasone for Light-Chain Amyloidosis. J Clin Oncol 38 (28): 3252-3260, 2020. PMID: 32730181
• Nasopharyngeal Carcinoma Treatment: This summary was extensively revised and new formatting has been added to make the summary more user-friendly. Among the many changes, mention of a salted fish diet as a risk factor was removed, and text was added on induction gemcitabine/cisplatin chemotherapy prior to chemoradiation v just chemoradiation.
Wang Q, Xu G, Xia Y, et al.: Comparison of induction chemotherapy plus concurrent chemoradiotherapy and induction chemotherapy plus radiotherapy in locally advanced nasopharyngeal carcinoma. Oral Oncol 111: 104925, 2020. PMID: 32721816
• Adult Soft Tissue Sarcoma Treatment: This summary was extensively revised and new formatting has been added to make the summary more user-friendly. Molecular biology is leading the changes in this area, with the PDQ Pediatric Treatment Editorial Board already revising their summary for children. Many patients with Li-Fraumeni, neurofibromatosis Type 1, Gardner syndrome, nevoid basal cell or Gorlin syndrome, Tuberous sclerosis and Werner syndrome are linked with germline mutations of TP53, NF1, APC, PTCH1, TSC1 or TSC2, and WRN, respectively. The diagnostic evaluation in adult sarcomas has evolved by including radiation and surgical oncologists and interventional radiologists in the local planning and assessment of metastatic sites. PET/CT scans are particularly useful in the few subtypes with a propensity to seed nodal areas. This summary links with other PDQ summaries, including Childhood Soft Tissue Sarcoma Treatment, Gastrointestinal Stromal Tumors Treatment, Kaposi Sarcoma Treatment, and Uterine Sarcoma Treatment. In the real clinical example of a teenager with an alveolar soft-part sarcoma and brain metastases, the Childhood Soft Tissue Sarcoma Treatment summary had much complementary information.
Our June meeting included noteworthy presentations from the recent (virtual) ASCO meeting. While the Board generally prefers to wait for studies presented at ASCO to be available as full publications, they do occasionally decide to cite abstracts (and note in the text that the report is in abstract form), especially when the drug(s) studied are widely available for use by oncology practitioners.
• Esophageal Cancer Treatment: Andrea Bonetti described the plenary session presentation by Chau et al. CheckMate 648 used nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy as a first-line treatment for advanced esophageal squamous cell carcinoma (ESCC) and showed a PFS of 10.7 v 13.2m with the anti PD1 every 3 weeks. Another abstract from Xu et al. in the same population, also a positive study, compared camrelizumab + chemotherapy v chemotherapy alone. The Board decided to await full publication of the second abstract to include these results in the summary because U.S. oncologists would not be able to obtain this antibody.
Chau I, Doki Y, Ajani JA, et al.: Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) v chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): first-results of the CheckMate 648 study. Journal of Clinical Oncology 39 (suppl 15, LBA4001), 2021.
Xu, Luo H, Lu J, et al.: ESCORT-1st: A randomized, double-blind, placebo-controlled, phase 3 trial of camrelizumab plus chemotherapy v chemotherapy in patients with untreated advanced or metastatic esophageal squamous cell carcinoma (ESCC). Journal of Clinical Oncology 39 (suppl 15, A-4000), 2021.
• Nasopharyngeal Cancer Treatment: Andrea Bonetti also reviewed the JUPITER-02 trial, which compared gemcitabine and cisplatin with toripalimib plus gemcitabine and cisplatin, and corresponding revisions to the summary. This IgG4 antiPD1 compound improved PFS from 6m to 11.7m and OS also diverged at 2 years favoring the addition of the antibody.
Xu Rh, Mai HQ, Chen QY, et al.: JUPITER-02: Randomized, double-blind, phase III study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC). Journal of Clinical Oncology 39 (suppl 15, LBA2), 2021.
• Prostate Cancer Treatment: Two published trials, both by Fizazi et al. (NEJM 2019 and NEJM 2020), dealt with the introduction of the 4th powerful hormonal manipulation after abiratorone and 3rd androgen receptor (AR) antagonist after enzalutamide, apalutamide, and now darolutamide that has less CNS penetrance and perhaps better tolerance. A paper from Hussain et al. provided an update on olaparib after castrate-resistant disease progression prior to any chemotherapy and with at least an alteration in BRCA1, BRCA2 or ATM. In this phase III study OS was 19.1m v 4.7m with placebo. The Board approved updates to the summary describing these studies.
Fizazi K, Shore N, Tammela TL, et al.: Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. New England Journal of Medicine 380 (13): 1235-1246, 2019. PMID: 30763142
Fizazi K, Shore N, Tammela TL, et al.: Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. New England Journal of Medicine 383 (11): 1040-1049, 2020. PMID: 32905676
Hussain M, Mateo J, Fizazi K, et al.: Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. New England Journal of Medicine 383 (24): 2345-2357, 2020. PMID:32955174
• Bladder Cancer Treatment: The role of immune check point inhibitors—in this instance, avelumab maintenance in advanced urethelial carcinoma v best supportive care—was updated. The results in 700 randomized patients favored avelumab (5.7m v 2.1m).
Powles T, Park SH, Voog E, et al.: Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. New England Journal of Medicine 383 (13): 1218-1230, 2020. PMID: 32945632
• Melanoma Treatment: The stage III melanoma treatment section was updated with data from a double-blind study of adjuvant pembrolizumab v placebo in 1019 patients accrued from April 2015 to November 2016. Hazard rates (HR) were 0.59 (95%CI .49-.70) for recurrence and HR were .44 (95% CI .39-.49) for the 853 patients who had PD-L1-positve tumors.
Eggermont AMM, Blank CU, Mandalá M, et al.: Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncology 22: 634-654, 2021.
• Bile Duct Cancer Treatment: This is a somewhat new area for cancer therapeutics, with a study of FOLFOX v symptomatic control for an open-labeled randomized trial in second line treatment. The results were compelling, with an improved survival with FOLFOX (median 6.2m v 5..3m for active supportive care alone). At 1 year, 25.9% of patients assigned to FOLFOX were alive v 11.4% of patients on supportive care. These cancers have shown responses to FGFR-selective tysrosine kinase inhibition: infigratinib has received accelerated FDA approval based on a phase II study in previously treated patients. The presentation at ASCO provided the data on 108 patients who had progressed after at least one line of chemotherapy –all patients received the drug orally once daily for 21 days and resumed after a 7-day break. Responses were seen in 25 patients, and 8 had lasting responses beyond 6m. The most common toxicities were low phosphate (76.9%) and stomatitis in slightly more than half of patients. Fatigue was prominent in 40% of patients. Of additional concern were serous retinal changes, with at least one grade 3 event and retinal detachment in 16.7% of patients. The Board approved updates to the summary describing these studies.
Lamarca A, Palmer DH, Wasan HS, et al.: Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol 22 (5): 690-701, 2021. PMID: 33798493
Javle M, Roychowdhury S, Kelley RK, et al.: Final results from a phase II study of infigratinib (BGJ398), an FGFR-selective tyrosine kinase inhibitor, in patients with previously treated advanced cholangiocarcinoma harboring an FGFR2 gene fusion or rearrangement. [Abstract] J Clin Oncol 39 (3) (suppl): A-265, 2021. Available online. Last accessed June 8, 2021.
• Breast Cancer Treatment: The TRAIN-2 study was discussed, and prominent mention was made of the OlympiA study, which was presented at the ASCO plenary session and established olaparib’s impact on early-stage breast cancer v placebo when given as maintenance after primary therapy. The full publication is awaited before amending the PDQ summary. Male Breast Cancer Treatment is undergoing a major revision to incorporate some of the advances that have been added in the more comprehensive breast cancer summary.
Van Ramshorst MS, van der Voort A, van Werkhoven ED, et al.: Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phased 3 trial. Lancet Oncology (19): 1630-1640, 2018. PMID: 30413379
• Ovarian Epithelial, Primary Peritoneal, and Fallopian Tube Cancer Treatment: This summary was updated by Franco Muggia of NYU with the discussion of several articles relating to PARP inhibitors. Tables are underway to best display the various trial results as they have transitioned from use after 3 to 5 lines of therapy in women with BRCA mutations to their current use in early disease given orally as maintenance. In all of these trials hazard ratios significantly favor these drugs v placebo, with the results being more prominent in germline BRCA carriers. Additional updates on low grade serous tumors, which were treated quite differently during the past two decades, are expected soon as well.
Poveda A, Floquet A, Ledermann JA, et al.: Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-OV21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncology 22: 620-631, 2021.
Friedlander M, Moore KN, Colombo N, et al.: Patient-centered outcomes and effect of disease progression on health status in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation receiving maintenance Olaparib or placebo (SOLO1): a randomised, phase 3 trial. Lancet Oncology 22: 632-642, 2021.
Stay tuned for more PDQ changes.